Synthesis, structure and anti-fungal activity of dimeric Ag(I) complexes containing bis-imidazole ligands

Synthesis, structure and anti-fungal activity of dimeric Ag(I) complexes containing bis-imidazole ligands Suaad Abuskhuna a , John Briody a , Malachy McCann a,* , Michael Devereux b , Kevin Kavanagh c , Julia Barreira Fontecha d , Vickie McKee d a Department of Chemistry, St. Patrick’s College, National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland b Dublin Institute of Technology, Cathal Brugha Street, Dublin, Ireland c Department of Biology, National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland d Department of Chemistry, Loughborough University, Loughborough, Leics LE11 3TU, UK Received 10 November 2003; accepted 4 February 2004 Abstract Five Ag(I) complexes containing the ligands bis(imidazol-2-yl)methane (2-BIM) and its derivatives were prepared and [Ag2(2BIM)2](ClO4)2and [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH were characterised using X-ray crystallography. In each dimer the two Ag(I) ions are two-coordinate and there are small but definite argentophilic Ag–Ag (d10–d10) interactions. All of the complexes display anti-fungal activity when tested in vitro against the fungal pathogen Candida albicans. Ó2004 Elsevier Ltd. All rights reserved. Keywords: Bis-imidazole; Bis(imidazol-2-yl)methane; X-ray structures; Silver(I); Argentophilicity; Anti-fungal; Candida albicans 1. Introduction In our efforts to develop new metal complexes that would greatly inhibit the growth of the human fungal pathogen Candida albicans [1–4] we have found that, to date, the most active drug tested in aqueous media is the Ag(I) complex [Ag(phendio)2]ClO4(phendio ¼1,10phenanthroline-5,6-dione) [5]. As part of these ongoing studies into the synthesis and in vitro testing of new metalbased anti-fungal drugs we report here the preparation of five Ag(I) complexes containing bis(imidazole) ligands. Bis(imidazol-2-yl)methane (2-BIM) and its derivatives (Fig. 1), in which the two imidazole rings are linked via a single tetrahedral carbon atom, can be viewed as primitive models for multi-histidine coordination in biological systems. Such bis(imidazole) ligands have been shown to form stable six-membered chelate rings with a variety of transition metals [6–12], and the Pt(II) complex [Pt(2BIM(Me)OH)Cl2] (2-BIM(Me)OH ¼bis(N-methylimidazol-2-yl)carbinol) [10] has been reported to exhibit notable antitumor activity. 2. Results and discussion In the current study, AgClO4was reacted at room temperature with methanolic solutions of the five bis(imidazole) ligands shown in Fig. 1 to give the respective Ag(I) complex in moderate to good yield. The complexes were soluble in hot acetonitrile and DMSO and insoluble in water. The X-ray crystal structure of [Ag2(2-BIM)2](ClO4)2(Fig. 2 and Table 1) showed the complex to be centrosymmetric, containing two Ag(2BIM)þunits. The two metal ions are two-coordinate and have identical atoms in the plane of the chelating ligand. Using its two imine N atoms each 2-BIM ligand bridges the pair of Ag(I) ions. All four N atoms (N1, N4A, N4, N1A) are coplanar and the two imidazole groups in each 2-BIM ligand have an interplanar angle of 75.52(8)°. The two Ag(I) ions are only weakly interacting, the distance separating them being 3.2612(4)  A. The binding of the two 2-BIM ligands is similar to that * Corresponding author. Tel.: +353-1-708-3767; fax: +353-1-7083815. E-mail address: [email protected] (M. McCann). 