7/29/2019 Tutorial-C21-0110.pdf

1/56

1

COSMOtherm

XA Graphical User Interface tothe COSMO therm Program

Tutorial for version C21_0110

November 27th

2009

COSMOlogic GmbH & Co. KGBurscheider Str. 515, D-51381 Leverkusen, Germany

7/29/2019 Tutorial-C21-0110.pdf

2/56

7/29/2019 Tutorial-C21-0110.pdf

3/56

3

4.16 Viscosity ....................................................................................................................................... 44 4.17 The -moment approach and QSPR calculations ..................................................................... 44 4.18 Similarity ..................................................................................................................................... 46 4.19 Liquid extraction ........................................................................................................................ 47 4.20 Reaction ...................................................................................................................................... 48

Example: Solvent choice for a simple ester reaction ............................................................... 49 5 Using your own COSMO files ............................................................................................................ 50

5.1 Using the file manager .............................................................................................................. 50 5.2 Adding your own databases ...................................................................................................... 50 5.3 Extend the existing databases ................................................................................................... 51

6 Atom weighting ................................................................................................................................. 52

Index ........................................................................................................................................................... 54

7/29/2019 Tutorial-C21-0110.pdf

4/56

4

Abbreviations

2D: Two dimensional3D: Three dimensional

AM1: A semiempirical quantum chemical methodsBP-SVP / BP-TZVP: Becke-Perdew1, 2, 3 (BP) functional for density functional theory calculations

with a single valence plus polarization function (SVP) or triple valence pluspolarization function basis set. The necessary parameterization file doesalways correspond to one functional and basis set. The term BP-TZVPparameterization is thus sometimes used and refers to the COSMO therm parameterization not the basis set specification.

CAS-Number: The Chemical Abstracts Services registration number is a unique identifierfor compounds.

COSMO: COnductor like Screening ModelCOSMO-RS: Conductor like Screening Model for Real SolventsDB: Database, usually used for the COSMO therm compound databases.DFT: Density Functional Theory: A quantum chemical theory used in several

software packages for molecular or lattice calculations.HB: Hydrogen BondLFER: Linear Free Energy RelationshipLLE: Liquid Liquid EquilibriumMW: Molar WeightQC / QM: Quantum Chemical / Quantum MechanicalQSPR: Quantitaive Structure Property Relationship, also QSAR (A = activity)

(sigma): The COSMO screening charge

SLE: Solid Liquid EquilibriumSMILES: Simplified Molecular Input Line Entry Specification, notation to describe

molecules e.g. methane is C ethane is CC and ethanol is CCO SMS: Sigma Match SimilarityVLE: Vapor Liquid Equilibrium

7/29/2019 Tutorial-C21-0110.pdf

5/56

5

HO

H

HO

H OC

O

HO

HHO

H

HO

H

HO

OH H

O

HO

H

H

HO

H

HO

H OC

O

HO

HHO

H

HO

H

HO

OH H

O

HO

H

H

1 Introduction: COSMO-RS theory

COSMO-RS is a predictive method for thermodynamic equilibria of fluids and liquid mixtures thatuses a statistical thermodynamics approach based on the results of quantum chemical calculations.

The underlying quantum chemical model, the so called COnductor -like Screening MOdel (COSMO)4, is an efficient variant of dielectric continuum solvation methods. In COSMO calculationsthe solute molecules are calculated in a virtual conductor environment. In such an environment thesolute molecule induces a polarization charge density on the interface between the molecule andthe conductor, i.e. on the molecular surface. These charges act back on the solute and generate amore polarized electron density than in vacuum. During the quantum chemical (QC) self-consistencyalgorithm, the solute molecule is thus converged to its energetically optimal state in a conductorwith respect to electron density. The molecular geometry can be optimized using the same methodsfor calculations in vacuum. The time consuming QC calculation has to be performed only once foreach molecule of interest.The polarization charge density of the COSMO calculation (also called screening charge density),which is a good local descriptor of the molecular surface polarity, is used to extent the modeltowards Real Solvents (COSMO -RS)5, 6 . The (3D) polarization density distribution on the surface ofeach molecule i is converted into a distribution-function, the so called -profile p i ( ), which givesthe relative amount of surface with polarity on the surface of the molecule. The -profile for theentire solvent of interest S , which might be a mixture of several compounds, p S ( ) can be built byadding the p i ( ) of the components weighted by their mole fraction x i in the mixture.

Si

iiS p x p (1)

The most important molecular interaction energy modes, i.e. electrostatics ( E misfit ) and hydrogenbonding ( E HB) are described as functions of the polarization charges of two interacting surfacesegments and ' or acceptor and donor , if the segments are located on a hydrogen bond donor oracceptor atom. Electrostatic energy arises from the misfit of screening charge densities and ', as

illustrated above. The less specific van der Waals ( E vdW ) interactions are taken into account in aslightly more approximate way.

2)'(2')',( eff misfit a E (2)

7/29/2019 Tutorial-C21-0110.pdf

6/56

6

HBacceptor HBdonor HBeff HB ;;;ca E 000 maxminmin (3)

vdW vdW eff vdW a E ' (4)

Eqs. 2-4 contain five adjustable parameters, an interaction parameter , the effective contact areaa eff , the hydrogen bond strength c HB, the threshold for hydrogen bonding HB, and the elementspecific vdW interaction parameter vdW . In order to take the temperature dependency of E HB andE vdW into account, temperature dependent factors are applied, each with one adjustableparameter. 7 The transition from microscopic molecular surface charge interactions to macroscopicthermodynamic properties of mixtures is possible with a statistical thermodynamic procedure. Themolecular interactions in the solvent are fully described by p S ( ), and the chemical potential of thesurface segments can be calculated solving a coupled set of non-linear equations.

'd',','exp'ln HBmisfit S

eff

Seff

S E E RT

a

pa RT

(5)

The -potential S ( ) is a measure for the affinity of the system S to a surface of polarity . The vdWenergy, which does not appear in Eq. (5), is added to the reference energy in solution (energy ofthe COSMO calculation). The chemical potential of compound i in the system S (the solvent) cannow be calculated by integration of S ( ) over the surface of the compound.

d, Sii SC iS p (6)

To take into account size and shape differences of the molecules in the system an additionalcombinatorial term, i C,S , which depends on the area and volume of all compounds in the mixtureand three adjustable parameters is added. For information on the exact expression for thecombinatorial term refer to the COSMO therm Users Manual. The chemical potential can be used tocalculate a wide variety of thermodynamic properties, e.g. the activity coefficient:

RT

ii

iSi

S

exp (7)

where i S is the chemical potential in the solvent S , and i i is the chemical potential of the purecompound i .For a more detailed introduction to COSMO and COSMO-RS, refer to the COSMO therm UsersManual and the cited literature.

7/29/2019 Tutorial-C21-0110.pdf

7/56

7

2 COSMO therm and COSMO therm X

COSMOtherm is a command line/file driven program which can be run directly from a UNIX or DOSshell. It allows for the calculation of any solvent or solvent mixture and solute or solute system at

variable temperature and pressure. COSMO therm uses the chemical potentials derived fromCOSMO-RS theory to compute all kinds of equilibrium thermodynamic properties or derivedquantities, e.g.:

Vapor pressure Free energy of solvation Activity coefficients Partition coefficients Solubility and solid-liquid equilibria (SLE). Liquid-liquid equilibrium (LLE) and vapor-liquid equilibrium (VLE)

Phase diagrams, azeotropes, miscibility gaps, excess enthalpies and excess free energies pKA of acids and bases Various QSPR models Reaction constants Liquid extraction equilibria

COSMOtherm X is a Graphical User Interface to the COSMO therm command line program. It allowsfor the interactive use of the COSMO therm program, i.e. selection of compounds, preparation ofproperty input, program runs and display of calculation results.

2.1 Quality levels and parameterizationsThe input for the compounds is read from the COSMO files, identified by the extensions .cosmo or.ccf , which are result files from quantum chemical COSMO calculations. COSMO therm extracts therelevant information directly from the COSMO files. The compressed COSMO files (.ccf ) usesignificantly less disk space than conventional COSMO files. At least one COSMO file or compressedCOSMO file has to be selected as compound input.Because the quality, accuracy, and systematic errors of the electrostatics resulting from theunderlying COSMO calculations depend on the quantum chemical method as well as on the basisset, COSMO therm needs a special parameterization for each method / basis set combination. All ofthese parameterizations are based on molecular structures quantum chemically optimized at thegiven method / basis set level.COSMO files shipped with COSMO therm are available on various quantum chemical levels.Recommendations for which method to use depend upon the required quality and the later usageof the predictions.The application of COSMO therm in chemical and engineering thermodynamics (e.g. prediction ofbinary VLE or LLE data, activity coefficients in solution or vapor pressures) typically requires highquality of property predictions of mixtures of small to medium sized molecules (up to 25 non-Hydrogen atoms). The recommended quantum chemical method for such a problem is a fullTURBOMOLE BP-RI-DFT COSMO optimization of the molecular structure using the large TZVP basisset 8, in the following denoted BP-TZVP, and the corresponding parameter fileBP_TZVP_C21_0110.ctd . A similar quality can be reached with the DMOL3 program package

using full COSMO and gas phase geometry optimization with the PBE DFT functional and thenumerical DNP basis set and the corresponding parameter file DMOL3_PBE_C21_0110.ctd inCOSMOtherm .

