Elena Barreiro

A novel hexanuclear silver(I) cluster containing a regular Ag6 ring with short Ag–Ag distances and an argentophilic interaction

The hexanuclear complex [HQ][Ag(p-mpspa)] (H2-p-mpspa = 3-(4-methoxyphenyl)-2-sulfanylpropenoic acid) was prepared by reacting the precursor [Ag(H-p-mpspa)] with diisopropylamine (Q). The complex was characterized by spectroscopic techniques and the structure was solved by a single crystal X-ray diffraction study. The crystal contains hydrogen-bonded diisopropylammonium cations and [Ag6(p-mpspa)6](6-) anions that are based on a regular Ag6 ring with each S-donor atom of the sulfanylcarboxylate ligand bridging two Ag atoms. The Ag-Ag bond distances, 2.8036(6) Å, are very short and suggest a closed shell d(10)···d(10) argentophilic interaction. To analyze the relative role of this interaction and that of the S-bridging atom the anionic [Ag6(p-mpspa)6](6-) moiety has been studied theoretically at the Hartree-Fock (HF) and 2(nd) order Møller-Plesset perturbation theory (MP2) levels on a very simple [Ag6(SH)6] A model system. A large model system [Ag6(p-mpspa)6](6-)B has also been studied by applying the ONIOM (QM/MM) approach using HF/UFF and MP2/UFF combinations as levels of theory. The six experimentally observed Ag(I)···Ag(I) supported interactions are reproduced when dispersion-type interactions are considered in the theory levels MP2 and ONIOM MP2/UFF for models A and B, respectively. The use of HF and ONIOM HF/UFF levels led to a similar hexanuclear structure but displayed a large hexagonal disposition without argentophilic contacts for both models A and B. The steric hindrance exerted by the ligands did not preclude the formation of argentophilic interactions, as observed experimentally.

New structural features in triphenylphosphinesilver(I) sulfanylcarboxylates

We investigated the reactions of 1.5 : 1 : 1 mole ratio mixtures of triphenylphosphine, silver nitrate and 3-(aryl)-2-sulfanylpropenoic acids H(2)xspa in chloroform/water, where in the acid nomenclature, spa = 2-sulfanylpropenoato and x = p, Clp, mp, diBr-o-hp or f with p = 3-phenyl-, Clp = 3-(2-chlorophenyl)-, mp = 3-methoxyphenyl-, diBr-o-hp = 3-(3,5-dibromo-2-hydroxyphenyl)- and f = 3-(2-furyl)-. The compounds [Ag(PPh(3))(Hpspa)](1), [(AgPPh3)2(xspa)][x = Clp (2), o-mp (3), p-mp (4), diBr-o-hp (5) and f (6)] and [Ag(PPh3)3(Hfspa)](7) were isolated and all except 7 were characterized by IR, Raman and FAB mass spectrometry and by 1H, 13C and 31P NMR spectroscopy. Compound 6 was also characterized by (13)C CP/MAS, and compounds 1 and 6 by (109)Ag NMR spectroscopy. The crystal structures of 1, 2, 3, 4.(CH3)2CO, 5, 6.(CH3)2CO and 7 were determined by X-ray diffraction. has a supramolecular structure based on hydrogen bonding between dinuclear units, and all the other complexes adopt discrete structures. 2, 3, 4.(CH3)2CO, 5, and 6.(CH3)2CO are tetranuclear, and 7 mononuclear. The tetranuclear complexes contain the eight-membered coordination ring Ag4S2O2 (2, 3, 4.(CH3)2CO, 6.(CH3)2CO) or the twelve-membered ring Ag4(CO2)2S2 (5).

Synthesis and antimicrobial activities of silver(I) sulfanylcarboxylates. Structural isomers with identically or unequally coordinated Ag centers in an Ag4S4 ring.

We have investigated the reactions of silver nitrate and 3-(aryl)-2-sulfanylpropenoic acids [H(2)xspa, x: p = 3-phenyl-, f = 3-(2-furyl)-, t = 3-(2-thienyl)-, py = 3-(2-pyridyl)-] and 2-cyclopentylidene-2-sulfanylacetic acid (H(2)L) in 1 : 1 and 2 : 1 molar ratios. The 1 : 1 molar ratio gave compounds of type [Ag(HL)]; reaction of these compounds with diisopropylamine and NaOH gave [HQ][Ag(L)] (HQ = diisopropylammonium) and Na[Ag(L)] x H(2)O, respectively. These compounds, as well as those of type [Ag(2)(L)] obtained with the 1 : 2 molar ratio, were isolated and characterized by IR and NMR ((1)H and (13)C) spectroscopy. (109)Ag NMR spectroscopy and ESI-MS spectrometry were also used in some cases. The crystal structures of [HQ][Ag(pspa)] (11), in which the presence of structural isomers was detected, and [HQ][Ag(cpa)] (15) were determined by X-ray diffractometry. The antimicrobial activity of the complexes against E. coli, S. aureus, B. subtilis, P. aeruginosa/Resistant P. aeruginosa, and C. albicans was tested.