0277-5387/$ - see front matter Ó2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.poly.2004.02.006 Polyhedron 23 (2004) 1249–1255 www.elsevier.com/locate/poly observed for the Biim2ligand (Biim2¼2,20-biimidazolate) in the heteropolynuclear complex, [{Ru(pap)2 (Biim)}2Ag2](ClO4)2H2O (pap ¼2-(phenylazo)pyridine) [13]. The shorter Ag–Ag separation in the latter species is (2.8899  A) is mainly a consequence of the smaller size of the Biim2ligand compared to 2-BIM (no methylene bridge between the two imidazole rings in Biim2). The formula unit of [Ag2(2-BIM)2](ClO4)2is completed by two lattice perchlorate, which are involved in hydrogen bonding to the hydrogen atoms of the imidazole nitrogen atoms (N2 and N3, and N2A and N3A, respectively). The lattice perchlorate anions show unsymmetric bridging interactions with Ag(I) ions of neighbouring cations (AgOClO32.965(2) and 3.264(2)  A). There are hydrogen bonding interactions along the a and bdirections which link the units together in the lattice, forming sheets. However, there are no hydrogen bonds in the cdirection, that is to say, between the sheets. There are some intermolecular p–pinteractions involving the imidazole rings on adjacent dimer molecules and there is also evidence of some interdimer C–Hpinteractions between neighbouring imidazole functions. A perspective view of the cell packing is shown in Fig. 3. The X-ray crystal structure of [Ag2(2-BIM(Bz)- OH)2](ClO4)2EtOH (Fig. 4 and Table 2) shows the asymmetric unit containing one [Ag2(2-BIM(Bz)- OH)2]2þunit, two perchlorate anions and a solvate ethanol. The two Ag(I) ions are again bridged by the two ligands and each metal is approximately linearly coordinated to a pair of imine nitrogens. There are additional longer interactions with the perchlorate anions. The metal-metal distance of 3.018(4)  A is considerably shorter than in [Ag2(2-BIM)2](ClO4)2. Within the [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH complex molecule there appears to be some degree of intramolecular p–p interaction between the imidazole and phenyl rings of the opposing two 2-BIM(Bz)OH ligands in the dimer. Interestingly, the angles N(1A)–Ag(1)–Ag(2) and N(4B)–Ag(1)–Ag(2) are very different to one another (168.30(12)°and 68.35(8)°, respectively). One of the perchlorate anions in the complex is disordered and was modeled with two alternative sets of oxygen atom positions (50% occupancy each). The ethanol solvate is also disordered and was modeled as 50% occupancy of two alternative positions. Hydrogen atoms attached to carbon were inserted at calculated positions, whilst those attached to the 2-BIM(Bz)OH alcohol groups were located from difference maps and not further refined, those bonded to the disordered oxygen atom of the ethanol solvate were not located or included in the model. One view of the packing in the crystal is illustrated in Fig. 5. Repeated attempts to grow crystals of [Ag2{2-BIM (Me)}2](ClO4)2, [Ag2{2-BIM(CN)}2](ClO4)2and [Ag2{2BIM(BzCl)}2](ClO4)2suitable for X-ray structural analFig. 