7/29/2019 Tutorial-C21-0110.pdf

8/56

8

As an alternative approach for predictions in the core region of fluid-phase organic chemistry thecalculation level BP-TZVP-ISOCAV was introduced to COSMO therm and TURBOMOLE in 2008. Thismethod is based on a full Turbomole BP-RI-DFT COSMO optimization of the molecules geometryusing the large TZVP basis set, and on top of the optimized BP/TZVP/COSMO geometry, employs anovel type of molecular surface cavity construction (Scaled Isodensity Surface), based on the

electron density distribution of the molecule. Until further experience is gained, this level of theoryand parameterization are provided in an as is state.

Screening a large number of compounds, e.g. prediction of solubility of compounds in varioussolvents, typically requires a predictive quality that is somewhat lower than for chemicalengineering applications. The molecules involved are often larger (>100 atoms) and an overall largenumber of compounds has to be computed by quantum chemistry. Thus a compromise betweencomputational demands and quality of the predictions has to be made: A very good compromise isthe optimization of molecular geometry on the computationally very cheap semiempirical MOPACAM1-COSMO level 9 with a subsequent single point COSMO calculation on Turbomole BP-RI-DFTCOSMO level using the small SVP basis set. This method is named BP-SVP-AM1 in the following, andthe corresponding parameterization is available in the BP_SVP_AM1_C21_0110.ctd parameterfile.For more information on available quantum chemical levels and parameterizations refer to theCOSMOtherm Users Manual, section 3 .

2.2 Getting startedAt initial start of COSMO therm X a GENERALSETTINGS dialog opens where some settingsare already specified: Paths for theCOSMOtherm executable and the CTDATA

directory of the COSMO therm installationare set, and the parameter files for thequantum chemical levels (extension .ctd )are specified. Additionally, you can set pathsfor the Adobe Acrobat Reader and a webbrowser. If you intend to use COSMOmetafiles (extension .mcos ) for thefragment approach, you should also specifythe fragment directory. When the path forthe QSPR property directory is set QSPRcoefficient files (extension

.prop) can be read from there.

A standard user directory can be specified, which will automatically be used after COSMO therm X isstarted. If you want to save input file the user directory will be used as starting point for the fileselect dialog. After saving a file, the last used directory will be used as long as COSMO therm X is notclosed.Similar to the standard user directory a standard data directory can be defined. This directory willbe used for the CONVERT SELECTIONoption form the compound list context menu.USE NETBOOK OPTION(SCROLLBARS) will enable global scrollbar for the main window. This is helpful forsmall displays.

The databases that come with

the COSMO therm release arespecified in the D ATABASES panel. Additional databases

7/29/2019 Tutorial-C21-0110.pdf

9/56

9

can be added in this panel with ADD DATABASES. For detailed information on adding your owndatabases, refer to the section Using your own COSMO files. The G ENERALSETTINGScan always be changed in the E XTRA / GENERALSETTINGSmenu. Changes can bedone permanently or for the current session only, e.g. in order to use a special parameterization.

2.3 Flowchart of a property calculation with COSMO therm X

Start

Select compounds from theDatabases or the File

Manager

Found allcompounds?

Yes

No

Select settings for propertycalculations

Use the Compound Wizard togenerate COSMO files and/or

gas phase structures.

Add compounds to database

Add

Another

property?

Run

Yes

No

COSMOtherm X external

TURBOMOLE

7/29/2019 Tutorial-C21-0110.pdf

10/56

10

2.4 The main windowThe main window is separated into 4 parts: the pull down menu and shortcuts section in the upperregion, the compounds list, database access and file list on the left side, the input preparation andthe property section on the right and right bottom side.

The COSMO therm X main window has several menus:File:NEW: Create a new input file. Type the filename and press Open. Also available as shortcut .

OPEN: Open an existing input file. Select a file from the directory or type the filename into the Filena me text field and press Open. The panel also allows for changing the directory, also availableas shortcut .

OPEN SCREENINGFILE: Allows to open an existing solvent screening file. The solvent screening is acomplex option and a special format is thus needed.

OPEN COMPOUND LIST: A list of previously saved compounds can be loaded with this option. The saved

concentrations of the compounds will also be loaded but not automatically applied. Please selectAPPLYLISTCONCENTRATIONSfrom the extras menu for this feature.

SAVE: Save the input file to the current directory with the actual name. Also available as shortcut .

SAVE AS: Choose a directory and a name for the input file to be saved.Open Table File: Select a COSMO therm table file from the directory or type the filename into theFile name text field and press Open. The panel also allows for changing the directory.

SAVE COMPOUND LIST: With this option it is possible to save the complete compound list to a file forlater use. The concentrations are also saved. To save only the selected compounds to a list the SAVETO COMPOUND LISToption from the compound list context menu has to be used.

OPEN MIC FILE: Open an output file from a COSMO mic run.

Main menu and shortcuts

Compound listFilesDatabase access

Input preparation

Property section

7/29/2019 Tutorial-C21-0110.pdf

11/56

11

VIEW VRMLIN BROWSER: Open an existing .wrl file in a web browser window. A VRML browser plug-in has to be installed and the path of the browser has to be given in the G ENERALSETTINGSdialog.

QUIT: Exit the program.

Run:RUN: The actual input file is saved automatically with the current file name and COSMO therm is run.Also available as shortcut .

EDIT INPUT: Open the actual input file in a text editor window. The input file can be changedmanually, e.g. for additional input in the compound lines (further information: COSMO therm UsersManual). Then, the input file can be saved or COSMO therm can be run. Note that not all changescan be read in when the input file is re-opened with COSMO therm X. Also available as shortcut .

RUN (EXTERNAL) INPUT: A COSMOtherm calculation can be run with an external input file, withoutopening it in the GUI. Any valid COSMO therm input file can be run.

Extras:GLOBAL OPTIONS: A panel with selections for gas phase energy input, units, COSMO therm outputprint options, additional output files and program control. Also available as shortcut . For adetailed description of the global options dialog see below.

MIXTUREOPTIONS: A panel with options applying to settings for the mixture calculation. A shortcut isalso available in the main window. Mixture options are used to apply certain options to a mixtureonly. With this options it is possible to use different options in a single COSMO therm run. Mixtureoptions will only be used if the Use Mixture Options checkbox is activated in the property panel.If several mixtures or properties are calculated in a single run, the mixture options have to beactivated each time the property settings are transferred the property selection window, otherwisethey will not be used for the respective property calculation. For a detailed description of themixture options dialog see below.

APPLY LIST CONCENTRATIONS: If a list of molecules is saved from the compound context menu, thecomposition is also saved. To app ly these compositions, it is necessary to chose the Option ApplyList Concentrations from the extras menu. These concentrations are not automatically applied,when the list is loaded!

VIEWERSETTINGS: Change atom / bond color, show or hide label, change sphere / cylinder smoothnessand so on.

GENERALSETTINGS: Opens the G ENERALSETTINGSdialog where the COSMO therm executable path andother settings can be changed. This is the same dialog that pops up at initial use.

Tools:VRML-VIEWER: Opens the COSMO view tool which allows for the visualization of .wrl filesgenerated by COSMO therm . For more information, please refer to the section UsingCOSMOview .

METAFILE-EDITOR: Opens the COSMO weight tool. For information on atom weighting and theCOSMOweight tool, please refer to the section Atom Weighting.

7/29/2019 Tutorial-C21-0110.pdf

12/56

12

Databases:SVP DB: open database index files of the BP-SVP-AM1 level of theory in tabulated form.

TZVP DB: open database index files of the BP-TZVP level of theory in tabulated form.

ISOCAV DB: open database index files of the BP-TZVP-ISOCAV level of theory in tabulated form.

DMOL3 DB: open database index files of the DMOL3-PBE level of theory in tabulated form.

SEARCH IN ALLDB: Search a compound in all databases that are listed in the E XTRAS / GENERALSETTINGS DATABASESpane, irrespective of the parameterization which the DBs are linked to.

COMPOUND WIZARD: The Compound Wizard allows searching for a compound by name, CAS-Number,SMILES or structure. It also offers the possibility to generate a complete new structure withTURBOMOLE (if installed).

FILEMANAGER: Opens a compound from an arbitrary directory.

Help:PHYSICALCONSTANTS: Displays information about some physical constants and conversion factors.

COSMOTHERMMANUAL: Open the COSMO therm Users Manual with the Adobe Acrobat Reader.

COSMOTHERMX TUTORIAL: Open the COSMO therm X Tutorial (this document) with the Adobe AcrobatReader.

COSMOMIC MANUAL: Open the COSMO mic manual with the Adobe Acrobat Reader.

ABOUT: Information about the current COSMO therm X version is displayed.

2.5 Global optionsGlobal options can be set from the GLOBAL OPTIONS panel. The panel offers selectio ns for gasphase energy input, units, COSMO therm output print options, additional output files, programcontrol and QSPR options . The panel can be opened from Extras /Global Options or directly fromthe main window.Global options apply for the whole COSMO therm run, i.e. all temperature / mixture / property linesin the input.

Gas phase estimation:USE ENERGY FILE: The gas phase energy is required for certain properties (e.g. the calculation of thechemical potential in the gas phase). It can be taken from a gas phase quantum chemicalcalculation ( .energy file) or empirically estimated by COSMO therm . If possible, the quantumchemical calculated value of the gas phase energy should be used. Energy files from COSMO base use Hartree units. If this option is checked COSMO therm will use the energy file if no adequatepure compound properties are available.

