Polyhedron 52 (2013) 128–138

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Polyhedron

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Synthesis, characterization and coordination chemistry ofaminophenylbenzothiazole substituted 1,4,7-triazacyclononane macrocycles

José Barreto a, Taracad K. Venkatachalam a,b, Tanmaya Joshi a, Ute Kreher a, Craig M. Forsyth a,David Reutens b, Leone Spiccia a,⇑a School of Chemistry, Monash University, Clayton, Victoria 3800, Australiab Centre for Advanced Imaging, The University of Queensland, St. Lucia QLD 4072, Australia

a r t i c l e i n f o

Article history:Available online 2 November 2012

Dedicated to Alfred Werner on the 100thanniversary of his Nobel Prize in chemistryin 1913.

Keywords:Macrocycles1,4,7-TriazacyclononaneCoordination chemistryCopper(II) complexesBenzothiazolesX-ray structures

0277-5387/$ - see front matter � 2012 Elsevier Ltd. Ahttp://dx.doi.org/10.1016/j.poly.2012.10.029

⇑ Corresponding author. Tel.: +61 3 9905 4526; faxE-mail address: leone.spiccia@monash.edu (L. Spic

a b s t r a c t

The synthesis and spectroscopic characterization of four new 2-(4-aminophenyl)benzothiazole substituted1,4,7-triazacyclononane derivatives with and without appended pyridyl groups on the macrocycle isreported: 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-1,4,7-triazacyclononane (L1), 1-(2-(4-amino-phenyl)benzothiazolyl)-2-oxoethyl)-4-(2-pyridylmethyl)-1,4,7-triazacyclononane (L2), 1-(2-(4-N-meth-ylaminophenyl)benzothiazolyl)-2-oxoethyl)-4-(2-pyridylmethyl)-1,4,7-triazacyclononane (L3), 1,4-bis(2-pyridylmethyl)-7-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-1,4,7-triazacyclononane (L4). Theligands have been applied in the synthesis of a series of copper (II) complexes, [Cu(L1)(OH2)](ClO4)2�0.5ACN(C1), [Cu(L3)](ClO4)2�ACN (C2) and [Cu(L4)(OH2)](ClO4)2�0.5THF (C4) whose structures have been deter-mined by X-ray crystallography. As commonly observed for Cu(II) complexes of 1,4,7-triazacyclononanederivatives, the geometry of the metal centre ranges from distorted square pyramidal to pseudo-octahedral.Notably, the amide carbonyl coordinates to the copper(II) centre in C1 and C2 but not in C4 where the pres-ence of an additional pyridyl group results in an N5 coordination sphere.

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1. Introduction

The coordination chemistry of macrocycle-based ligands con-tinues to be an exciting field of chemistry a century after the NobelPrize was awarded to Alfred Werner, due to the plethora of poten-tial applications that can be envisaged. One particular area of focushas been concerned with the development of these types of ligandsfor application as ion selective chemosensors. In this regard, 1,4,7-triazacyclonane, tacn, derivatives have been found to be particu-larly useful principally due their extraordinary ability to bindstrongly to various metal ions. Incorporation of 2-pyridylmethylpendants has been shown to increase the stability of tacn metalcomplexes due to coordination of the pendant arm [1–3]. A fluores-cent molecule can be incorporated to the tacn ring, acting as fluo-rophore for the detection of the compound and allowing the studyof the interaction between the ligand and different metal ions insolution by fluorescence spectroscopy as complexation can giverise to changes in the excitation state of the ligand [4–6].

The benzothiazole derivative, 2-(4-aminophenyl)benzothiazoleand its analogs constitute a class of agents with potent antitumoractivity. For example, they act as aryl hydrocarbon receptor(AhR) agonists translocating into the sensitive tumor cell nucleus

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: +61 3 9905 4597.cia).

where they induce the production of cytochrome P-450 isoform(CYP1A1). Conversion of these drugs into electrophilic species re-sults in the formation of benzothiazole–DNA complexes whichcauses DNA damage and activates the apoptotic machinery leadingto cell death [7–9].

The benzothiazolyl unit is an excellent acceptor which can par-ticipate in the formation of donor–p–acceptor (D–p–A) type com-pounds [10,11]. As a consequence, benzothiazole compounds haveamyloid binding capacity and can be applied in the diagnosis ofAlzheimers related diseases. Towards this end, potential amyloidbinding agents have been labeled with radioactive isotopes andexamined as imaging agents. These were found to be stablein vivo and to possess acceptable pharmacological properties[12]. For example, the utility of 11C-labeled (N-methyl-[11C]2-(40-methylaminophenyl)-6-hydroxybenzothiazole [13] as anamyloid imaging agent have been demonstrated through in vivohumans trials.

A few studies have explored the optical properties of 2-phen-ylbenzothiazoles attached to a macrocycle unit. The influence ofdifferent alkali and earth alkali metals on the absorption andfluorescence spectra of an aza-15-crown-5 macrocyclic compoundcontaining a phenylbenzothiazole unit was studied by Mateevaet al. [14,15]. They found that at high concentration, Ba2+ and Ca2+

affect both the absorption and emission spectra of the compound,whereas other smaller alkali and alkaline earth metal ions showed

J. Barreto et al. / Polyhedron 52 (2013) 128–138 129

no effect. In this case, the selective decrease of the fluorescence onaddition Ca2+ and Ba2+ is due to the ability of the metal to fit insidethe macrocycle cavity and also because of their higher charge[14,15].

Encouraged by their remarkable biological profile shown in var-ious fields including cancer and neurology, we chose to attach ben-zothiazole pendants to various tacn compounds and to investigatethe coordination chemistry of these tacn-benzothiazole deriva-tives. Herein, we report the synthesis of a series of 1-(2-(4-amino-phenyl)benzothiazolyl)-1,4,7-triazacyclononane derivatives, whichhave up to two pyridyl groups attached to the macrocycle, andtheir utilization in the synthesis of the corresponding copper(II)complexes. X-ray crystallography has been used to explore theinfluence of the number of pyridyl donors on the metal coordina-tion environment.

2. Experimental

2.1. Materials and methods

All chemicals were purchased from Sigma–Aldrich and wereused without further purification. Unless otherwise noted eachreaction was conducted under a nitrogen atmosphere. The synthe-ses of 1,4,7-triazacyclononane (tacn), 1,4,7-triazacyclo[5.2.1.04,10]-decane, 6, and 1,4-bis(2-pyridylmethyl)-1,4,7-triazacyclononane(dmptacn), 16, were carried out following literature procedures[1,16,17].