2. X-ray crystal structure of [Ag2(2-BIM)2](ClO4)2. RR' 2-BIM H H 2-BIM(Bz)OH PhCH2 OH 2-BIM(Me) Me H 2-BIM(CN) NC(CH2)2H 2-BIM(ClBz) Cl2PhCH2 H N N N N HR' R R Fig. 1. Ligand symbols and structures. Table 1 Selected bond lengths (  A) and angles (°) for [Ag2(2-BIM)2](ClO4)2 Bond lengths (  A) Ag(1)–N(4)#1 2.0953(17) Ag(1)–N(1) 2.0957(17) Ag(1)–Ag(1)#1 3.2612(4) Ag(1)–O(11)#2 2.965(2) Ag(1)–O(11)#3 3.264(2) Bond angles (°) N(4)#1–Ag(1)–N(1) 167.80(7) N(4)#1–Ag(1)–Ag(1)#1 91.08(5) N(1)–Ag(1)–Ag(1)#1 99.94(5) Symmetry transformations used to generate equivalent atoms: #1 xþ1;yþ1;zþ1; #2 1 þx;1þy;z;#31x;y;1z. 1250 S. Abuskhuna et al. / Polyhedron 23 (2004) 1249–1255 ysis were unsuccessful. However, given the close similarities in the core structures of all five bis(imidazole) ligands the latter three silver complexes are thought to be essentially isostructural with [Ag2(2-BIM)2] (ClO4)2and [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH and are thus also formulated as dimers. For [Ag2{2-BIM(CN)}2](ClO4)2 there is also the possibility of the pendant cyano groups participating in the bonding to the metal since Ag(I) has a high affinity for organonitrile donors. 2.1. In vitro anti-Candida studies All of the metal-free bis(imidazole) ligands and the Ag(I) complexes were screened for their ability to inhibit the growth of C. albicans. The minimum inhibitory concentration (MIC) is the concentration of drug (expressed as lg of complex per 1 cm3of aqueous growth medium solution) required to totally inhibit the growth of the fungal cells at 37 °C. As the complexes and the Fig. 4. X-ray crystal structure of [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH. Fig. 3. Packing diagram for [Ag2(2-BIM)2](ClO4)2. S. Abuskhuna et al. / Polyhedron 23 (2004) 1249–1255 1251 ligands were essentially water insoluble the tests were carried out as suspensions of the complexes in the aqueous growth medium. In addition, because the complexes were soluble in DMSO a series of anti-fungal tests were also conducted using DMSO/water solutions of the complexes (see Section 3). In all cases, the activity of the complexes were compared to that of a control system in which the cells were grown in the absence of any added complex or free ligand (under these conditions the fungal cell replication was rapid). In addition, under the present biological test conditions an aqueous suspension of the anti-Candida prescription drug ketoconazole had an MIC value of ca. 2.5 lgcm 3. All of the metal-free ligands were found to be inactive against the fungal cells. As aqueous suspensions, the silver complexes were moderately active with MIC value ranges indicated in brackets: [Ag2(2-BIM)2](ClO4)2(10– 20 lgcm 3); [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH (50– 100 lgcm 3); [Ag2{2-BIM(Me)}2](ClO4)2(20–50 lgcm 3); [Ag2{2-BIM(CN)}2](ClO4)2(20–50 lgcm 3). A considerable improvement in anti-fungal activity was observed upon administering the complexes as DMSO/ water solutions as opposed to aqueous suspensions: [Ag2(2-BIM)2](ClO4)2(5–10 lgcm 3); [Ag2(2-BIM(Bz)- OH)2](ClO4)2EtOH (2.5–5 lgcm 3); [Ag2{2-BIM (Me)}2](ClO4)2(2.5–5 lgcm 3); [Ag2{2-BIM(CN)}2] (ClO4)2(5–10 lgcm 3); [Ag2{2-BIM(BzCl)}2](ClO4)2 (5–10 lgcm 3). Besides greatly increasing the solubility of the complexes the DMSO is also thought to make the cells more permeable to the complexes so that they can enter the cells and exert their effects on the organism. In comparison, as an aqueous suspension [Ag(phendio)2]ClO4has an MIC value of 0.3 lgcm 3[5]. 