USE COMPOUND PROPERTY FILE: For some properties experimental vapor pressure data can be used. Therelevant pure compound property data are taken from the .vap file. The Antoine or Wagnercoefficients might be used in this case.

7/29/2019 Tutorial-C21-0110.pdf

13/56

13

Units: The units for the gas phase energy input and the general COSMO therm output of the calculatedproperties can be chosen here.

Print options for the COSMO output file:PRINT COMPOUND / MIXTURE NUMBER: Write compound / mixture number to the right side of the outputfile. This may be useful for efficient processing of the output file.

PRINT CONFORMER INFO: If a compound input consists of several conformers this option causes theoutput of the calculated COSMO therm mixture information to be written for each individualconformer. By default, only the results for the mixed compound are written to the output file.

SUPPRESS PURE COMPOUNDS INFO: Pure compound information will not be written to the output file.

SUPPRESS MIXTURE OUTPUT IN.OUT FILE: Mixture information will not be written to the output file.

PRINT15 DIGIT LONG NUMBERS TO.OUT-FILE: Print all real numbers in scientific exponent number formatwith 15 significant digits to the output file

PRINT FULL LENGTH ATOMIC WEIGHT STRING: Print complete atomic weight or real weight string to thecompound section of the output file. If you toggle this option, the line for the atomic weights maybecome very long.

PRINT MOLECULAR SURFACE CONTACTS: Print statistics of molecular surface contacts for all compounds inall mixtures to the output file. For a detailed description see section 5.7 of the COSMO therm Users

Manual.

PRINT DETAILED SEGMENT MOLECULE CONTACTS: Print statistics of the molecular surface contacts for allsegments of all compounds in all mixtures to the output file and to the contact statistics table filename.contact . Refer to the COSMO therm Users Manual, section 5.7, for details.

PRINT DERIVATIVES OF CHEMICAL POTENTIAL: Print the values of the temperature and compositionderivatives of the chemical potentials of all compounds in all mixtures to the output file. Seesection 5.6 Chemical Potential Gradients of the COSMOtherm Users Manual for furtherinformation.

Additional output files:-MOMENTS (.MOM): Write the -moments of all processed compounds in tabulated form to

filename.mom . In addition some other molecular information will be written to filename.mom ,including volume V, molecular weight, dielectric energy E diel , average energy correction dE, van derWaals energy in continuum E vdw , ring correction energy E ring and the standard chemical potential ofthe molecule in the gas phase with respect to the ideally screened state QSPRgas = ECOSMO - Egas + dE +EvdW + Ering gas RT, using T = 25C. Please note that QSPRgas is only used as special QSPR descriptorand is only loosely connected to the gas phase chemical potential used otherwise). Refer also tosections 5.4 and 5.5 of the COSMO therm Users Manual.

ATOMIC -MOMENTS (.MOMA): Write the atomic -moments of all processed compounds tofilename.moma . If this option is used, -moments will be calculated for each atom of thecompounds.

7/29/2019 Tutorial-C21-0110.pdf

14/56

14

-PROFILES(.PRF): Write the -profiles of all processed compounds to file filename.prf . A summaryof the -profiles will be written in tabulated form to the table file filename.tab .

-POTENTIALS(.POT): Write the -potentials of all calculated mixtures to filename.pot . A summaryof the -potential information will be written in tabulated form to the table file filename.tab .

GENERATE VRML (GEOMETRY): Create VRML files name_mol.wrl of the molecular geometry of allcompounds. The files will be written to the directory of the selected input file in the nextCOSMOtherm run.

GENERATE VRML ( -SURFACE): Create VRML files name_sig.wrl of the molecular COSMO surfacecharges of all compounds. The files will be written to the directory of the selected input file in thenext COSMO therm run.

QSPR Property Computation: Only one of the following options can be chosen at a time. These options allow for the calculation

of special properties in addition to normal COSMO therm calculations. If different QSPR propertiesshould be calculated in a single run, the M IXQSPR panel has to be used.Please be aware, that the fitting for QSPR is done on the BP-SVP-AM1 parameterization level. Onlycompounds from the SVP Database should be used.NO SELECTION: This option is preselected, no QSPR (Quantitative Structure Property Relationship) willbe calculated.

LOGBB.PROP: The penetration of the blood brain barrier will be calculated.

LOGKIA.PROP: The intestinal absorption will be calculated.

LOGKHSA.PROP: The binding to human serum albumin will be calculated.

LOGKOC.PROP: The soil water partition will be calculated.

LOGPOW. PROP: The octanole water partition will be calculated.

By default, the computed property value will be listed in the compound section of theCOSMOtherm output file. An additional file with the extension .mom will be written, listing themolecular -moments and, in the last column, the computed property. Note that QSPR propertycalculations can also be done from the Mix-QSPR card, which allows for a larger variety of settings.

Program control settings: SWITCH OFF TEMP. DEPENDENCY OF HYDROGEN BOND CONTRIB.: Switch off temperature dependency of the

VRML, the "Virtual Reality Modeling Language, is a script language allowing for theinteractive examination of virtual three-dimensional objects. VRML files are usuallyidentified by the extension .wrl. All VRML files generated by COSMO therm can beviewed by the internal VRML viewer of COSMO therm .Otherwise, VRML files can be viewed with common World-Wide-Web browsers such asMozilla Firefox or Microsoft Internet Explorer if an appropriate VRML browser plug-inhas been installed. Plug-ins are freely available, e.g. the Cortona VRML client

http://www.parallelgraphics.com/products/cortona

7/29/2019 Tutorial-C21-0110.pdf

15/56

15

hydrogen bond contribution to the total interaction energy of the compound for the completeCOSMOtherm run.

SWITCH OFF TEMP. DEPENDENCY OF VAN DERWAALS CONTRIB.: Switch off temperature dependency of thevan der Waals contribution to the total interaction energy of the compound, active for the

complete COSMO therm run.

SWITCH OF HYDROGEN BONDING: Switch off hydrogen bonding (HB) contribution to the chemicalpotential.

SWITCH OFF VAN DER WAALS CONTRIBUTIONS: Switch off van der Waals (vdW) interaction energycontribution to the chemical potential.

SWITCH OFF COMBINATORIAL CONTRIB. TO CHEMICAL POTENTIAL: Switch off combinatorial contribution to thechemical potential for the complete COSMO therm run.

USE SUM OF FRAGMENT ENERGIES AS METAFILE ENERGY: (Expert use only) Use the sum of the fragmentCOSMO file energies in the calculation of the total free energy (by default a zero value is usedinstead). Details on the usage of atomic weights and COSMO-metafiles are given explained insection 5.3 of the COSMO therm Users manual.

USE EXTERNAL QUANTUMCHEMICALENERGIES: The external quantum chemical energies and zero pointenergies from the property files .vap files are not used until this option has been checked.

CHANGE THRESHOLD FOR THE ITERATIVE SELF-CONSISTENCY: Change threshold for the iterative self-consistency cycle for the determination of the chemical potential. A smaller value leads to higher

accuracy of the COSMO therm results but also to a longer computational time due to an increasingnumber of iterations. Default value: 10 -8.

Compound input settings:USE ALL CONFORMER FILES FOUND FOR A COMPOUND: Use all .cosmo , .ccf or .mcos files as conformersthat are found in the database or directory from where the compound is selected. The COSMO filefilenames must follow the name convention of conformer COSMO files in COSMO base (i.e.conformer COSMO files are named by subsequent numbers starting with zero: name0.cosmo,name1.cosmo, , name9.cosmo ). When this option is checked, you will be enabled to make aselection from compounds 0-9.

2.6 Mixture optionsSettings from the M IXTURE OPTIONS panel can be applied to individual temperature / mixture / property lines. The dialog is available as shortcut button Mixture Options. Mixture options willonly be used if the U SE MIXTURE OPTIONS checkbox is activated in the property panel. If severalmixtures or properties are calculated in a single run, the mixture options have to be activated eachtime the property settings are transferred the property selection window, or they will not be usedfor the respective property calculation.

Print options for the COSMO therm output file:SUPPRESS MIXTURE OUTPUT IN.OUT-FILE: Mixture information will not be written to the output file.

7/29/2019 Tutorial-C21-0110.pdf

16/56

16

PRINT DERIVATIVES OF CHEMICAL POTENTIAL: Print the values of the temperature and compositionderivatives of the chemical potentials of all compounds in all mixtures to the output file. SeeCOSMOtherm Users Manual, section 5.6 Chemical Potential Gradients for further information.

Program control settings:

SWITCH OFF TEMP. DEPENDENCY OF HYDROGEN BOND CONTRIB.: Switch off temperature dependency of thehydrogen bond contribution to the total interaction energy of the compound for the completeCOSMOtherm run.

SWITCH OFF TEMP. DEPENDENCY OF VAN DERWAALS CONTRIB.: Switch off temperature dependency of thevan der Waals contribution to the total interaction energy of the compound, active for thecomplete COSMO therm run.

SWITCH OF HYDROGEN BONDING: Switch off hydrogen bonding contribution to the chemical potential.

SWITCH OFF VAN DER WAALS CONTRIBUTIONS: Switch off van der Waals (vdW) interaction energycontribution to the chemical potential.

SWITCH OFF COMBINATORIAL CONTRIB. TO CHEMICAL POTENTIAL: Switch off combinatorial contribution to thechemical potential for the complete COSMO therm run.