NMR spectra were obtained either on a 200, 300 or 400 MHz(Bruker or Varian) instrument with an auto probe assembly usingeither CDCl3 or d6-DMSO as solvent. Chemical shifts are reportedas d values in parts per million. In the case of CDCl3, the TMS signalwas used as a reference at 0 ppm and for the d6-DMSO solvent, thesignal at 2.49 ppm was used as a reference. Splitting patterns weredesignated as follows: s, singlet, d, doublets, t, triplets, m, multipletand br broad peak. Fourier transform infrared (FT-IR) spectra wererecorded on a on a Perkin Elmer 1600 Series FTIR Spectrometer inthe range 4000–400 cm�1, with a resolution of 4.0 cm�1. Sampleswere prepared as KBr disks or run neat, as indicated. Abbreviationsused to describe the peak intensities are: vs (very strong), s(strong), m (medium), w (weak), sh (shoulder) and br (broad). Allmass spectrometry was performed using a Micromass Platform II,with an ESI source. The capillary voltage was 3.5 eV and the conevoltage 35 V unless otherwise noted. Compounds were dissolvedin an organic solvent and ionized using an electrospray ionizationsource (ESI). Ion peaks were compared with expected monoiso-topic masses. Column chromatography was performed using silicagel (60 mesh) from Merck. The solvent used for elution varieddepending on the compound of interest. Microanalyses were per-formed by the Campbell Microanalytical Service, University ofOtago, New Zealand. Electronic spectra were recorded on a Cary5G UV–Vis–NIR spectrophotometer in 1 cm quartz cells.

2.2. Synthesis

2.2.1. 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-1,4,7-triazacyclononane, 5, (L1)2.2.1.1. 2-(4-aminophenyl)benzothiazole, 1. 2-(4-Aminophenyl)ben-zothiazole 1 and N-(40-benzothiazol-2-yl-phenyl)-2-chloroacet-amide 2, were synthesized as reported previously with somemodifications [18]. For 1, 40 ml of polyphosphoric acid were placedin a 250 mL round bottom flask and heated to 150 �C. In the mean-time, p-aminobenzoic acid (9.59 g, 70.0 mmol) was transferredinto the flask in aliquots and the contents were stirred to dissolvethe aminobenzoic acid. A thick pasty brown mass was obtainedafter the complete addition of the acid. To this mixture was added

o-aminothiophenol (8.75 g, 70.0 mmol) whereupon a vigorousreaction took place and the mixture turned into a black viscousmass. The contents were heated to 220 �C for 9 h, cooled to100 �C and then carefully poured into a beaker containing ice/water mixture. The oily product thus obtained slowly solidifiedupon standing (2 h) and the mixture was allowed to stir to obtaina light yellow product. This was filtered and washed with water(2 � 100 mL). The precipitate was then suspended in a solutionof sodium bicarbonate (50 g/500 ml of water) and stirred vigor-ously for 2 h. A light greenish product remained in suspensionwhich was filtered, washed with water (2 � 100 mL) and driedunder vacuum for 48 h. The product was further purified byre-crystallization using methanol to yield dark yellow needles of2-aminophenylbenzothiazole 1. Yield: 8.00 g, 35.2 mmol, 50%.Selected IR bands m (cm�1) (KBr pellet): 3429s, 3178s, 1636s,1604m, 1475s, 1433m, 1312m, 1250m, 1228m, 1182m, 1159m,963m, 827s, 760s. 1H NMR (400 MHz) (d6-DMSO), d ppm: 8.02–7.98 (m, 2H), 7.77–7.73 (d, 2H, J = 8.0 Hz), 7.45–7.44 (t, 1H),7.36–7.31 (t, 1H), 6.69–6.65 (d, 2H, J = 8.0 Hz), 5.89 (s, 2H); ESIMS (+ mode): calculated: 226, found: 227 [M+H]+.

2.2.1.2. N-(40-benzothiazol-2-yl-phenyl)-2-chloroacetamide, [18] 2. Ina 250 mL round bottom flask was placed 2-(4-aminophenyl)benzo-thiazole (2.36 g, 10.3 mmol) and 60 mL of anhydrous methylenechloride. The contents were stirred; however, the solid did notcompletely dissolve at this stage. Using a dry syringe, 2 mL of tri-ethylamine was introduced into the flask and the solutionbecame homogenous dissolving the benzothiazole compound. Tothe clear solution, chloroacetylchloride (1 mL) was slowly added,causing a vigorous exothermic reaction and the evolution of fumesduring the course of addition. A white insoluble precipitate formedin the flask on stirring for 48 h, which was collected by filtration,washed with ether and dried in vacuum (1.20 g). The filtrate wastreated with 20 mL of 5 M HCl, the organic layer separated, driedover anhydrous sodium sulfate and subsequently filtered. Removalof solvent left a residue which was triturated with 50 mL of diethylether. The insoluble material was filtered and dried in vacuum toyield 0.80 g of a brown colored powder. Both solids were re-crys-tallized in 96% ethanol, resulting in a combined yield of 2.00 g,64%. The NMR spectrum confirmed both products to be compound2. Selected IR bands m (cm�1) (KBr pellet): 3317s, 1675vs, 1599s,1528s, 1482m, 1435m, 1409m, 1314m, 1285m, 1252m, 1228m,1192m, 1116m, 963m, 846m, 828m, 754s. 1H NMR (400 MHz)(d6-DMSO), d ppm: 10.76 (br, 1H), 8.10–7.98 (m, 4H), 7.80–7.78(d, 2H, J = 8.0 Hz), 7.52–7.50 (t, 1H), 7.43–7.40 (t, 1H), 4.25 (s,2H). 13C NMR (100 MHz) (d6-DMSO), d ppm: 167.4, 165.7, 154.7,141.9, 134.9, 128.7, 127.2, 125.9, 123.2, 122.9, 120.2, 44.2. ESIMS (+mode): calculated: 302.5 [M+], found: 303 [M+H+].

2.2.1.3. 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-4,7-diaza-1-azoniatricyclo[5.2.1.04,10]decane chloride, 3. In a 100 mL roundbottom flask was placed 2 (0.60 g, 2.0 mmol), anhydrous acetoni-trile (30 mL) followed by a solution of 1,4,7-triazacyclo[5.2.1.04,10]-decane, 6, (0.67 g, 4.6 mmol) dissolved in 20 mL of acetonitrile. Thecontents were heated to reflux. After 3 h of heating an insolubleprecipitate appeared in the mixture. Heating at reflux was contin-ued for 48 h whereupon the mixture was cooled to room temper-ature. The precipitated orthoamidinium salt was filtered, washedwith diethyl ether and dried to give a white powder. Yield:0.80 g, 1.8 mmol, 40%.

2.2.1.4. 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-2-formyl-1,4,7-triazacyclononane, 4. In a 50 mL round bottom flask wasplaced 3 (0.70 g, 1.6 mmol) and 15 mL of water. The mixture wasrefluxed for 4 h, cooled to room temperature and then evaporatedto remove water. The residue was dissolved in 100 mL of

130 J. Barreto et al. / Polyhedron 52 (2013) 128–138

chloroform and the solution was washed with 20 mL of 3 M NaOH.The organic layer was separated, dried over anhydrous sodium sul-fate and filtered. Rotary evaporation of the solvent gave a viscousoily residue which slowly solidified on standing. Yield: 0.52 g,1.20 mmol, 75%.