3. Experimental Chemicals were purchased from commercial sources and, unless specified, were used without further purification. Literature methods were used to prepare 2-BIM [14,15], 2-BIM(Me) [7,16] and 2-BIM(OH)Bz [17]. The preparation of the silver complexes was conducted in the absence of light and the samples were stored in the dark. Infrared spectra of solids (in a KBr matrix) were recorded in the region 4000–400 cm1on a Nicolet FT-IR Impact 400D infrared spectrometer and 1H NMR spectra were run on a Bruker Avance 300 MHz instrument. Microanalytical data were provided by the Microanalytical Laboratory, National University of Ireland, Cork, Ireland. 3.1. 2-BIM(CN) Acrylonitrile (3.6 g, 67 mmol) was added to a mixture of 2-BIM (5.0 g, 34 mmol), and triethylamine (6.8 g, 67 mmol) in acetonitrile (150 cm3). The reaction mixture was refluxed with stirring for 5 h. The solvent was removed under reduced pressure giving a white solid, which was recrystallised from acetone. Yield: 4.7 g (55%). Mp 170 °C. Anal. Calc. C, 61.40; H, 5.50; N, Table 2 Selected bond lengths (  A) and angles (°) for [Ag2(2-BIM(Bz)OH)2] (ClO4)2EtOH Bond lengths (  A) Ag(1)–N(1A) 2.111(3) Ag(1)–N(4B) 2.134(3) Ag(1)–Ag(2) 3.0184(4) Ag(1)–O(11) 3.211(6) Ag(1)–O(13) 3.312(7) Ag(2)–N(1B) 2.119(3) Ag(2)–N(4A) 2.141(3) Ag(2)–O(21) 3.012(7) Ag(2)–O(210) 3.234(14) Bond angles (°) N(1A)–Ag(1)–N(4B) 168.30(12) N(1A)–Ag(1)–Ag(2) 103.65(8) N(4B)–Ag(1)–Ag(2) 68.35(8) N(1A)–Ag(1)–O(11) 82.69(13) N(4B)–Ag(1)–O(11) 105.55(13) Ag(2)–Ag(1)–O(11) 173.58(10) N(1A)–Ag(1)–O(13) 109.69(14) N(4B)–Ag(1)–O(13) 81.74(14) Ag(2)–Ag(1)–O(13) 133.53(10) O(11)–Ag(1)–O(13) 41.35(13) N(1B)–Ag(2)–N(4A) 172.79(12) N(1B)–Ag(2)–O(21) 92.53(19) N(4A)–Ag(2)–O(21) 93.9(2) N(1B)–Ag(2)–Ag(1) 99.97(8) N(4A)–Ag(2)–Ag(1) 74.23(8) O(21)–Ag(2)–Ag(1) 164.88(17) N(1B)–Ag(2)–O(210) 76.8(2) N(4A)–Ag(2)–O(210) 109.3(2) Ag(1)–Ag(2)–O(210) 174.4(2) Fig. 5. Packing diagram for [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH. 1252 S. Abuskhuna et al. / Polyhedron 23 (2004) 1249–1255 33.07. Found: C, 61.26; H, 5.47; N, 32.76%. 1H NMR(DMSO-d6): 7.17 (2H, d, J¼1:3 Hz), 6.8 (2H, d, J¼1:3 Hz), 4.3 (4H, t, J¼6:7 Hz), 4.2 (2H, s), 3.0 (4H, t, J¼6:7 Hz) ppm. 13C NMR(DMSO-d6): 143.6, 127.3, 120.8, 118.8, 25.4, 19.2 ppm. IR: 3125, 2932, 2264, 1485, 1447, 1383, 1287, 1166, 1134, 1089, 926, 722, 743, 705 cm1. Mass spec.: m=z: 254 (Mþ, 4%), 200 (4), 173 (8), 161 (6), 148 (10), 134 (11), 120 (14), 107 (14), 94 (28), 82 (84), 66 (20), 54 (100). 3.2. 