DO NOT CHECK FOR CHARGE NEUTRALITY: Overrides the check for charge neutrality of a given mixturecomposition and allows you to compute non-neutral mixtures.

Select compounds printed in .out file: Write to the COSMO therm output file the evaluated information only for the selected compounds.

Helps to shorten the output file if not all evaluated information is required by the user.

Advanced settings: Switch of combinatorial contribution for specific compounds: The combinatorial contribution is switched off for the selected compounds only.

2.7 Output filesFiles produced by COSMO therm and COSMOtherm X are

The regular input file .inp The regular output file with the extension .out

In property calculations the summary table file .tab If the corresponding options are set:

-profiles .prf -potentials .pot -moments .mom -moments .moma

Files and folders forspecial cases such assolvent screening

The summary table file will bedisplayed in a table editor. If theprint options for -profiles or -

7/29/2019 Tutorial-C21-0110.pdf

17/56

17

potentials have been set, the data for the -profiles or -potentials will also be displayed in thetable editor in individual tabs. Moreover, there will be tabs where -profiles or -potentials can beplotted .

Some of the output files can be saved in MS Excel format or (on Windows systems) opened directly

with the standard software connected to .xls files, using the options File Save As orFile Open with MS Excel. These options ar e available for .tab, .prf, .pot, .mom and.moma files.

7/29/2019 Tutorial-C21-0110.pdf

18/56

18

3 Compounds

Apart from the menu and shortcut bars, the COSMO therm X main window has two sections. Thesection on the left may show one of two different tabs. The C OMPOUNDS tab contains a list of

selected compounds. At the bottom of this section, there are buttons to open the F ILE MANAGER,database files or the C OMPOUND WIZARD from which the compounds can be selected. The F ILES tabshows a list of recent calculations.

3.1 Compound selectionThe compound section of the COSMO therm X main window offers various functionalities forcompound selection. There are four DB buttons which open the database index files of thecorresponding level of theory in tabulated form. The locations of the database index files from theCOSMOtherm release are set automatically. Locations for other databases have to be given in theDATABASESpanel of the G ENERALSETTINGSdialog.

Hint: Inside the F ILEMANAGERor the database files, a list of compounds can be highlighted by usingthe Ctrl or Shift keys together with the mouse.

ACTIVATECONFORMERSTREATMENT: If this checkbox is marked and you have selected more thanone conformer for a compound, the conformers will be weighted internally byCOSMOtherm using their COSMO energy and their chemical potential.

SVP DB: COSMO files are calculated on the BP/SVP quantumchemical level, based on AM1 molecular structures.

TZVP DB: Same as SVP-Database, but COSMO files are calculatedon the BP/TZVP quantum chemical level.

ISOCAV DB: COSMO files are calculated using the scaledisodensity (ISOCAV) method, based on optimized molecularstructures on the BP/TZVP quantum chemical level.

DMOL3 DB: COSMO files are calculated on the PBE/DNPquantum chemical level with the DMOL3 program.

FILE MANAGER: Opens the directory tree of your system andenables to choose COSMO files of any quantum chemical leveldirectly from the file system. Make sure that you use anadequate parameterization for the COSMO files. If you do notplan to use any compounds other than those provided withyour COSMO therm installation, it is more convenient and fail-

safe to use the database buttons. OPEN LIST: A list of previously saved compounds can be loaded

with this option. The saved concentrations of the compoundswill also be loaded but not automatically applied. Please selectAPPLY LISTCONCENTRATIONSfrom the extras menu for this feature.

COMPOUND WIZARD: With this tool it is possible to search compounds in all Databases byname, SMILES, CAS-Number, 2D structure and 3D structure. It is also possible to generate a3D structure from smiles and to start COSMO calculations with TURBOMOLE directly fromthe Compound Wizard. See detailed description below.

CLEAR: Clear all compounds from the selection window. Note that individual compounds canbe removed using the Delete key.

7/29/2019 Tutorial-C21-0110.pdf

19/56

19

3.2 The compounds context menuA right mouse button click on one or more compounds inside thecompound list opens a context menu with several options for thehighlighted compound. This option is also available in the databasesearch and the C OMPOUND WIZARDand may vary by applicability.

compound properties conformer properties decompose conformer / combine to conformer open remove from list view gas phase geometry view cosmo geometry view sigma surface view sigma profiles /-potentials convert selection write to list show existing files

COMPOUND PROPERTIES: Pure compound property data canbe edited with this option. Data entries in the dialogcome from the .vap file of the compound. Propertieshighlighted in green indicate that data entries areavailable, while for properties highlighted in blue nodata entries exist so far. Data can be changed or added

and can subsequently be used in the COSMO therm input for the current calculation only or savedpermanently to the .vap file. Note that if applied todatabase comp ounds Save to Vap will change thecorresponding .vap files in the database permanently.The use of the saved pure compound property can beswitched on and off in the G LOBAL OPTIONS dialog. Bydefault the data are used where possible.

CONFORMERPROPERTIES: A conformer weight factor can bespecified. The conformer weight factor is a degeneracy or symmetry factor that has to be used if itis possible to form this conformer in several different ways. Note that this option is only available inthe compound list for compounds with conformers and only if the conformers treatment isactivated.CREATE CONFORMER / DECOMPOSE CONFORMER: If several compounds (not conformers) are highlightedand this option is selected from the context menu, the highlighted compounds will be treated asconformers of a single compound. A name for the compound can be specified.If a single conformer is selected the option will appear as DECOMPOSE CONFORMERand constructindividual compounds of the different conformers of the selected conformer. Note that this optionis only available in the compound list and only if the conformers treatment is activated.OPEN: Opens the .cosmo or .ccf file of the compound in a text editor.

REMOVE FROM LIST: Deletes a compound from the compound list, same as Del key. IEW COSMO GEOMETRY: 3D ball-and-stick model of the molecular geometry from the .cosmo file.VIEW GASPHASE GEOMETRY: 3D ball-and-stick model of the molecular gas phase geometry.

7/29/2019 Tutorial-C21-0110.pdf

20/56

20

VIEW SIGMA-SURFACE: 3D preview of the molecular -surface. This graphic has a lower resolution thanthe graphic you get from a VRML of the -surface in a VRML viewer.VIEW SIGMA-PROFILES /-POTENTIALS: The -profiles and the -potentials of the selected compounds areplotted.CONVERT SELECTION: The selected files can be converted into a variety of other file types like .xyz ,

.pdb or .ml2 .SAVE TO COMPOUND LIST: The selected files can be written to a list which can be used for furtherprocessing. If the complete compound list should be save, the S AVE COMPOUND LIST option from theFILEmenu can be used alternatively.EDIT WEIGHT STRING: Opens the .cosmo or .ccf file in the COSMO weight tool and allows for thesetting of a weight string and correction charges which will be written to the compound list of theinput file. The weight string will not be saved to the .cosmo or .ccf file.EDIT.MCOS-FILE: Opens the .cosmo or .ccf file in the COSMO weight tool and allows for the creationof a .mcos file.

Note that the options EDIT WEIGHTSTRINGand E DIT .MCOS-FILE are available only in the compound listand only if the conformer treatment is deactivated. R efer to the section Atom weighting forinformation on the use of the COSMO weight tool.

The options view cosmo geometry, view gasphase geometry, View Sigma -surface and ViewSigma-profiles /- potentials from the context menu require a COSMO therm run in the background.Output files of the runs are written to temporary files which will be removed when the displaywindows are closed. For the 3D ball-and-stick model of the molecular geometry or the -surface ofthe molecule to be written to permanent files check the corresponding checkboxes in the Extrasmenu. -profiles and -potentials are written to permanent files with the extensions .prf and.pot when the corresponding options in the Options dialog are selected.

3.3 Selecting compounds from databasesAfter opening one of the database parameterizations (e.g. TZVP DB) a window for the compoundsearch and selection appears. Inside the window all implemented databases of the chosenparameterization will show as different tabs. If no additional databases are implemented, only onetab (e.g. Database-TZVP) will be visible. The database tables can be sorted with respect to number,name (which is the name of the .cosmo or .ccf file), CAS-Number, molecular weight (MW),charge and formula. For some compounds, there are several conformers with different -profiles tobe considered. By default, all available conformers are selected. You can uncheck the selection touse only the lowest energy conformer. In case you should need a specific conformer other than thelowest energy conformer, you can us e the Del key to delete the unwanted conformers from theselection or select it from the F ILEMANAGER.

7/29/2019 Tutorial-C21-0110.pdf

21/56

21

The database tables can also be searched for compounds. It is possible to enter a search string

(name, formula, CAS-Number) or open a text file with a list of compound names which will then besearched for in the database. The search can be processed in the current database only or in alldatabases which are opened in the databases dialog, e.g. all databases which are registered in theEXTRAS /GENERALSETTINGS /DATABASESdialog for the corresponding quantum chemical level.

3.4 Compound WizardThe Compound Wizard is a universal tool for adding known or unknown compounds to yourcalculation. It also offers some advanced search options for the database.The wizard makes use of free external tools, which have not been developed by COSMO logic . Wecannot guarantee that all offered functionality will operate smoothly under all possiblecircumstances. The Compound Wizard will be very useful for setting up COSMO therm calculationsin many cases involving compounds that are not readily available from the COSMO databases.The following list gives an overview of the general option:

Search all databases by names, CAS-Number, SMILES, drawn structures or loaded structures Search the free Internet database ChemSpider by compound name Draw two dimensional or three dimensional structures for database searches or to start

quantum mechanical COSMO calculations. Load structures from files Convert SMILES or two dimensional structures to three dimensional structures. This option is

only available in the search results window. Modify an existing molecule to generate a new one.