2.2.1.5. 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-1,4,7-tri-azacyclononane, 5, (L1). In a 100 mL round bottom flask was placed4 (0.40 g, 0.90 mmol) and 15 mL of methanol was added followedby 10 mL of 5 M HCl. The contents were stirred at room tempera-ture for 48 h and the solvents removed on a rotary evaporator.The residue was dissolved in 1 mL of water and solid sodiumhydroxide pellets (60 mg) were carefully added until the pH was>13. A precipitate was visible in the flask which dissolved on addi-tion of 20 mL of chloroform. The chloroform layer was separatedfrom the aqueous layer and dried over anhydrous sodium sulfate.Filtration and removal of the solvent on a rotary evaporator gavea light yellowish solid. Yield of L1: 0.30 g, 0.74 mmol, 82%. SelectedIR bands m (cm�1) (KBr pellet): 3316br, 2918s, 2804m, 1663vs,1588s, 1538s, 1477s, 1436m, 1407m, 1368m, 1351m, 1305m,1260m, 1228m, 1172m, 1138m, 1036m, 972m, 844m, 756s. 1HNMR (300 MHz, CDCl3) d ppm: 11.39 (s, 1H), 8.05–8.03 (d, 3H,J = 6.0 Hz), 7.90–7.79 (m, 3H), 7.50–7.45 (t, 1H), 7.39–7.34 (t, 1H),3.44 (s, 2H), 2.96–2.73 (m, 12H), 1.94-(bs, 2H) 13C NMR (75 MHz,CDCl3) d ppm: 47.21, 48.41, 54.94, 61.66, 120.14, 121.87, 123.24,125.27, 126.56, 128.53, 128.58, 128.61, 129.25, 129.34, 135.25,141.63, 154.50, 167.99, 171.37; ESI MS (+ mode): calculated 395[M+]; found 396 [M+H+]. Elemental analysis: found C 56.27, H5.42, N 14.83, S 7.01%; calculated for C21H25N5OS.NaCl C 55.56, H5.55, N 15.43, S 7.06%.

2.2.2. 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-4-(2-pyridyl-methyl)-1,4,7-triazacyclononane, 10, (L2)2.2.2.1. 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-4-(2-pyri-dylmethyl)-7-formyl-1,4,7-triazacyclononane, 9. This synthesis wasaccomplished using 1-(2-pyridylmethyl)-4-formyl-1,4,7-triazacy-clononane 8, which was prepared following the proceduredescribed by Gasser et al. [1] as shown in Scheme 2. Compound8 (1.24 g, 5.00 mmol) was loaded into a 100 mL round bottom flaskand 50 mL of anhydrous acetonitrile were added. The mixture wasstirred and compound 2 (3.00 g, 9.90 mmol) was added followedby anhydrous potassium carbonate (3.00 g) and potassium iodide(0.60 g). The contents were stirred and the solution was refluxedfor 5 days. After this period, the mixture was cooled to room tem-perature and filtered. The insoluble precipitate was further washedwith 2 � 10 mL of acetonitrile. The acetonitrile solutions werecombined and reduced in volume on a rotary evaporator to yielda viscous residue which was dissolved in 100 mL of chloroformand washed with 2 � 10 mL of 3 M NaOH. The organic layer wasseparated from the aqueous layer and dried over anhydrous so-dium sulfate. Filtration and rotary evaporation of the solvent gavean oily residue of 9. Yield: 1.01 g, 1.90 mmol, 38%.

2.2.2.2. 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-4-(2-pyri-dylmethyl)-1,4,7-triazacyclononane, 10 (L2). Compound 9 (0.70 g,1.35 mmol) and 10 mL of methanol were added to a round bottomflask and the mixture stirred at room temperature whilst hydro-chloric acid (5 M, 15 mL) was added. Stirring was continued for48 h whereupon the solvent was removed under vacuum. Theresidue was dissolved in minimum amount of water (1.5 mL) andsodium hydroxide pellets (0.08 g) were added. The precipitatedproduct was extracted with 40 mL of chloroform and the organiclayer was separated from the aqueous layer and dried over anhy-drous sodium sulfate. Filtration and evaporation of the solventyielded the desired product as a foamy light yellow solid. Yield:0.54 g, 1.10 mmol, 81%. Selected IR bands m (cm�1) (KBr disc):

3173br, 2929s, 2825m, 1677vs, 1592s, 1533s, 1482s, 1313m,1177m, 908m, 731s. 1H NMR (300 MHz, CDCl3), d ppm: 10.99 (s,1H), 8.52–8.51 (br, 1H, J = 3.0 Hz), 8.03–7.99 (m, 3H), 7.87–7.85(d, 1H, J = 6.0 Hz), 7.81–7.78 (d, 2H, J = 9.0 Hz), 7.57–7.51 (m, 1H),7.49–7.43 (m, 1H), 7.37–7.31 (m, 1H), 7.22–7.19 (d, 1H,J = 9.0 Hz), 7.15–7.10 (m, 1H), 3.88 (s, 2H), 3.42–3.38 (m, 2H),3.10–2.60 (m, 10H), 13C NMR (50 MHz, CDCl3), d ppm: 47.05,47.92, 54.05, 54.80, 54.97, 55.54, 61.73, 62.60, 120.08, 121.73,122.31, 123.05, 123.44, 125.12, 126.40, 128.40, 128.94, 135.05,136.52, 141.63, 149.28, 159.07, 167.77, 171.50. ESI MS (+ mode):calculated 486 [M+]; found 487 [M+H+], 509 [M+Na+]. Elementalanalysis: found C 59.01, H 5.54, N 15.09, S 5.81%; calculated for C27-

H30N6OS.NaCl: C 59.49, H 5.55, N 15.42, S 5.88%.

2.2.3. 1-(2-(4-N-methylaminophenyl)benzothiazolyl)-2-oxoethyl)-4-(2-pyridylmethyl)-1,4,7-triazacyclononane, 14, (L3)2.2.3.1. 2-(4-N-methylaminophenyl) benzothiazole, 11. 2-(4-N-methylaminophenyl)benzothiazole, 11, and N-(40-benzothiazol-2-yl-phenyl)-methyl-2-chloroacetamide 12, were synthesizedfollowing a similar procedure as for compounds 1 and 2. For 11,polyphosphoric acid (60 mL) was placed in a 250 mL round bottomflask and heated to 150 �C. In the meantime, N-methyl-p-amino-benzoic acid (12.00 g, 79.47 mmol) was transferred into the flaskin aliquots and the contents were stirred to dissolve theN-methyl-p-aminobenzoic acid. To the thick pasty brown massobtained after addition of the acid, o-aminothiophenol 10.00 g(80.00 mmol) was added whereupon a vigorous reaction took placeand the mixture turned into a black viscous mass. The contentswere heated to 220 �C for 9 h and cooled to 100 �C and carefullypoured into a beaker containing an ice/water mixture. The oilyproduct thus obtained slowly solidified upon standing (2 h). Themixture was stirred to obtain a light yellow product. This was fil-tered and washed with water (2 � 100 mL). The precipitate wasthen suspended in a solution of sodium bicarbonate (50 g/500 mlof water) and stirred vigorously for 2 h to obtain a light greenishproduct. This was filtered and, washed with water (2 � 100 mL)and dried under vacuum for 48 h. The product was further purifiedby column chromatography on silica gel using 1% methanol indichloromethane as eluent to yield 2-(4-N-methylaminophe-nyl)benzothiazole, 11, as a green powder. Yield: 3.02 g, 12.6 mmol16%. Selected IR bands m (cm�1) (KBr pellet): 3487br, 3307vs,2925m, 1607vs, 1512m, 1464s, 1439s, 1415m, 1341s, 1225m,1180s, 961m, 822m, 757s. 1H NMR (200 MHz) (CDCl3), d ppm:7.80–8.00 (m, 4H), 7.25–7.60 (m, 2H), 6.60–6.67 (m, 2H), 4.14 (s,br, 1H), 2.89 (s, 3H); ESI MS (+ mode): calculated 240; found 241[M+H]+.

