Antioxidant effects of C60 derivatives

A DFT study of the reaction mechanism

M. Swart, S. Osuna and M. Solàmarcel.swart@icrea.es

Objective:systems in

biomedicine

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Reactivity and chemical bonding in biomedicine

• Reactivity and regioselectivity endohedral fullerenes

• Chemical bonding in DNA triplexes

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Reactivity and chemical bonding in biomedicine

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• Nanocages: reactivity and chemical bonding– 662 atoms

background:parallellization on

MareNostrum

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Parallellization on MareNostrum

• Programs used:– ADF version 2007– Open-MPI

• ADF example:– Ptcomp_METECC

• DFT functional: BP86

• Basis set: DZP orTZP

• Pt(PPh3)3CO (105 atoms)

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Parallellization on MareNostrum

cpus

sec. DZP

red. sec. TZP

red.

4 3165

8 1717 0.54

8681

16 932 0.54

4395 0.51

32 580 0.62

2515 0.57

64 372 0.74

1512 0.60

128 300 0.86

998 0.66

• Good performance of up to at least 64-128 cpus

• Annual report BSC 2007• p. 224-225

7

background:fullerenes

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Structure and discovery of fullerenes

• Kroto, Smalley and Curl tried to simulate the conditions of the giant red stars in the laboratorium, and noted in the mass spectra the appearance of peaks corresponding to 60 and 70 atoms.– Nature 1985, 318, 162

C60: buckminsterfullerene

Buckminster Fuller’s geodesic dome (Expo ’67 Montreal)

C60

C70

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Metallofullerenes

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Heterohedralmetallofullerene

Exohedralmetallofullerene

Endohedralmetallofullerene

The so-called TNT (trimetallic nitride template) endohedral fullerenes are most studied, because they are obtained in macroscopic quantities.

Sc3N@C80, Sc3N@C68, Sc3N@C78

computationaldetails

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Computational details

• Programs used: ADF version 2007QUILD (model Hessian TS !)

• DFT functional used:BP86• Basis set: DZP for optimizations, frozen-core• Relativistic corrections: ZORA• Single-points: BP86/TZP//BP86/DZP

• Additional software: program POAV3

• All TSs have been characterized through the calculation of theanalytical frequencies, to have one (and only one) imaginary frequency – MareNostrum, Barcelona (32-64 processors, 96 hours)

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At this level of theory the barrier is underestimated by ca. 6 kcal·mol-1

Barrier parent Diels-Alder reaction: 18.6 kcal·mol-1

J. Comput. Chem. 2008, 29, 724-734

results:previous reactivity

studies (BSC)

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Reaction studied

• Study of the Diels-Alder reaction

• Study of:– thermodynamics– kinetics

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C78 butadiene

M3N@C78 butadiene

M=Sc,Y

J. Am. Chem. Soc. 2009, 131, 129-139J. Am. Chem. Soc. 2008, 130, 6206-6214

Reactivity of non-equivalent bonds of free C78 and Sc3N@C78

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We have studied the Diels-Alder reaction over the 7 non-equivalent [6,6] bonds, and over the the 6 non-equivalent [5,6] bonds.

J. Am. Chem. Soc. 2008, 130, 6206-6214

Bonding model: Ionic (Sc3N)6+@C786-

Reaction barriers (kcal/mol)

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[6,6] Pyracilenic

[6,6] Pyracilenic [5,6]

Corannulenic

[6,6]Type B

[6,6]Type B

[5,6]Corannulenic

Barrier parent Diels-Alder reaction: 18.6 kcal·mol-1

J. Am. Chem. Soc. 2008, 130, 6206-6214

Comparison of Y3N@C78 and Sc3N@C78

• We have studied the DA reaction over all non-equivalent bonds:

– 13 in D3h-C78, 13 in D3h-Sc3N@C78

– 24 in Y3N@D3h-C78

17J. Am. Chem. Soc. 2009, 131, 129-139

Regioselectivity of the reaction is clearly determined by the encapsulated cluster inside the cage:

free: b, 1, 7

Sc3N: 6, 4, c

Y3N:d, 6, 4

Short [6,6] bonds Situated far away from the Sc3N influence

Large [5,6] bonds + close to Y3NShort [6,6] bonds + far away from Y3N

Short bonds, preference for [5,6]

Preferences Sc/Y D3h-C78

18J. Am. Chem. Soc. 2009, 131, 129-139

Sc

ScSc

Y

Y Y

D3h-C78

YY Yh

h= 0.69 Å

d

h= 0.60 Å [0.55,0.73]

hY

Y Y

Edef(diene)= 12.9 [12.9,27.1]

distdist= 1.69 Å

YY Y

dist= 2.20 Å

+ :CH2

Why is large bond d so reactive in Y3N@D3h-C78 ?

19J. Am. Chem. Soc. 2009, 131, 129-139

Reactivity of Ng@C60 and Ng2@C60

• Encapsulation of noble gas dimers may lead to Ng2 chemical bond

• Krapp, Frenking, Chem. Eur. J. 2007, 13, 8256-8270

• Effect on reactivity unknown– difficult to predict because of opposing effects

• reduction of electron affinity• increase of pyramidalization

20Chem. Eur. J. 2009, in press

Reaction barriers (kcal/mol) for Ng2@C60

21Chem. Eur. J. 2009, in press

results:antioxidant effects

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Fullerene derivatives for superoxide dismutation

• Antioxidant activity of C60 derivatives– carboxyfullerene

tris-malonyl C60 (C3)

– degradation of damaging superoxide O2

– • radical

• Possible future application in (bio)medicine– mechanism of action is

currently unknown

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• C3 compound

submitted

Proposed reaction mechanism carboxyfullerene C3

24submitted

Energy profile (kcal/mol)

25submitted

Low barriers

Deactivation of superoxide radical

• TS1 • TS2

26submitted

concludingremarks

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conclusions

• ADF well parallellized– suitable for use on MareNostrum (RES)

• Exohedral fullerene reactivity depends very much on encapsulation (M3N, Ng, Ng2)

• Mechanism of action of superoxide dismutation by carboxyfullerene shown

• Computing time on RES-resources vital for these studies

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acknowledgments

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Collaboration metallofullerenes:Josep Maria CampaneraJosep Maria Poblet

Girona Seminar 2010

• IX Girona seminaron Electron Density, Density Matrices, and Density Functional Theory

– July 5-8, 2010

– dedicated to 70th birthday of Prof. Ramon Carbó-Dorca

– more info: http://iqc.udg.edu/gs2010

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