2-BIM(BzCl) 2,6-Dichlorobenzyl chloride (0.53 g, 2.7 mmol) was added to a stirred mixture of 2-BIM (0.2 g, 1.3 mmol) and sodium hydride (0.06 g, 2.5 mmol) in dry DMF (15 cm3). The mixture was stirred overnight at room temperature and the solvent removed under reduced pressure. Water (20 cm3) was added and the product extracted with dichloromethane, and the dichloromethane solution was then dried over magnesium sulphate. After filtration the solvent was removed under reduced pressure. The resulting brown oily residue was digested in cyclohexane and the white product precipitated upon cooling. Yield: 0.34 g (54%). Mp 93 °C. Anal. Calc. C, 54.10; H, 3.43; N, 12.02. Found: C, 54.09; H, 3.58; N, 11.73%. 1H NMR (CDCl3): 7.4 (2H, d, J¼2 Hz), 7.1 (2H, dd, J¼8:3 Hz), 6.9 (2H, d, J¼1:3 Hz), 6.7 (2H, d, J¼1:3 Hz), 6.5 (2H, d, J¼8:3 Hz), 5.2 (4H, s), 4.2 (2H, s). 13C NMR (CDCl3): 143, 134.5, 133.6, 132.7, 129.5, 129.1, 128.1, 127.5, 120.5, 47, 27 ppm. IR: 2945, 1593, 1485, 1447, 1389, 1274, 1121, 1057, 849, 733, 682 cm1. Mass spec.: m=z: 466 (Mþ, 16%), 429 (4), 305 (26), 269 (8), 205 (8), 159 (100), 147 (8), 123 (16), 99 (6), 89 (16), 81 (38), 63 (10). 3.3. [Ag2(2-BIM)2](ClO4)2 Silver perchlorate (0.70 g, 3.37 mmol) was added to a stirred solution of 2-BIM (0.5 g, 3.37 mmol) in methanol (15 cm3) and the mixture stirred for 1 h at room temperature. The precipitated white was filtered off, washed with methanol and air-dried. Yield: 1.00 g (83%). Anal. Calc. C, 23.64; H, 2.25; N, 15.76. Found: C, 23.58; H, 2.13; N, 15.78%. IR: 3344, 3151, 1293, 1095, 759, 624 cm1.1H NMR (ppm DMSO): 6.8 (8H, s), 4 (4H, s). The complex was soluble in hot acetonitrile and DMSO, and crystals suitable for X-ray analysis were obtained by recrystallising from acetonitrile. 3.4. [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH This white complex was prepared and recrystallised in a similar way to [Ag2(2-BIM)2](ClO4)2using silver perchlorate (0.06 g, 0.17 mmol) and 2-BIM(Bz)OH (0.1 g, 0.29 mmol). Yield: 0.11 g (68%). Anal. Calc. C, 43.87; H, 3.48; N, 9.70. Found: C, 44.21; H, 3.45; N, 9.69%. IR: 2485, 3138, 2971, 1497, 1459, 1287, 1102, 827, 717, 624 cm1.1H NMR (ppm DMSO): 5.2 (8H, dd), 6.4 (2H, d), 7.1 (8H, s), 7.35 (20H, m). The complex was soluble in hot acetonitrile, hot acetone and DMSO. 3.5. [Ag2 { 2-BIM(Me) } 2](ClO4)2 To a solution of silver perchlorate (0.10 g, 0.48 mmol) in methanol (3 cm3) was added a solution of 2-BIM(Me) (0.10 g, 0.56 mmol) in methanol (3 cm3). A white precipitate formed immediately and the reaction mixture was stirred for 20 min at room temperature. The white product was filtered off, washed with methanol and then dried in air. Yield: 0.13 g (62%). Anal. Calc. C, 28.10; H, 3.13; N, 14.60. Found: C, 27.5; H, 3.00; N, 14.13%. IR: 3485, 3138, 2971, 1497, 1414, 1293, 1102, 772, 627 cm1. 1H NMR (ppm DMSO): 3.5 (12H, s), 4.36 (4H, s), 6.8 (4H, s), 7.2 (4H, s). The complex was soluble in hot acetonitrile, hot acetone and DMSO. 3.6. [Ag2 { 2-BIM(CN) } 2](ClO4)2 This white complex was prepared in a similar way to [Ag2{2-BIM(Me)}2](ClO4)2using silver perchlorate (0.10 g, 0.48 mmol) and 2-BIM(CN) (0.20 g, 0.78 mmol). Yield: 0.32 g (89%). Anal. Calc. C, 33.81; H, 3.03; N, 18.20. Found: C, 33.46; H, 2.92; N, 18.20%. IR: 3511, 3138, 2984, 2264, 1497, 1427, 1287, 1102, 756, 627 cm1. 