2.2.3.2. N-(40-benzothiazol-2-yl-phenyl)-methyl-2-chloroacetamide,12. 2-(4-N-methylaminophenyl)benzothiazole (1.00 g, 4.16 mmol)was placed in a 250 mL round bottom flask, and anhydrous meth-ylene chloride (60 mL) was added. The contents were stirred, how-ever, the solid did not fully dissolve at this stage. Using a drysyringe, triethylamine (1 mL) was introduced into the flask fullydissolving the benzothiazole derivative. To the clear solution, chlo-roacetylchloride (1 mL) was slowly added, resulting in a vigorousexothermic reaction and the development of fumes. On stirringfor 48 h, a white precipitate appeared in the flask, which was col-lected by filtration, washed with diethyl ether and dried in vacuum(0.38 g). The filtrate was treated with 20 mL of 5 M HCl, the organiclayer separated and dried over anhydrous sodium sulfate and sub-sequently filtered. Removal of solvent left a residue, which wastriturated with 50 mL of diethyl ether and the insoluble materialcollected by filtration and dried in vacuum to yield 0.30 g of browncolored powder. Combined yield: 0.68 g, 2.15 mmol, 52%. An NMRspectrum confirmed both samples to be compound 12. Selected IRbands m (cm�1) (KBr pellet): 3317br, 1675s, 1599s, 1528m, 1482s,

J. Barreto et al. / Polyhedron 52 (2013) 128–138 131

1435m, 1409m, 1314m, 1285m, 1252m, 1228m, 1192m, 1116m,963m, 846m, 828m, 754s. 1H NMR (200 MHz) (CDCl3), d ppm:7.90–8.30 (m, 4H), 7.80–7.78 (m, 4H), 3.93 (s, 2H), 3.38 (s, 3H).13C NMR (50 MHz) (CDCl3), d ppm: 168.4, 165.8, 154.6, 143.9,133.9, 128.8, 126.4, 125.5, 124.2, 122.3, 120.9, 43.2, 35.4. ESI MS(+mode): calculated 316 [M+]; found: 317 [M+H+].

2.2.3.3. 1-(2-(4-N-methylaminophenyl)benzothiazolyl)-2-oxoethyl)-4-(2-pyridylmethyl)-7-formyl-1,4,7-triazacyclononane, 13. 1-(2-Pyridyl-methyl)-4-formyl-1,4,7-triazacyclononane, 8, (0.87 g, 3.50 mmol)was added to a 100 mL round bottom flask followed by 30 mL ofanhydrous acetonitrile. Whist stirring compound 12 was added(1.10 g, 3.50 mmol) followed by anhydrous potassium carbonate(2.00 g) and potassium iodide (0.02 g). The mixture was refluxedfor 3 days, cooled to room temperature and filtered. The insolubleprecipitate was washed with 2 � 10 mL of acetonitrile and the sol-vent removed from the combined acetonitrile solutions on a rotaryevaporator to yield an oily product. This was purified by columnchromatography on silica gel with dichloromethane:methanol10:1 as eluent, yielding a reddish oil, on evaporation of the solvent.Yield: 1.42 g, 2.59 mmol, 74%. Selected IR bands m (cm�1) (KBr disc):3449m br, 3052m, 2923m, 2854m, 1664vs, 1604s, 1484s, 1435s,1370s, 1314s, 1266m, 1121m, 968m, 731s. 1H NMR (200 MHz,CDCl3), d ppm: 8.45 (m, 1H), 7.90–8.20 (m, 4H), 7.85 (m, 1H),7.55–7.65 (m, 1H), 7.10–7.49 (m, 4H), 6.95–7.15 (m, 1H), 3.75–4.25 (m, 4H), 3.05–3.68 (m, 12H), 2.45–3.05 (m, 4H), 13C NMR(50 MHz, CDCl3), d ppm: 37.32, 46.55, 47.30, 50.27, 52.96, 52.97,53.78, 57.86, 63.29, 121.84, 122.39, 123.21, 123.61, 125.65, 126.64,127.41, 128.42, 135.02, 136.86, 137.02, 145.30, 148.75, 149.05,153.91, 164.10, 166.61, 170.86. ESI MS (+ mode): calculated 528;found 529 [M+H+].

2.2.3.4. 1-(2-(4-N-methylaminophenyl)benzothiazolyl)-2-oxoethyl)-4-(2-pyridylmethyl)-1,4,7-triazacyclononane, 14 (L3). In a roundbottom flask was placed 13 (1.42 g, 2.59 mmol) and 25 mL ofmethanol. The mixture was stirred at room temperature until dis-solution. Hydrochloric acid (5 M, 25 mL) was added and the solu-tion was stirred at room temperature for 3 days. The solvent wasremoved under vacuum and the residue was dissolved in mini-mum amount of water (3 mL) and NaOH pellets (0.08 g) wereadded. A precipitate formed on addition of the base which was ex-tracted with 40 mL of chloroform. The organic layer was then sep-arated from the aqueous layer and dried over anhydrous sodiumsulfate. Filtration and evaporation of the solvent isolated the de-sired product, 14, as a red solid. Yield: 1.28 g, 2.56 mmol, 99%. Se-lected IR bands m (cm�1) (KBr disc): 3386m br, 3061w, 2911s,2861s, 1663vs, 1605s, 1592m, 1484s, 1435s, 1381w, 1314m,1120m, 968m, 909m, 729vs. 1H NMR (300 MHz, CDCl3), d ppm:8.42 (d, 1H), 8.18–8.00 (m, 3H), 7.98–7.70 (m, 1H), 7.58–7.20 (m,7H), 7.08–6.95 (m, 1H), 3.83 (s, 2H), 3.42–3.10 (m, 5H), 2.92–2.45(m, 11H), 13C NMR (50 MHz, CDCl3), d ppm: 37.65, 46.83, 47.25,50.45, 53.05, 52.90, 53.85, 57.93, 63.18, 121.75, 122.56, 123.31,123.65, 125.70, 126.61, 127.45, 128.48, 135.10, 136.95, 137.45,145.33, 148.78, 149.06, 153.95, 166.66, 170.90. ESI MS (+ mode):Calculated: 500 [M+], found: 501 [M+H+]. Elemental analysis:found C 54.66, H 5.91, N 13.57, S 5.68%; calculated for C28H32N6-

OS.2NaCl C 54.46, H 5.22, N 13.61, S 5.19%.