Start Search:

7/29/2019 Tutorial-C21-0110.pdf

22/56

22

Inside the first window, the name, CAS-Number or SMILES can be given to start the correspondingdatabase search. Alternatively a structure can be drawn or a molecule taken from file. If a quantummechanical COSMO calculation has been started previously, you can also directly go the QM Resultspanel.The search for name, SMILES, CAS-Number or a drawn 2D structure will always lead to the DB

Search Results window. The 2D structure is therefore converted to a SMILES.

The above search for ethanol led to a number of perfect hits (green) and near hits (yellow). Theright column shows in which database the compound was found. After selecting a compound fromthe results list, several options are available:

Use one of the structures for a quantum mechanical COSMO calculation to obtain a .cosmofile for a different parameterization level.

Use structure for 2D or 3D editing if only similar molecules have been found. Add the molecule to the compound list for the COSMO therm calculation.

The Internet database ChemSpider can be used to find a SMILES for a given name. Thisoption is only available if the search was started by compound name.

If the search was started by SMILES or a drawn structure, you can also choose to convert theSMILES to a 3D structure.

In case that a drawn 3D structure or a molecule file should be used for the search, the 3D moleculeeditor will open. Only two options are available after a 3D geometry has been build or openedfrom file. Either use the structure for a quantum mechanical COSMO calculation or restart thesearch with a SMILES generated from the 3D structure. The latter option is useful to search thedatabases for a given 3D Structure.

Start quantum mechanical calculations:If the requested compound could not be found inside the database or not with the needed basis setlevel (e.g. TZVP), a QM calculation is necessary to generate the appropriate .cosmo file. The QMCalculation panel can either be accessed from the DB Search Results or from the 3D editor.

7/29/2019 Tutorial-C21-0110.pdf

23/56

23

Inside the QM Calculation panel you can choose the parameterization level (SVP or TZVP), the typeof calculation (gas phase or COSMO or gas phase and COSMO) and the output file type (.cosmo or.ccf). With S TART CALCULATION(NETWORK) the QM calculation can also be done on a remote machine(Linux only).

After the QM calculation is finished you can transfer the molecules to your compound list to startCOSMOtherm calculations. The QM Results panel can be directly accessed from the Wizard Startingwindow.

Example: GlycofurolDuring a conference you heard that Glycofurol is a nice solvent for special purposes, butunfortunately you dont know anything but its name.

General informations about a remote system are:1. The name or the IP address of a remote machine2. User name on that machine3. Password to log in (will not be saved to disk!)

Those three fields have to be filled in first. To check if the settings are correct, and if a connection can be established,click on check password settings. The Wizard will try to log in and determine the home directory of the user which hasbeen given in the User field.If the connection has been successful, the home directory will be added to the 'Path' field.

4. Path provides the information in which path on the remote machine the job shall run a local fast disk shouldbe chosen here.

5. TURBODIR has to be set to the TURBOMOLE installation directory on the target system.The default behaviourof ssh when starting remote jobs without an explicit shell or terminal is such that not all settings on theremote system are sourced. So it is very likely that your Turbomole settings (like $TURBODIR, $PATH, etc) arenot available in such a case. It is therefore unavoidable to set the PATH to the Turbomole directory on theremote system by hand.

6. The number of CPUs can be left unchanged. Note that this field is not to tell TURBOMOLE how many CPUs orcores are available in general, but how many CPUs shall be used for the calculation of each job!

7. If the background option is activated, the jobs are started with nohup. In this case, TURBOMOLE does not geta notice when the job has finished, so it has to check actively if the job is still running or not. The frequencyfor those checks can be given in minutes.

The queueing system option is described in the next chapter.After settings 1-5 are complete, click on save settings , and the machine with user name and paths will be added to thepull down list of machines for future usage.

7/29/2019 Tutorial-C21-0110.pdf

24/56

24

Open the Compound Wizard and enterglycofurol into the name field, pressenter or the S EARCH BYNAME button tosee if the substance is already insideyour da tabases. Lets assume it is not

there and try the S EARCH THISNAME INCHEMSPIDER button. A tutorial for usingChemSpider is also available directlywithin the Wizard. ChemSpider willfind the SMILES O(CCO)CC1OCCC1 forglycofurol. Enter it into thecorresponding field inside the Wizard and C ONTINUE WITH THISSTRUCTURE /SMILES. Now the wizardperforms a structure search based on the SMILES string. Assuming that the structure can again notbe found in the database the G ENERATE3D STRUCTURE FROMSMILES option is your last resort. The 3DStructure will be generated and a new COSMO calculation can now be conducted by choosing U SEFOR QM CALCULATION.

3.5 Conformers Molecules often can adopt more than one conformation. For COSMO-RS, only conformers withdifferent -profiles are relevant. For each of these conformers, an individual COSMO file is requiredfor the compound input. If compounds are selected from the databases and the checkbox in theuse conf. column is checked, all existing conformer COSMO files will be selected automatically. Ifthe A CTIVATECONFORMER TREATMENTcheckbox is checked, the conformers will be weighted internallyby COSMOtherm using their COSMO energies and their chemical potentials.

If you intend to use your own COSMO files for conformers please be aware that in order to be

identified as conformers by COSMO therm X automatically, the names of the files must follow aconvention. It is also possible to define conformers of a compound manually without following thename convention. Select the corresponding compounds from the databases of the File Manager,highlight them in the compound list using the Control key and the left mouse button, and choosecreate conformer from the right mouse button menu. Note that this option is available only ifthe conformer treatment is activated.

Other useful options for calculations involving conf ormers from the Options global dialog are theprint option Print conformer info (wconf) and the program control option Use all conformerfiles found for a compound (autoc ). For more information on conformer input refer to theCOSMOtherm Users Manual, section 2.2.2 .

3.6 Visualization of -surfaces, -profiles, and -potentialsThe 3D screening charge distribution on the surface of a molecule i can be used to qualitativelydescribe the molecule. Polarity, hydrogen bonding and lipophilicity or hydrophilicity can bevisualized on the molecular surface. The surface screening charges can be converted into adistribution function, the -profile p i ( ), which gives the relative amount of surface with polarity on the surface of the molecule. The -potential, as calculated from eq. 5, can also be visualized.

Example: COSMO charge surface visualization, -profile and -potential.

Select the compounds you would like to visualize. In the Extras menu, check Generate VRML ( -surface) for the COSMO charge surface visualization. Open the G LOBALOPTIONS / ADDITIONAL OUTPUTFILES, check -Profile s (.prf) and -Potential s (.pot) for the generation of the -profile and -

7/29/2019 Tutorial-C21-0110.pdf

25/56

25

potential files. After the calculation has finished, use T OOLS / VMRL VIEWER (COSMOview ) to displaythe -surfaces of the molecules. For more information on COSMO view , please refer to the sectionUsing COSMO view . -Profiles and -potentials can be plotted in a spreadsheet program.The COSMO charge surface, the -profile andthe -potential of a compound can also be

visualized from the File Manager or thedatabases. Highlight a compound with a leftmouse button click. With a right mouse buttonclick you can choose sigma -surface orsigma -profiles / - potentials. A COSMOtherm calculation is run in the background and awindow displaying the chosen property willpop up.

Further information on -profiles and -potentials: COSMO therm Users Manual, chapter 5.

3.7 Using COSMO view COSMOview can be used to display .wrl files generated byCOSMOtherm . COSMOview is included in COSMO therm X andcan be accessed via T OOLS / VRML-VIEWERfrom the main menu.

OPEN : Open a previously generated VRML. Alternatively,open a VRML file by right-clicking a compound and selectingview sigma surface or VIEW MOLECULEfrom the context menu.SAVE GRAPHICS : Graphics can be saved with transparentbackground and/or a small legend optionally. Please note thatsince COSMO view uses an internal color correction, the legendproduced will not be applicable to images obtained by othermeans than COSMO view , e.g. third-party browser plug-ins.HOME : Reset the camera to its initial position.VIEWERSETTINGS : Change color, labels, atom settings, bond settings and so on.

SHOW / HIDE THE SIGMA SURFACE : If a surface is loaded, it can be hidden and shown again.SHOW / HIDE THE MOLECULE ITSELF : The molecule structure can be hidden and shown again.

TOGGLE WIRE FRAME DISPLAY : Instead of closed object surfaces it is possible to show only the wire

frame. Thisoption works for surfaces, atoms and bonds.TOGGLE CHARGE DENSITY PICKER: To get an idea of the quantitative surface charge density at a givenpoint, you can activate the charge picking mode and move the cursor over the -surface. A slider atthe right-hand side will display the charge density at the sport you are pointing on. However thesevalues can only be approximated and are not guaranteed to be entirely precise. This is mainly aneffect of interpolation between the reduced grid size compared to .cosmo files.DISPLAY INFO : Shows a few data on grid size and charge for

Movement: Molecules can be moved using the mouse buttonsRotate the molecule by dragging the mouse with the left button pressed. If you move the mousequickly, you can give the molecule a spin to have it turn by itself.Zoom in and out with the right mouse button pressed or simply by turning the mouse wheel.