1H NMR (ppm DMSO): 7.3 (4H, s), 6.8 (4H, s), 4.4 (4H, s), 4.2 (8H, t), 2.9 (8H, t). The complex was soluble in hot acetonitrile, hot acetone and DMSO. 3.7. [Ag2 { 2-BIM(BzCl) } 2](ClO4)2 This white complex was prepared in a similar way to [Ag2{2-BIM(Me)}2](ClO4)2using silver perchlorate (0.08 g, 0.38 mmol) in 3 ml methanol was added to 2BIM(BzCl) (0.20 g, 0.43 mmol). Yield: 0.16 g (57%). Anal. Calc. C, 37.43; H, 2.37; N, 8.31. Found: C, 37.03; H, 2.41; N, 8.04%. IR: 3511, 3138, 1593, 1491, 1395, 1274, 1102, 836, 749, 628 cm1.1H NMR (ppm DMSO): 7.9 (4H, d), 7.56 (4H, dd), 7.5 (4H, d),7.25 (4H, d) 6.8 (4H, d), 5.5 (8H, s), 4.8 (4H, s). The complex was soluble in hot acetonitrile, hot acetone and DMSO. 3.8. Anti-Candida testing Candida albicans ATCC 10231 was obtained from the American Type Culture Collection (Manasas, VA, USA). Cultures were grown on Sabouraud dextrose agar (SDA) plates at 37 °C and maintained at 4 °C for short-term storage. Minimum inhibitory concentrations (MICs) were determined as follows. RPMI-1640 broth medium was used for the anti-Candida susceptibility testing. RPMI (5.15 g) was dissolved in cold distilled water (425 cm3) in a 1-l Duran bottle and the pH S. Abuskhuna et al. / Polyhedron 23 (2004) 1249–1255 1253 adjusted to 4.0 using a few drops of HCl (ca. 2 M). The resulting solution was autoclaved and then allowed to cool to approximately 50 °C. Morpholinepropanesulfonic acid (MOPS) (17.3 g) and LL -glutamate (0.15 g) were dissolved together with stirring in distilled water (50 cm3) and the resulting solution filter sterilized. The MOPS and LL -glutamate solution was added to the warm RPMI and the pH of the mixture adjusted to 7.0 using sterile NaOH (6 M). Prior to MIC testing, cells were grown on SDA at 37 °C for 24 h. Cell suspensions were prepared in sterile phosphate buffered saline (PBS, pH 7.2) and cells were counted microscopically following dilution with PBS. A microtitre plate was inoculated with cells at a density of 5 105cells cm3. Test suspensions (in water) and solutions (in aqueous DMSO) of the silver complexes were each prepared as follows. Suspensions in water: the complex (0.02 g) was suspended in distilled water (10 cm3) to yield a stock suspension of concentration 2000 lgcm 3. Doubling dilutions of the stock suspension were made to yield a series of test suspensions ranging in complex concentration from 20 to 1.25 lgcm 3.Solutions in DMSO: the complex (0.02 g) was dissolved in DMSO (10 cm3)to yield a stock solution of concentration 2000 lgcm 3. Doubling dilutions of the stock solution were made using distilled water to yield a series of test solutions ranging in complex concentration from 20 to 1.25 lgcm 3. The DMSO concentration (% v/v) in the test solutions ranged from 1.0% to 0.06% (note that a 2% DMSO aqueous solution, without added complex, does not inhibit the growth of the microorganism whereas a 3% DMSO aqueous solution will arrest cell growth totally). For the aqueous test suspensions and the aqueous-DMSO test solutions the complex/cell mixtures were incubated at 37 °C for 24 h with continuous shaking and the assays were performed in triplicate. Plates were read using a Labsystems iEMS Reader MF (absorbance at k¼540 nm) and data were statistically analysed. 