2.2.4. 1,4-bis(2-pyridylmethyl)-7-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-1,4,7-triazacyclononane, 17 (L4)

Compound 2 (0.80 g, 3.29 mmol) was placed in a 100 mL roundbottom flask together with 30 mL of anhydrous acetonitrile. Themixture was stirred and a solution of 16 (0.81 g, 2.62 mmol) dis-solved in 20 mL of acetonitrile was added. The mixture was stirrredfor 10 min before the addition of 2.00 g of anhydrous potassiumcarbonate and 0.50 g of potassium iodide. After refluxing the

contents of the flask for 72 h, the mixture was cooled and filtered.The insoluble precipitate was further washed with 2 � 10 mL ofacetonitrile and the combined acetonitrile fractions were evapo-rated to dryness. The residue thus obtained was dissolved in100 mL of chloroform and washed with NaOH (5 M, 2 � 10 mL).The organic layer was separated from the aqueous layer and driedover anhydrous sodium sulfate. Filtration followed by rotary evap-oration of the solvent gave 17 as a light brownish solid. Yield:0.58 g, 1.00 mmol, 38%. Selected IR bands m (cm�1) (KBr pellet):2924s, 1678s, 1588s, 1532m, 1482m, 1434m, 1409m, 1311m,1251m, 1226m, 1175m, 1048m, 966m, 841m, 757s cm�1; 1HNMR (300 MHz, CDCl3) d ppm: 10.91 (s, 1H), 8.50–8.48 (d, 2H,J = 6.0 Hz), 8.0–7.98 (m, 3H), 7.88–7.78 (m, 3H), 7.56–7.42 (m,3H), 7.37–7.31 (m, 2H), 7.21–7.09 (m, 3H), 3.87 (s, 4H), 3.31 (s,2H), 2.99–2.68 (m, 12H); 13C NMR (50 MHz, CDCl3), d ppm: 54.5,55.3, 55.8, 62.8, 63.9, 119.2, 120.3, 121.0, 121.8, 124.0, 124.6,125.3, 126.8, 129.1, 133.8, 138.7, 139.8, 148.5, 154.8, 157.8,168.3, 169.7. ESI MS (+ mode): calculated 579 [M+]; found 580[M+H+]. Elemental analysis: found C 56.46, H 5.23, N 13.60, S5.19%; calculated for C33H35N7OS.2NaCl C 57.06, H 5.08, N 14.12,S 4.62%.

2.2.5. [Cu(L1)(OH2)(ACN)](ClO4)2�0.5ACN (C1)L1 (50 mg, 0.13 mmol) was dissolved in 1 mL of acetonitrile. A

solution of Cu(ClO4)2�6H2O (37 mg, 0.13 mmol) in 1 mL of acetoni-trile was added whereupon a dark green solution was formed. Suit-able crystals for X-ray analysis were obtained on diffusion ofdiethyl ether into the acetonitrile solution of the complex. Yield:51 mg, 0.067 mmol, 53%. IR (ATR in KBr, m in cm�1): 3504s,3284m, 2927m, 2887m, 1627s, 1599vs, 1560s, 1483m, 1438m,1323m, 1110vs, 766m, 625s. Solution UV–Vis (k (nm), e (M�1 -cm�1)): 650 (29), 312 (18200), 208 (22500). Diffuse reflectance (k(nm)): 646 nm. Elemental analysis: found C 40.01, H 4.15, N12.25%; calculated for C23H28Cl2CuN6O9S C 39.52, H 4.04, N 12.02%.

2.2.6. [Cu(L3)](ClO4)2�ACN (C2)L3 (50 mg, 0.10 mmol) was dissolved in 1 mL of acetonitrile. A

solution of Cu(ClO4)2�6H2O (27 mg, 0.10 mmol) in 1 mL of acetoni-trile was added resulting in a dark green solution. Suitable crystalsfor X-ray analysis were obtained as in the case of C1. Yield: 48 mg0.060 mmol, 60%. IR (ATR in KBr, m in cm�1): 3449s, 3333s, 3068m,2936m, 1616s, 1593vs, 1482m, 1447m, 1315w, 1292w, 1088vs,762m, 624s. Solution UV–Vis (k (nm), e (M�1 cm�1)): 615 (32),305 (17400), 257 (11600), 205, (35000). Diffuse reflectance (k(nm)): 595 nm. Elemental analysis: found C 40.26, H 4.33, N9.96%; calculated for C28H40Cl2CuN6O13S C 40.27, H 4.83, N 10.06%.

2.2.7. [Cu(L4)](ClO4)2�0.5THF (C4)L4 (0.17 g, 0.24 mmol) was dissolved in a mixture of THF and

acetonitrile (5 ml of each) and solid Cu(ClO4)2�6H2O (0.087 g,0.24 mmol) was added. The dark green solution was reduced involume to 5 mL by rotary evaporation. Slow evaporation of thissolution gave pale blue crystals suitable for X-ray analysis. Yield:43 mg, 0.05 mmol, 22%. IR (ATR in KBr, m in cm�1): 3423s br,1671s, 1600s, 1542s, 1481m, 1438m, 1315m, 1147s, 1114vs,1088vs, 766m, 625s. Solution UV–Vis (k (nm), e (M�1 cm�1)): 690(25), 320 (16500), 259 (12100), 200 (35500). Elemental analysis:found C 35.45, H 3.63, N 8.71%; calculated for C33H44Cl9CuN7O10SC 35.60, H 3.98, N 8.81%.

2.3. X-ray structure Determinations

Single crystals were mounted on thin glass fibers. X-ray crystal-lography data were obtained on a Nonius Kappa CCD or BrukerApex II CCD (C2) with monochromated Mo� Ka radiation(k = 0.71073 Å) at 123(2) or 173 (2) (C1) K using phi and/or omega

Table 1Crystallographic data for C1, C2 and C4.

C1 C2 C4

Crystal dataChemical formula C24H33.5N6.5O11SCl2Cu C30H35N7O9SCl2Cu C70H78N14O19S2Cl4Cu2

M (g/mol) 755.57 804.15 1752.46Crystal system triclinic orthorhombic monoclinicSpace group P�1 P212121 P21/ca (Å) 7.67000(10) 8.7319(7) 8.0231(16)b (Å) 9.0231(2) 9.1285(9) 25.399(5)c (Å) 25.2426(7) 42.461(4) 19.103(4)a (�) 98.62(10) 90 90b (�) 91.73(10) 90 99.23(3)c (�) 112.44(10) 90 90Volume (Å3) 1589.12(6) 3384.6(5) 3842.4(13)Z 2 4 2Dc (Mg m�3) 1.579 1.578 1.515h range (�) 1.64–30.00� 2.38–27.50� 1.34–25.00�Data collection method Phi and omega scans Phi and omega scans Phi and omega scansAbsorption corrections Multi-scan (SORTAV) Multi-scan (SADABS) Multi-scan (SORTAV)Reflections collected 22349 25553 35348Unique reflections (Rint) 8947 (0.0519) 7779 (0.0666) 6726 (0.1512)Goodness-of-fit on F2 1.039 1.049 1.038F(000) 780 1660 1812Rint 0.0519 0.0843 0.1512R1

a, wR2b [I > 2r(I)] 0.0554, 0.1280 0.0598, 0.1171 0.0838, 0.1968

Largest diff. peak and hole (e �3) 0.464, �0.587 0.545, �0.548 0.680, 1.411

a R1 = R||F0| � |Fc||/R|F0|.b wR2 = [Rw(F0

2 � Fc2)2/Rw(F0

2)2]1/2.