Charge picking:

7/29/2019 Tutorial-C21-0110.pdf

26/56

26

To get an idea of the quantitative surface charge density at a given point, you can activate thecharge picking mode with and move the cursor over the -surface. A slider at the right-hand sidewill display the charge density at the sport you are pointing on. However these values can only beapproximated and are not guaranteed to be entirely precise. This is mainly an effect ofinterpolation between the reduced grid size compared to .cosmo files. You may want to check the

file properties .

Please note that like most 3D-viewers, COSMO view requires OpenGL v1.1. If it does not start up atall (especially in X window environments), make sure that both your display and the X client are glxcapable.

7/29/2019 Tutorial-C21-0110.pdf

27/56

27

4 Property input

The larger section of the main window offers a selection of property cards. Inside each card you canadjust parameters like temperature, mole fraction etc. to your issue. Input settings from the

property cards are transferred to the Property Selection panel with the Add button. Changes inthe Mixture Options dialog are taken into account for the property if the Use Mixture Optionscheckbox is activated. The COSMO therm calculation is started with Run Run or from theshortcut bar. In this section, the different options for the calculation of properties are described.There are also examples for some calculations.

By default, COSMO therm produces two sorts of output files for most property calculations: TheCOSMOtherm output file filename.out and a file filename.tab which contains the calculatedproperty information in tabulated form. These files will automatically pop up after the calculationhas finished. Additional output files will be written if the corresponding options in E XTRAS /GLOBAL

OPTIONS

are activated. These output files may contain -moments ( .mom ), atomic -moments(.moma ), -profiles ( .prf ), or -potentials ( .pot ).

4.1 Mixture: Calculation of compound properties in mixtureThis option toggles the COSMO therm calculation of interaction energy terms at the giventemperature and mixture composition. For all compounds i in the compound list, the followingterms will be calculated:

Chemical potential S i of the compound in the mixture from eq (6).Log10(partial pressure [mbar])Free energy of the molecule in the mixture (E_COSMO+dE+Mu)Total mean interaction energy in the mix (H_int): The mean interaction enthalpy of the compoundwith its surrounding, i.e. the interaction enthalpy of the compound which can be used to deriveheats of mixing and heats of vaporization.Contributions to the total mean interaction energy:Misfit interaction energy in the mix (H_MF).H-Bond interaction energy in the mix (H_HB)VdW interaction energy in the mix (H_vdW)Ring correction

For details on the calculation of the energy terms and contributions please refer to theCOSMOtherm Users Manual, section 1.1.

Furthermore, COSMO therm allows for the computation of the contact probability of molecules andmolecule surface segments in arbitrary mixtures. The checkbox Compute Contact Statistics can bechecked to obtain a more detailed contact interaction statistics of all segments of molecules A andB. For more information on the calculation of contact statistics please refer to the COSMO therm Users Manual, section 5.7.

4.2 Vapor pressure

COSMO-RS allows for the estimation of pure compound vapor pressures. The energy of the gasphase E i gas is required for the calculation of the chemical potential in the gas phase, i gas . E i gas can betaken from a gas phase quantum chemical calculation or empirically estimated by COSMO therm . If

7/29/2019 Tutorial-C21-0110.pdf

28/56

28

possible, the quantum chemical calculated value of E i gas should be used: Chec k Energy file inGLOBALOPTIONS(this is the default setting).The vapor pressure option enables the computation of vapor pressures for a given temperature or atemperature range and a fixed mixture concentration. The number of points in a temperaturerange can be up to 100, default value is 10. For each temperature and compound in the mixture the

partial vapor pressures, the chemical potential of the compound in the gas phase and its enthalpyof vaporization are computed and written to the COSMO therm output file. The total vaporpressure of the mixture is written to the COSMO therm table file in tabulated form p VAP vs T . Inaddition the total chemical potentials of the liquid liquid (tot) and of the gas phase gas (tot) , as well asthe heat of vaporization of the mixture Hvap are written to the COSMO therm table file. If three ormore temperature points were calculated in a vapor pressure curve, the total vapor pressure will befitted to Antoine svapor pressure equation ln (p) = A - B / (C + T) , where T is the temperature in [K]and A , B and C are coefficients. The coefficients are written to the COSMO therm output and tablefiles.Note that since the Vapor Pressure option in COSMO therm is intended for the prediction of vaporpressures data from .vap files are not used even if this is indicated in the options. However, ifvapor pressure data are available from a .vap file, they will be printed to the last column of thetable file for comparison.

Example: Calculation of a vapor pressure curve

Select methanol from the TZVP DB.Make sure that Energy file in theGLOBAL OPTIONS is checked. Set thetemperature range from 0C to 70Cthe mole fraction as pure methanol.Pressing A DD transfers the selectedvapor pressure settings to the propertypanel at the bottom. Start thecalculation by pressing R UN.

The total vapor pressures can be readfrom the output file and from thetable file which will open in a separatewindow after the calculation hasfinished.

4.3 Boiling pointThis option enables the iterative optimization of the equilibrium temperature for a given vaporpressure. The temperature of the system is varied and for each temperature the vapor pressure iscalculated. This is repeated until the COSMO therm prediction of the total vapor pressure and thespecified pressure in the input file is below a certain threshold. During the procedure, the partialvapor pressures of the compounds are written to the COSMO therm output file. When the requiredthreshold is met, i.e. convergence is reached, the total vapor pressure of the mixture is written tothe COSMO therm table file.

7/29/2019 Tutorial-C21-0110.pdf

29/56

29

4.4 Activity coefficient calculationThis option computes the activity coefficients of different compounds in the selected solvent orsolvent mixture. For the calculation of the activity coefficient at infinite dilution, the mole or massfraction of the compound of interest has to be set to zero in the composition of the solution. Thechemical potentials j (P) of all pure compounds j and the chemical potentials j (i) in the liquid phase(compound i or compound mixture, respectively) are calculated. The activity coefficients are thencalculated as ln( j ) = ( j (i) j (P)) / RT .

It is also possible to calculate the activity coefficients at a given finite concentration. This is achievedby setting the mole or mass fraction of the compound of interest to the required value in thecomposition of the solvent. The compound in question is thus treated as part of the solvent.By checking the A DVANCED SETTINGSa reference state for the activity coefficient can be chosen.

Example: Calculate the activity coefficient of aspirin in water

Choose the compounds, aspirin andwater, from the TZVP database. Bydefault, both aspirin conformers areselected from the database and theconformer treatment is activated toaccount for a conformer mixture.Then, set the temperature to thedesired value, 25 C, set the watermole fraction to 1.0 (check P URE), andtransfer the selection to the propertypanel with the A DD button.

Windows displaying the output and table files will open after the calculation has finished.By checking the A DVANCED SETTINGSa reference state for the activity coefficient can be chosen.

4.5 Henry law coefficient calculationThis option allows for the computation of Henry law coefficients H(i) in compound i. The chemicalpotentials j (P) of all pure compounds j and the chemical potentials j (i) at infinite dilution incompound i are calculated. Then the Henry law coefficients H j (i) for all compounds j are calculatedfrom the activity coefficients and the vapor pressures of the compounds are written to theCOSMOtherm output and table files. It is also possible to calculate the Henry law coefficients at agiven finite concentration, i.e. in a mixture of solvents.The Henry law coefficient depends on the pure compound vapor pressure. For each compound,there are several possibilities to calculate or approximate this property. In order of increasingaccuracy you might:

Use the COSMO therm approximation of the vapor pressure using the approximated gasphase energy of the compound. This is the default if no .energy file is present and requiresno additional input.

Use the COSMO therm approximation of the vapor pressure using the exact gas phaseenergy of the compound from the .energy file. This option is set by default. (G LOBALOPTIONS: check E NERGY FILE)

Use the Wagner, DIPPR, or Antoine equation ln( p j 0) = A B / (T + C) to compute the vaporpressure at the given temperature. If available, data for these equations will be read fromthe .vap file if the V APOR PRESSURE / PROPERTY FILEoption is checked in the G LOBALOPTIONS.Data can also be entered in the COMPOUND PROPERTIESdialog from the context menu of thecompound list.

7/29/2019 Tutorial-C21-0110.pdf

30/56

30

Enter the exact value of the vapor pressure for this temperature via the COMPOUND PROPERTIES dialog from the context menu of the compound list

The Henry Law Coefficient option also allows for the calculation of the Gibbs free energy ofsolvation in different reference frameworks.

4.6 Gas solubilityWith this option the solubility of a gas in a solvent or solvent mixture can be calculated in aniterative procedure. For each compound j the mole fraction x j is varied until the partial pressure ofthe compound p j = p j 0 x j j (with the activity coefficient j and the pure compound vapor pressure p j 0)is equal to the given reference pressure p .Like the calculation of the Henry Law Coefficient, the calculation of a gas solubility requires theknowledge of the pure compound vapor pressure. For options to give the pure compound vaporpressure please refer to the Henry law coefficient calculation section.

Example: Gas solubility of methane in waterSelect the compounds, water and methane, from the TZVP database. Set the temperature, 25 C,and the pressure, 1013.25 mbar, in the Gas-Solubility card. Set the solvent composition to purewater . Transfer the settings to the Property Selection by pressing ADD and run the program.

Windows displaying the output and table files will open after the calculation has finished.