3.9. X-ray crystallography All of the data were collected at 150 K on a Bruker SMART 1000 diffractometer using Mo Karadiation (k¼0:71073  A). The structures were solved by direct methods and refined by full-matrix least-squares on F2 using all the reflections. One of the prechlorate anions in [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH is disordered and was modeled with two alternative sets of oxygen atom positions (50% occupancy each). The ethanol solvate is also disordered and was modeled as 50% occupancy of two alternative positions. All non-hydrogen atoms were refined with anisotropic atomic displacement parameters and hydrogen atoms bonded to carbon were inserted at calculated positions. Hydrogen atoms bonded to nitrogen ([Ag2(2-BIM)2](ClO4)2) or the ligand alcohol group ([Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH) were located from difference maps and not further refined; those bonded to the disordered oxygen of the ethanol solvate in [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH were not included in the model. All programmes used in the structure solution and refinement are included in the SHELXTLSHELXTL package [18] and data collection and refinement details are summarised in Table 3. Table 3 X-ray crystallographic data. Crystal data and structure refinement for [Ag2(2-BIM)2](ClO4)2and [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH Identification code [Ag2(2-BIM)2](ClO4)2[Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH Empirical formula C14H16Ag2Cl2N8O8C44H46Ag2Cl2N8O11 Formula weight 710.99 1149.53 Crystal system triclinic triclinic Space group P  1P  1 a(  A) 7.8149(10) 10.9636(7) b(  A) 8.9902(11) 14.7743(9) c(  A) 9.2559(11) 16.0180(10) a(°) 108.046(2) 114.3870(10) b(°) 98.283(2) 98.2900(10) c(°) 114.763(2) 95.8410(10) Volume (  A3) 532.47(11) 2300.6(2) Z12 F(0 0 0) 348 1164 Crystal size (mm) 0.16 0.25 0.31 0.37 0.25 0.14 hrange for data collection (°) 2.44–28.65 1.54–25.00 Reflections collected 4544 16522 Independent reflections [RðintÞ] 2396 [0.0186] 8050 [0.0159] Absorption correction multiscan multiscan Maximum and minimum transmission 1.0000 and 0.8116 1.000000 and 0.912980 Data/restraints/parameters 2396/0/154 8050/98/667 R1,wR2[I>2rðIÞ] 0.0198, 0.0526 0.0356, 0.0877 R1,wR2(all data) 0.0204, 0.0530 0.0455, 0.0942 1254 S. Abuskhuna et al. / Polyhedron 23 (2004) 1249–1255 4. Supplementary data X-ray supplementary data for [Ag2(2-BIM)2](ClO4)2 and [Ag2(2-BIM(Bz)OH)2](ClO4)2EtOH are available from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, England (fax: +441223-336033; E-mail: [email protected] or www: http://www.ccdc.cam.ac.uk), on request quoting the deposition numbers CCDC 219908 and CCDC 219909, respectively. Acknowledgements S. Abuskhuna acknowledges financial support from the Libyan Higher Education Department. References [1] B. Coyle, K. Kavanagh, M. McCann, M. Devereux, M. Geraghty, BioMetals 16 (2003) 321. [2] B. Coyle, P. Kinsella, M. McCann, M. Devereux, R. O’Connor, M. Clynes, K. Kavanagh, Toxicology in Vitro 18 (2004) 63. [3] M. Geraghty, J.F. Cronin, M. Devereux, M. McCann, BioMetals 13 (2000) 1. [4] M. McCann, B. Coyle, J. Briody, F. Bass, N. O’Gorman, M. Devereux, K. Kavanagh, V. McKee, Polyhedron 22 (2003) 1595. [5] M. McCann, B. Coyle, S. McKay, P. 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