132 J. Barreto et al. / Polyhedron 52 (2013) 128–138

scans. The absorptions have been corrected by semi-empirical ap-proach using the SORTAV or SADABS software [19,20]. The structureswere solved by direct method and refined by full matrix leastsquares using SHELX-97 software [21,22]. The program X-Seed[23] was used as an interface to the SHELX programs and to pre-pare the figures. All hydrogen atoms were placed in idealized posi-tions, except for the hydrogens on the nitrogen atoms and theoxygen atoms of the water molecules, which were located on theFourier difference map and refined with restrained N–H and O–Hdistances. The isotropic thermal parameters for N–H and O–Hhydrogen atoms were fixed at 1.2 times that of the respectivenitrogen or oxygen atom. The perchlorate counteranions in C1were found disordered and refined anisotropically using part com-mand. Where applicable, # indicates symmetry-generated atoms.For C4, the tetrahydrofuran molecule was disordered over aninversion centre. The high residual peaks between 1.41 and 2.09represent part of the disorder. Crystallographic data for C1, C2and C4 are presented in Table 1.

3. Results and discussion

3.1. Synthesis and characterization of ligands

The synthesis of 5 was achieved following the protocol de-scribed in Scheme 1 from 1,4,7-triazacyclo[5.2.1.04,10]decane, 6.First, 2-(4-aminophenyl)benzothiazole, 1,[18] was prepared andreacted with chloroacetylchloride to yield N-(40-benzothiazol-2-yl-phenyl)-2-chloroacetamide, 2,[18] which crystallized from eth-anol as white-yellowish crystals. Formation of the product wasconfirmed by 1H NMR which shows the appearance of a peak at4.26 ppm corresponding to the methylene protons of the chloro-acetamide. Condensation of 6 with 2 gave 4 which was convertedto the formyl derivative by refluxing in water. Deprotection usinghydrochloric acid at room temperature furnished the requiredmono aminophenylbenzothiazole substituted tacn derivative 5(L1) in 60% yield as a light yellow foam. Formation of the monosub-stituted product was confirmed by mass spectrometry which only

shows a peak corresponding to the parent ion (m/z = 395, M+H+),and by elemental analysis.

The synthesis of 10 (L2) and 14 (L3) was achieved following theprocedures outlined in Schemes 2 and 3. For L2, reaction of 2-pic-olylchloride with 6 followed by hydrolysis generates the formylderivative, 8, [1] which was further condensed with 2 to producecompound 9, which was deprotected in acid to give L2. For L3, asimilar procedure was implemented in which the meth-ylatedbenzothiazole derivative, 2-(4-N-methylaminophenyl)ben-zothiazole, 11, produced following a similar procedure as for 1,was converted into the chloroacetamide derivative of 12 by con-densation with chloroacetylchloride. Reaction of 12 with 8 yielded13, which was further hydrolyzed in acid to obtain L3. Formation ofthe compounds was confirmed by mass spectrometry which showsa unique parent peak at 487 and 501 (M+H+), respectively.

Compound 17, L4 (Scheme 4) was obtained by alkylation ofdmptacn, 16, itself prepared following the procedure of Gasseret al. [1] Formation of the benzothiazole derivative was confirmedby 1H NMR spectroscopy, which shows a shift in the position of themethylene protons signal in the chloroacetamide derivative from4.26 ppm to 3.31 ppm due to attachment to a nitrogen of the tacnring, and by observation of the parent peak at 580 (M+H+) in themass spectrum.

Crystals of the copper (II) complexes of L1, L3 and L4 were ob-tained either by ether diffusion into an acetonitrile solution (C1and C2) or by slow evaporation of a solution of the complex (C3).The complexes were characterized by IR spectroscopy, UV–Vis.spectrophotometry and elemental analysis. The complexes exhibitbands around 610–690 nm in the visible spectrum recorded in ace-tonitrile, which are characteristic of copper(II) complexes in eithera square pyramidal or a tetragonally distorted octahedral geome-try, for which dz2 ! dx2 � dy2 and dyz dxz ! dx2 � dy2 transitionsare expected, rather than trigonal bipyramidal [24,25]. As for C1–C3, UV–Vis analysis of a solution of the copper(II) complex of L2,formed in situ by reacting equimolar amounts of L2 and Cu(ClO4)2-

�6H2O, revealed a band at 618 nm (28 M�1 cm�1) similar to thoseobserved for C2 {efforts to prepare the Cu(II)–L2 complex wereunsuccessful}. Square pyramidal complexes typically exhibit a

Scheme 1.

Scheme 2.

J. Barreto et al. / Polyhedron 52 (2013) 128–138 133

weaker transition in the 900–1100 nm region. This was not ob-served for the complexes reported herein indicating that the geom-etry adopted by C2 and C4 in solution may be different to thatobtained by X-ray crystallography. The diffuse reflectance spectraof the complexes in solid state confirmed the absence of a bandin the 900–1100 nm region for C1 supporting the octahedral natureof the complex. In the case of C2, a weak band around 1050 nmsupports the adoption of a square pyramidal geometry by the com-plex in the solid state.

3.2. X-ray crystal structure determinations

3.2.1. [Cu(L1)(OH2)](ClO4)2�0.5ACN (C1)The asymmetric unit of C1 comprises of one [Cu(L1)(H2O)(CH3-

CN)]2+ complex cation, two perchlorate anions, one water and anacetonitrile molecule of crystallization. One acetonitrile ligand

binds weakly to the Cu(II) centre. As a consequence, the geometryaround the Cu(II) centre in C1 may be described as pseudo-octahedral with a strong Jahn–Teller distortion along the z axis.The coordination sphere for copper(II) consists of three faciallycoordinating nitrogen atoms of the tacn ring (N1–N3), carbonyloxygen O1 from the pendant benzothiazole arm (Cu1–O1 = 1.9759(19) Å), oxygen atom O2 from a water molecule(Cu1–O2 = 1.972(2) Å), and a weakly coordinating nitrogen (N5)from an acetonitrile molecule with the corresponding Cu–N bondlength of 2.681 Å (Fig. 1). The Cu–N bond distances (av. 2.089 Å)and the N–Cu–N bond angles for copper(II) coordination to themacrocyclic nitrogens are in agreement to those generally ob-served in Cu(II)–tacn derivatives (Table 2) [26,27].

As illustrated in Fig. 2, the crystal structure shows an anti-par-allel p� � �p stacking of the cations, which is stabilized by extensiveintermolecular H-bonding interactions within the lattice space

Scheme 3.

Scheme 4.

134 J. Barreto et al. / Polyhedron 52 (2013) 128–138

Fig. 1. Thermal ellipsoid representation of the cationic unit in C1 showing thepseudo-octahedral geometry around the Cu(II) centre (ellipsoids drawn at 30%probability; selected hydrogen atoms, non-coordinating solvent molecule and thecounter anions have been omitted for clarity; dashed bonds indicate weak bondinginteractions).