4.7 SolubilityThe SOLUBILITYoption allows for the automatic computation of the solubility of a liquid or solidcompound j in a solvent i. Within the calculation all compounds are also considered solutes, eventhe solvents themselves. This approach is optimized for the calculation of many solutes in a limitednumber of solvents. If the solubility of a single solute should be calculated in a large number ofsolvents the S OLVENTSCREENINGpanel offers an appropriate solution.The solubility is defined as:

)] / )[exp((log)(log ,1010 RT G x fusio n jsolvent j

pur e j j

7/29/2019 Tutorial-C21-0110.pdf

31/56

31

COSMOtherm can directly calculate the chemical potentials j pure of all pure compounds j and thechemical potentials j solvent at infinite dilution. The free energy of fusion Gfus is zero for liquidcompounds and has to be given or estimated for solid compounds. The computed solubility x (0) j is azeroth order approximation, which is valid only for small concentrations of the solute. If thesolubility is large ( x j > 0.1), x (0) j is a poor approximation, but x j can be refined iteratively by

resubstitution of x (0) j into the solubility calculation. This procedure can be repeated until thedifferences in the computed value of x j are below a certain threshold. In COSMO therm X, thisprocedure is turned on by checking the I TERATIVEcalculation type in the solubility panel.

As mentioned above the Gibbs free energy of fusion Gfus has to be taken into account for solidsolutes. Gfus can be read from the vapor pressure / property file or from the compound line in thecompound input section of the COSMO therm input file. A temperature dependent heat of fusioncan also be calculated if the compounds enthalpy or entropy of fusion ( Hfus or S fus ) and meltingtemperature are known. To add Gfus (or Hfus or S fus and T melt ) to the compound input lines openthe COMPOUND PROPERTIES dialog for the compound. Alternatively, Gfus can be estimated by

COSMOtherm using a QSPR approach. QSPR parameters are read from the parameter file, ifpossible, but can also be given explicitly when the A DVANCED SETTINGScheckbox is checked. Since oneof the QSPR parameters is the chemical potential of the compound in water, water has to beincluded in the compound list even if it is not present in the system. For further information referto the COSMO therm Users Manual, section 2.3.4.

By default, the output of the solubility option is in logarithmic mole fractions, log 10(x). Additionally,the mass based solubility is written to the table file. The definition applied for the mass basedsolubility can be changed in the A DVANCED SETTINGS:

Default:solvent

j

MW MW

j j xw (popular in drug solubility screening)

Definition 2:solvent j

j

MW x MW

j j xw )1( (popular in engineering

Mass fraction:solvent j j j

j

MW x MW x MW

j j xw )1( (popular in chemistry)

The default definition is in principle an approximation to definition 2 for low solubilities.For further information about the definition of the mass based solubility, refer to the COSMO therm Users Manual, section 2.3. The decadic logarithm of the molar solubility (log 10(S [mol/l])) will be written to an additionalcolumn in the table file. To calculate the solubility in the more commonly used g/L units thedensities have to be know and will therefore be estimated by COSMO therm . Please note, that thisestimation introduces an additional error to the results.

Example: Solubility of glycol in hexane

In principle, there are two ways to do this. If the liquid solubility of the compound in question isexpected to be low, you can use the S OLUBILITYoption. Alternatively, you can calculate the Liquid-Liquid Equilibrium (LLE) and search the phase diagram for the LLE point. The LLE point can also beprinted to the end of the table fileFirst, select the compounds, glycol ( glycol0.cosmo , glycol1.cosmo ) and hexane(hexane.cosmo ) from the TZVP database. Check t he Activate conformer treatment option . In theSolubility card, set the temperature, 25 C, the state of the solute to L IQUID and the calculation type,ITERATIVE. Then, check P URE in the Solvent paragraph for hexane. Add the settings to the property

7/29/2019 Tutorial-C21-0110.pdf

32/56

32

panel and run the calculation. The COSMO therm output and table files will pop up after thecalculation has finished.

4.8 Solvent screeningThe solvent screening option does work similar to the solubility option and is of course based onthe same thermodynamics (Please note, that the definition for the mass based solubility output isfixed to the default, see solubility). It is especially adjusted to fit solvent screening purposes, i.e. to

predict the solubility of one solute in a list of solvents.In addition to the absolute solubility, a relative screening option is available for solid compounds.As in general the Gibbs free energy of fusion Gfus is one of the largest error sources for thesolubility of solids, the relative screening options avoids this error by neglecting Gfus . The result is arelative solubility ranking. The numbers thus given contain all relevant information about solute-solvent interactions, which means that they represent trends of the solubility in different solvents,but they are no absolute solubility values.In contrast to most other options the screening cannot be done in a single COSMO therm run. Theresult is that many input files have to be generated and stored. A solvent screening run can thusnot be loaded by the O PEN option from the F ILE menu and a special O PEN SCREENINGFILE option hasbeen implemented, which opens an .xml file with all necessary information stored. When startinga solvent screening run the individual input, output and tab files are stored inside a new directorynext to you job file.

Liquid solutes and relative solubility:The use of the solvent screening option is straightforward in these cases. Select the solute, choose anon iterative (infinite dilution) or iterative (finite concentration) type of calculation and add allsolvents or solvent mixtures to the Property Section. Please note, that the R ELATIVE SCREENINGisalways calculated in infinite dilution (non iterative).The result may look like below:

7/29/2019 Tutorial-C21-0110.pdf

33/56

33

In addition to the logarithm of the solubility in mole fractions, the chemical potential of the puresolute j pure , the chemical potential in the solvent j solvent and the solubility in gram per gram solventare given (default definition, see also Solubility). The other values are included for generalinformation purposes.

To illustrate the meaning of relative solubility (definition 2 has been used) the following figureshows octanoic acid in different solvents at 25C. The graph is not automatically generated.

h 2 o

1 - o c t a n

o l

n - b u t y l a c e t a t e

1 - p e n t a n

o l

1 - b u t a n

o l

e t h y

l a c e t a t e

2 - b u t a n

o l

p r o p a n

o l

2 - p r o p a n

o l

d i o x a n e

t h f

-3.50

-3.00

-2.50

-2.00

-1.50

-1.00

-0.50

0.00

Relative Solubility of Octanoic Acid

l o g 1 0 ( w

_ R S ) [ g

/ g_

s o

l v e n t ]

The logarithm of the best solubility in gram/gram solvent is set to 0 and all other solvents are givenrelative to the best solvent. In the above example tetrahydrofuran (thf) is clearly the best solvent. Asolvent with a log10(w_RS) value of -1.00 yields a solubility, which is decreased by a factor of 10compared to thf, e. g. the solubility in water is about 2000 times worse.

Absolute solubilities for solid compounds:When the absolute solubility of solid soluteshould be computed, the free energy offusion cannot be neglected. As the absolutesolubility depends on the concentration ofthe solute itself, the iterative procedure(fibite concentration) is always used.After selecting the corresponding options(State of solute = solid, and Absolute values is checked) three different options for the estimationof Gfus appear:

An experimental solubility in one of the solvents or solvent mixtures can be used to

determine Gfus of the solute. If the reference solvent is chosen carefully, i.e. it is known,that COSMO therm results are usually in good agreement with experimental data for thissolvent, this option might give results closest to measurements due to error cancellation. If,

7/29/2019 Tutorial-C21-0110.pdf

34/56

34

however, COSMO therm fails to make good predictions for the reference solvent, the errorsmight add up instead of canceling.The experimental solubility can be given in mass fraction, mole fraction or mg/g solvent

according to definition 2 (solvent j

j

MW x MW

j j xw )1( ).

In rare cases it might happen, that the reference solvent leads to a negative Gfus. As thisunphysical value cannot be used by COSMO therm Gfus = 0.0 is used instead. The originalvalue of the reference solvent cannot be reproduced in this case and all resulting solubilitieswill have a shift!

An experimentally measured value for Gfus or (or Hfus or S fus and T melt ) can be taken fromthe property ( .vap ) file of the solute. The accuracy of this method depends onextrapolation of Gfus at the melting point to the temperature where the solution iscalculated.

A quantitative structure property relationship (QSPR) can be used. The predictive accuracyof this option is on average the worst of the three choices.

4.9 Salt solubilityIn COSMOtherm a salt A -C+ always is treated by means of its anion A - and cation C +. To obtain thesolubility of a salt, the chemical potentials of the individual ions A - and C + and the free energy offusion Gfus of the salt A -C+ have to be determined. The salt solubility is then computed from themean chemical potentials of the ions and the free energy of fusion. COSMO therm will calculate atemperature dependent free energy of fusion if the enthalpy or entropy of fusion of the salt ( Hfus or S fus , respectively) and the melting temperature ( T melt ) are known. In the Salt Solubility card, thefree energy of fusion can be entered directly or, alternatively, the enthalpy or entropy of fusionand the melting temperature can be entered. If the heat capacity of fusion Cp fus is entered, it willbe used to describe the temperature dependency of the Gibbs free energy of fusion.The computed mass fraction salt solubility in [g Salt /g Solvent ] can be compared directly to experimentaldata. For comparison of the computed salt mole fraction with experimental data, depending on thereference state of the salt solubility measurement, it may be necessary to convert the computed saltmole fracti on value along the guidelines given in section 5.9 Ionic Liquids of the COSMO therm Users manual.