Table 2Selected bond distances (Å) and angles (�) for C1.

Cu(1)–O(2) 1.972(2) O(1)–Cu(1)–N(1) 168.71(10)Cu(1)–O(1) 1.9759(19) O(2)–Cu(1)–N(3) 173.50(10)Cu(1)–N(1) 2.001(3) O(1)–Cu(1)–N(3) 83.78(8)Cu(1)–N(3) 2.029(2) N(1)–Cu(1)–N(3) 86.17(11)Cu(1)–N(2) 2.237(3) O(2)–Cu(1)–N(2) 100.92(12)

O(1)–Cu(1)–N(2) 101.11(10)O(2)–Cu(1)–O(1) 91.42(10) N(1)–Cu(1)–N(2) 82.97(12)O(2)–Cu(1)–N(1) 98.18(12) N(3)–Cu(1)–N(2) 84.35(11)

Table 3Hydrogen bonds for C1 [Å and �].

D–H. . .A d(D–H) d(H. . .A) d(D. . .A) \(DHA)

N(9)–H(9N). . .O(3)#1 0.868(19) 1.93(2) 2.795(3) 176(4)N(1)–H(1N). . .O(5) 0.878(19) 2.03(2) 2.873(8) 161(4)N(1)–H(1N). . .O(10) 0.878(19) 2.31(2) 3.186(9) 172(4)N(2)–H(2N). . .O(10)#2 0.886(19) 2.15(2) 3.019(7) 166(4)N(2)–H(2N). . .O(5)#2 0.886(19) 2.52(3) 3.295(10) 146(3)O(2)–H(4O). . .O(11) 0.875(19) 2.20(3) 2.881(8) 134(4)O(2)–H(4O). . .N(6) 0.875(19) 1.88(2) 2.717(7) 159(4)O(2)–H(3O). . .O(13) 0.833(18) 2.49(3) 3.161(12) 138(4)O(2)–H(3O). . .O(18) 0.833(18) 2.24(3) 3.033(9) 159(4)O(2)–H(3O). . .O(19) 0.833(18) 1.84(4) 2.59(3) 149(4)O(3)–H(2O). . .N(4)#3 0.871(19) 2.033(19) 2.904(3) 177(4)O(3)–H(1O). . .O(17) 0.854(19) 2.19(2) 2.989(5) 156(4)O(3)–H(1O). . .O(16) 0.854(19) 2.08(3) 2.865(13) 153(4)

Symmetry transformations used to generate equivalent atoms: #1 x + 1, y + 1, z ; #2x + 1, y, z; #3 x � 1, y, z.

J. Barreto et al. / Polyhedron 52 (2013) 128–138 135

(Table 3). These interactions arise due to the water molecules andthe perchlorate anions co-existing within the crystal lattice. Stabil-ization of such interactions occurs due to the fact that the watermolecules coordinate to the metal center while simultaneouslyhydrogen bonding with the perchlorate oxygen atoms. These per-chlorate molecules serve as bridge by H-bonding to second watermolecule which in turn is linked to the aromatic nitrogen of thebenzothiazole moiety via a H-bond (O(3)–H(2O). . .N(4), 2.904 Å,#3 denoting the symmetry operator: x � 1, y, z).

3.2.2. [Cu(L3)](ClO4)2ACN (C2)C2 consists of [Cu(L3)]2+ complex cation, two perchlorate

counteranions and a non-coordinating acetonitrile molecule. The

Fig. 2. Stick diagram showing a segment of the anti-parallel p� � �p interstacked linear chcationic units, co-crystallized water molecules and perchlorate counter anions presinteractions).

molecular structure together with the atom numbering scheme isdepicted in Fig. 3. Fig. 4 shows the H-bonding interactions betweenthe components of the unit cell and p. . .p interactions between thearomatic rings of the benzothiazole pendant group. Selected bondparameters and the hydrogen bonding characteristic for the mole-cule are listed in Table 4. The Cu(II) centre is in a distorted squarepyramidal geometry where the metal atom is centered in the baseof the pyramid defined by atoms N1, N2, N4 and O1. The axialnitrogen (N3) is inclined towards one face of the pyramid formingN–Cu–N angles of 83.47(15) and 84.08(15)� with the nearest donoratoms (N1 and N2) while moving away from the opposite face ofthe pyramid, exhibiting more obtuse N(3)–Cu(1)–O(1) and N(3)–Cu(1)–N(1) angles (106.19(15) and 117.80(15)�, respectively).The Addison equation [28], s = (b � a)/60, where b is the larger ofthe two largest angles can be employed to further analyze the cop-per(II) geometry. An ideal square pyramid will have a distortionparameter s of 0 since both angles, a and b should be 180�, but atrigonal bipyramidal structure will have s of 1 (b = 180� anda = 120�). The s value in this case is 0.17 indicating that the com-plex is close to a square pyramidal geometry with only slight devi-ation towards a trigonal bipyramidal geometry.

3.2.3. [Cu(L4)](ClO4)2�0.5THF (C4)The asymmetric unit of C4 contains the complex cation, two

perchlorate anions and a disordered tetrahydrofuran molecule.

ains, formed due to extensive intermolecular H-bonding interactions between theent in the crystal lattice (dashed bonds indicate hydrogen- and weak-bonding

Fig. 3. Molecular diagram as shown with 50% thermal ellipsoids and hydrogen atoms as spheres of arbitrary size. Perchlorate anions and lattice solvent have been omitted forclarity. The ligand substituent connected via N5 is modeled as disordered over two positions (approximately related by a 180� rotation about the long axis of the group) witheach component fixed at 50% occupancy. Only one disordered component is shown.

Fig. 4. Unit cell contents of C2 as viewed down the ‘a’ axis direction.

Table 4Selected bond distances (Å) and angles (�) and hydrogen bonds for C2.

Cu(1)–O(1) 1.968(4) N(4)–Cu(1)–N(2) 84.49(16)Cu(1)–N(4) 1.971(4) O(1)–Cu(1)–N(1) 83.69(15)Cu(1)–N(2) 2.000(4) N(4)–Cu(1)–N(1) 155.25(14)Cu(1)–N(1) 2.031(4) N(2)–Cu(1)–N(1) 86.93(16)Cu(1)–N(3) 2.193(4) O(1)–Cu(1)–N(3) 106.19(16)

N(4)–Cu(1)–N(3) 117.80(15)O(1)–Cu(1)–N(4) 99.67(16) N(2)–Cu(1)–N(3) 83.47(15)O(1)–Cu(1)–N(2) 165.70(14) N(1)–Cu(1)–N(3) 84.08(15)

136 J. Barreto et al. / Polyhedron 52 (2013) 128–138

As depicted in Fig. 5, the Cu(II) ion is facially coordinated to thethree nitrogen atoms of the tacn ring (N1–N3) with an average

bond length of 2.122 Å and two nitrogen atoms (N4 and N5) ofthe picolyl pendant arms (2.003(6) and 2.015(6), respectively).The Cu–Npyridyl bond distances are shorter than the Cu–Ntacn

distance (Table 5) and are within the range reported for otherpyridyl-containing copper(II) complexes [1,29,30]. This indicatesa stronger coordination of the macrocyclic ligand L4 to the Cu(II)centre. The calculated value of s is 0.28 for C3 indicates a SPstructure with some degree of distortion towards TBP. This isfurther supported by the fact that both trans-N–Cu–N angles,N(4)–Cu(1)–N(2) = 161.2(2)� and in particular N(5)–Cu(1)–N(3) = 144.8(2)�, are less than the expected 180� (Table 5).

Intermolecular hydrogen bond interactions were observed onlybetween the nitrogen atom N6 of the benzothiazole pendant arm

Fig. 5. Structure of the complex–cation C4 with atom-numbering scheme. Thermal ellipsoids are drawn at 30% probability level. Hydrogen atoms, perchlorate anions andsolvent molecules are omitted for clarity.

Table 5Selected bond distances (Å) and angles (�) for C4.

Cu(1)–N(1) 2.154(6) N(2)–Cu(1)–N(1) 85.0(2)Cu(1)–N(2) 2.027(6) N(4)–Cu(1)–N(1) 80.3(2)Cu(1)–N(3) 2.186(6) N(4)–Cu(1)–N(2) 161.2(2)Cu(1)–N(4) 2.003(6) N(4)–Cu(1)–N(3) 106.6(2)Cu(1)–N(5) 2.015(6) N(4)–Cu(1)–N(5) 97.5(2)

N(5)–Cu(1)–N(1) 129.6(2)N(1)–Cu(1)–N(3) 80.5(2) N(5)–Cu(1)–N(2) 83.0(3)N(2)–Cu(1)–N(3) 82.2(2) N(5)–Cu(1)–N(3) 144.8(2)

J. Barreto et al. / Polyhedron 52 (2013) 128–138 137

and the oxygen atom O8 of a perchlorate anion (N(6)–H(6). . .O(8),2.903(8) Å, \(DHA) = 161.7. The lattice is stabilized by intermolec-ular aromatic p–p stacking interaction between the pyridine ringsof the benzothiazole moiety with the inter-planar separation of3.698 Å (centre-to centre, Fig. 6).

3.2.4. Comparison of structuresAnalysis of the three structures, simplified view presented in

Fig. 7, reveals that the introduction of pyridyl groups into the tacnring modifies the coordination properties of the carbonyl groupconnecting the benzothiazole moiety to the macrocycle. Further-more, the copper(II) center prefers the pyridyl group over the car-bonyl group for metal coordination. Thus, introduction of thesegroups in the azamacrocyclic ring can limit the ability of the benzo-thiazole moiety to coordinate to the metal center. The geometry ofthe coordination complex formed with copper(II) varies accordingto the number and type of pendant arms. As discussed above, onependant arm on the tacn macrocycle presents a pseudo-octahedralgeometry around copper centre whereas the introduction of an

Fig. 6. Intermolecular p–p-interaction between two C4 molecules.

Fig. 7. Representation of the copper(II) cationic units of complexes C1, C2 and C4.

additional pyridyl pendant alters the geometry to distorted squarepyramidal with the degree of distortion being further enhanced to-wards trigonal bipyramidal upon introduction of a second pyridylgroup on the macrocycle. This is expected due to the steric hin-drance generated by the benzothiazole pendant arm and the mac-rocyclic constraints. In copper(II)-tacn complexes containingsmaller pendant arms like acetate together with two pyridyl armsit has been concluded that steric hindrance produced by these pen-dant arm can cause the change of geometry from distorted octahe-dral to distorted square pyramidal [1]. Han et al. have shown that inthe copper(II)-1,4,7-tris(2-pyridylmethyl)-1,4,7-triazacyclononanecomplex the copper center coordinates six nitrogen, three fromthe tacn ring and three from the pyridyl groups, presenting adistorted octahedron [31]. In the case of tris-o-aminobenzylsubstituted tacn (1,4,7-tris(o-aminobenzyl)-1,4,7-triazacyclo-nonane) the copper(II) center adopts a square pyramidal geometry

138 J. Barreto et al. / Polyhedron 52 (2013) 128–138

similar to that found in this study [32]. A related trisubstituted tacnligand consisting of two benzimidazole pendant arms and anadditional benzimidazole-2-yl-methyl group, which is linked tothe deprotonated nitrogen atom of benzimidazole-2-yl-methyl, asthe third arm (1-R-4,7-bis(benzimidazole-2-yl-methyl)-1,4,7-tri-azacyclononane, [R = 1-(benzimidazole-2-yl-methyl)benzimid-azole-2-yl-methy]) was prepared by Li et al. [33]. In this case, thethree benzimidazole pendant arms coordinated to the copper(II)forming an octahedral complex rather than distorted squarepyramidal as found for C3 in this study.

For the complex of the monosubstituted tacn derivative, C1, thecopper(II) center is in a pseudo-octahedral geometry with a strongJahn–Teller distortion caused by the acetonitrile molecule bondingweakly to the metal center, as is generally the case for six-coordi-nate copper(II) complexes. Berreau et al. [34] reported the synthe-sis of two copper(II)–tacn complexes in which the tacn macrocycleis substituted with one amide pendant arm (1,4-diisopropyl-7-(N-tertiary-butyl-N-methylacetamido)-1,4,7-triazacyclononane and1,4-diisopropyl-7-(N-tertiary-butyl-2-propionamido)-1,4,7-triaza-cyclononane) and found that the Cu(II) centers in both complexesadopted a distorted square pyramidal geometries in contrast to thepseudo-octahedral, as found for the mono-benzothiazole derivativeof tacn, C1. The flexibility of the pendant benzothiazole group in C1may have allowed the Cu(II) center to adopt a pseudo-octahedralgeometry.

4. Conclusions

Four benzothiazole derivatives of tacn have been synthesizedand used to prepare a series of copper(II) complexes. One impetusfor these studies is the potential application of these molecules asfuture amyloid binding agents for the detection of Alzheimer’s. It isclear from the present study that the introduction of picolyl unitsto the tacn ring changes the preferred geometry of the complexesfrom pseudo-octahedral towards square pyramidal, i.e., the metalcenter favors the formation of pentacoordinate complexes in thesolid state. In order to evaluate the potential of these complexes to-wards the detection of b-amyloid by PET and fluorescence imagingour ongoing investigations are focussing on studying their fluores-cent properties and their brain uptake.

Acknowledgements

This research was funded in part by the National Health andMedical Research Council through Program Grant 400121 (DCR)and the Australian Research Council. J.B and T.J. thank MonashGraduate Scholarship, Monash International Postgraduate Re-search Scholarship and Postgraduate Publication Award.

Appendix A. Supplementary material

CCDC # 881571, 881569 and 881570 contain supplementarycrystallographic data for C1, C2 and C4, respectively. These data

can be obtained free of charge via http://www.ccdc.cam.ac.uk/con-ts/retrieving.html, or from the Cambridge Crystallographic DataCentre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223336 033; or e-mail: deposit@ccdc.cam.ac.uk.

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