The default output of the salt solubility option is the mass based solubility. The definition appliedfor the mass based solubility can be changed in the A DVANCED SETTINGS:

Default:solvent

j

MW MW

j j xw (popular in drug solubility screening)

Definition 2:solvent j

j

MW x MW

j j xw )1( (popular in engineering

Mass fraction:solvent j j j

j

MW x MW x MW

j j xw )1( (popular in chemistry)

The default definition is an approximation to definition 2 for low solubilities.For further information about the definition of the mass based solubility, refer to the COSMO thermManual .

7/29/2019 Tutorial-C21-0110.pdf

35/56

35

Example: Prediction of the solubility of NH 4Cl in several solvents

Select the compounds, water ( h2o.cosmo ),ethanol (2 conformers), 1-octanol, NH 4+ (nh4.cosmo ), and Cl - (cl.cosmo ), from the TZVP

database. In the Solvent definition box, set thesolvent composition to pure water. Then definethe salt composition in the Salt definition box:Check the checkboxes in the cl and nh4compound lines. The stoichiometric coefficientsare set to 1 automatically, which is correct forNH4Cl. Enter the value for the enthalpy of fusion(-314.55 kJ/mol) and the melting pointtemperature (340 C) . Transfer the settings to the Property S ection by pressing ADD. Then, changethe solvent composition to pure ethanol (check P URE in the compound line for ethanol) and transferthe settings to the Property Section by pressing A DD. Change the solvent composition to pure 1-

octanol and transfer the settings again to the Property Selection by pressing ADD and run theprogram.

4.10 Partition coefficient calculation (log P)Partition coefficients of solute j between solvents i 1 und i 2 are defined as P 1,2 = c j 1 / c j 2, with c j 1 and c j 2 being the concentrations of solute j in i 1 and i 2, respectively. The calculation of the partitioncoefficient logP is accomplished via computation of the chemical potentials j (1) and j (2) of allcompounds j in infinite dilution in pure compounds i 1 and i 2, respectively:

] / ) / )[exp((log)(log 12)2()1(1010 totaltotal j j C C RT P (8)

The ratio of total molar concentrations C 2 total / C 1total will be estimated from the COSMO volumes bydefault, unless a value is entered in the Log P card. With the T HERMODYNAMIC PARTITIONoption, theratio will be set to 1, which corresponds to a logP definition by mole fractions. The input of a ratioof total molar concentrations will be necessary if the experimental density of at least one of thetwo solvent phases differs substantially from a linear interpolation form the individual phasecompounds. In this case the estimate from the COSMO volumes, based on the assumption of anincompressible liquid, will be poor. Furthermore, the mutual solubility of the solvents in each otherhas to be taken into account when computing j ( 1) and j ( 2). It is possible to give finiteconcentrations in the solvent mixture section.

Example: Prediction of octanol / water partition coefficients

Select your compounds, water, 1-octanol and aspirin from the F ILEMANAGER. Select the computeoctanol-water partition option:

COSMOtherm automaticallychooses the correct phasecompositions . As you can see the

wet octanol phase contains0.24 mole fractions of water.Finally, add your settings to the

7/29/2019 Tutorial-C21-0110.pdf

36/56

36

property panel and run the program. The partition coefficients can be read from the output andtable files. In the table file, the results are listed (Please note, that the exact numerical values mayvary due to changes in the parameterization.

4.11 Calculation of pK A

The pK A of a solute j can be estimated from the linear free energy relationship: (LFER),

)(pK 10A jion

jneutral GGcc (9)

where G j are the free energies of the neutral and the ionic compounds.The pK A option allows for the computation of the pK A value of a compound in a solvent i (usuallywater). The free energies G j in the solvent at infinite dilution are computed and the pK A isestimated from the above LFER. Thus, to obtain a pK A value it is necessary to do quantum chemicalCOSMO calculations of a molecule in its neutral and in its ionic state. Since the LFER is valid for bothanions and cations it is possible to estimate acidity as well as basicity. The LFER parameters c 0 and c 1 are read from the COSMO therm parameter file by default.pKA prediction by COSMO therm is not restricted to aqueous acid pK A. However, both aqueous basepKA prediction and pK A in solvents other than water require reparameterization of the pK A LFERparameters. LFER parameters for aqueous base pK A, pK A in solvents dimethylsulfoxide (DMSO) andacetonitrile at room temperature are shipped within the COSMO therm parameter filesBP_TZVP_C21_0110.ctd and BP_SVP_AM1_C21_0110.ctd . The parameterizations will be used byCOSMOtherm if the corresponding options are selected from the pK A card. Please note, that thesolvent has to be set corresponding to the selected option for the LFER parameters. LFERparameters for solvent-solute systems other than those provided by COSMO therm or fortemperatures other than room temperature can be set by selecting the A DVANCED SETTINGScheckbox

to enter the LFER parameters.

Note that for secondary and tertiary aliphatic amines COSMO therm systematically underestimatesthe base pK A. This underestimation is the result of a well known problem of continuum solvationmodels like COSMO with aliphatic amines and amino-cations in polar solvents. The error issystematic and can be accounted for by a simple correction term. Refer to the COSMO therm UsersManual, section 2.3.6 for directions.

For the computation of higher states of ionization, the neutral and singly charged ionic specieshave to be replaced by higher ionized species.

Example: Calculation of the aqueous pK A of ammoniakSelect the solvent (water), and the neutral and ionic compounds (NH 3, NH4+), from the TZVP DB. Setthe temperature, 25 C, and set water as the solvent. Set the neutral and ionic compounds from themenus. Use the pK a parameters for bases in water. Note that it is possible to reset the compoundsand also add them to the input. In that case, COSMO therm will do more than one propertycalculation and write the results to the output and table files. Since we have chosen roomtemperature and water as solvent for the calculation, no further settings are necessary. If you wantto use your own LFER parameters, input is possible via the A DVANCED SETTINGSoption. Save the inputfile and run the calculation. The COSMO therm output and table files will open after the calculationhas finished.

7/29/2019 Tutorial-C21-0110.pdf

37/56

37

The table file lists the computed pK A(experimental pk a for NH 3 /NH4+ = 9.24)

4.12 Vapor liquid-equilibria (VLE) and liquid-liquid equilibria (LLE)COSMOtherm allows for the computation of phase diagrams (VLE and LLE) of binary, ternary orhigher dimensional ( multinary ) mixtures. It is possible to calculate phase diagrams at fixedpressure (isobaric) or at fixed temperature (isothermal). The pressure or temperature has to begiven in the input. The program automatically computes a list of concentrations covering the wholerange of mole fractions of the binary, ternary or multinary mixture. At each point the followingproperties are calculated:

the excess properties HE and GE , the activity coefficient i , the partial vapor pressures p i = p i 0 x i i , the total vapor pressure of the system p (tot) , and the concentrations of the compounds in the gas phase y i

The total pressures used in the computation of a phase diagram are obtained from

iiiitot x p p 0)( (10)

The p i 0 are the pure compound vapor pressures for compounds i . x i are the mole fractions of thecompounds in the liquid phase and i are the activity coefficients of the compounds as predicted byCOSMOtherm . Ideal behavior in the gas phase is assumed. Vapor mole fractions y i are obtainedfrom the ratio of partial and total vapor pressures:

)(0 / tot iiii p x p y (11)

Thus, th e computation of phase diagrams requires the knowledge of the pure compounds vaporpressure p i 0 at a given temperature. There are several possibilities to calculate or approximate thisproperty, as described in the Henry Law Coefficient section. By default, the COSMO therm approximation of the vapor pressure, using the approximated gas phase energy of the compound,is employed, unless the use of energy files or vapor pressure / property files is specified in theGLOBALOPTIONS. For other options, experimental data can be entered in the COMPOUND PROPERTIES dialog from the compound list context menu.

Phase diagrams can be calculated either at a fixed given temperature or at a fixed given pressurewith variable temperatures. In an isobaric calculation, COSMO therm will compute the mixtureproperties and vapor pressure for each concentration at different starting temperatures anditeratively converge to the temperature corresponding to the given pressure.

7/29/2019 Tutorial-C21-0110.pdf

38/56

38

COSMOtherm also offers the possibility to compute phase diagrams of a binary mixtures of an IonicLiquid (IL) phase with an additional solvent phase. Because in COSMO-RS theory any Ionic Liquid ordissoluted salt phase has to be treated by means of the individual ions forming the IL or salt, abinary phase diagram comp utation has to be conducted in the form of a pseudo -binarymulticomponent phase diagram with the boundary condition of the anion and cation

concentrations forming the IL or salt having a fixed ratio according to the IL / salt stochiometry. Thismeans that within COSMO therm , the IL / salt is treated by means of the individual ions, but onoutput, the results of the individual ions properties are combined to form a single IL or salt phase,i.e. in the output of COSMO therm the laboratory binary definition is used for binary calculationsinvolving Ionic Liquids. For information about the conversion from the pseudo -binary frameworkto the laboratory -binary framework refer to sections 2.3.7.3 and 5.9 of the COSMO therm UsersManual.

For binary mixtures, COSMO therm also offers the possibility to automatically search for miscibilitygaps. The liquid-liquid equilibrium properties are calculated from

II i

II i

I i

I i x x (12)

where superscripts I and II denote the two liquid phases. If the Calculate LLE point option is used,the COSMO therm table file will be modified according to any miscibility gap that has beendetected. At all points within the miscibility gap the vapor pressures (or for isobaric calculations thetemperatures) and the mole fractions in the gas phase y i will be replaced by the values of the LLEpoints. From the table file any miscibilit