Synthesis and antimicrobial activities of silver(I) 3-(substituted phenyl)sulfanylpropenoates.

We investigated the reactions of silver nitrate with 3-(substituted phenyl)-2-sulfanylpropenoic acids H(2)L [L=xspa, where spa=2-sulfanylpropenoato and xin{Clp=3-(2-chlorophenyl)-, -o-mp=3-(2-methoxyphenyl)-, -o-hp=3-(2-hydroxyphenyl)-, -p-hp=3-(4-hydroxyphenyl)-, diBr-o-hp=3-(3,5-dibromo-2-hydroxyphenyl)-}] in 1:1 and 2:1 molar ratios. The 1:1 reactions gave compounds of type [Ag(HL)], which reacted with NaOH to afford Na[Ag(L)].xH(2)O (x=1 or 2) and with diisopropylamine to afford [HQ][Ag(L)] (HQ=diisopropylammonium). The 2:1 reactions gave products of type [Ag(2)(L)]. All the new compounds were isolated and characterized by IR spectroscopy, and all except the 2:1 adducts (which were insoluble) were studied by (1)H and (13)C NMR spectroscopy; ESI-MS spectrometry was also used for [HQ][Ag(L)] and Na[Ag(L)].xH(2)O, and the crystal structures of H(2)Clpspa and [HQ][Ag(Clpspa)] were determined by X-ray diffractometry. The antimicrobial activities of the complexes against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Pseudomonas aeruginosa and carbapenem-resistant P. aeruginosa were evaluated and compared with those of Ag(I) complexes with other aryl sulfanylpropenoates or related ligands.

Au–O Interactions and others in triphenylphosphinegold(I) sulfanylpropenoates with diverse structures

We investigated the reactions of triphenylphosphinegold(I) chloride in ethanol or methanol with the 3-(2-aryl)-2-sulfanylpropenoic acids H2xspa [x = f, t, p; f = 3-(2-furyl)-, t = 3-(2-thienyl)-, p = 3-phenyl-; spa = 2-sulfanylpropenoato] in 1 ∶ 1 and 2 ∶ 1 mole ratios, and the reactions of diisopropylamine with the 1 ∶ 1 complexes. Compounds of types [Au(PPh3)(Hxspa)], [HQ][Au(PPh3)(xspa)] n(HQ = diisopropylammonium) and [(AuPPh3)2(xspa)] were isolated and characterized by IR, Raman and FAB mass spectrometry and by 1H, 13C and 31P NMR spectroscopy. The structures of (Htspa)2·Me2CO and of the complexes [Au(PPh3)(Hfspa)] n(1), [HQ][Au(PPh3)(pspa)] n(6), [(AuPPh3)2(fspa)] n(7), [(AuPPh3)2(tspa)]·2MeOH (8·2MeOH) and [(AuPPh3)2pspa]·2MeOH (9·2MeOH) were determined by X-ray diffractometry; those of the Au complexes exhibit π-stacking, hydrogen bonding and Au–Au and Au–O interactions as well as the expected Au–S and Au–P bonds.

Dinuclear triphenylphosphinegold(I) sulfanylcarboxylates: Synthesis, structure and cytotoxic activity against cancer cell lines.

Compounds of the type [(AuPPh(3))(2)(xspa)]; H(2)xspa [x:p=3-phenyl-, f=3-(2-furyl)-, t=3-(2-thienyl)-, -o-py=3-(2-pyridyl)-, Clp=3-(2-chlorophenyl)-, -o-mp=3-(2-methoxyphenyl)-, -p-mp=3-(4-methoxyphenyl)-, -o-hp=3-(2-hydroxyphenyl)-, -p-hp=3-(4-hydroxyphenyl)-, -diBr-o-hp=3-(3,5-dibromo-2-hydroxyphenyl)-; spa=2-sulfanyl propenoato] were synthesized and characterized by IR and NMR ((1)H, (13)C and (31)P) spectroscopy and by FAB mass spectrometry. The structures of [(AuPPh(3))(2)(Clpspa)], [(AuPPh(3))(2)(o-hpspa)], [(AuPPh(3))(2)(p-hpspa)].MeOH and [(AuPPh(3))(2)(diBr-o-hpspa)].2Me(2)CO show the dinuclear nature of the complexes with the two gold atoms, one of which is also O-bonded to an O atom of the carboxylate group, bonded to the S atom. The in vitro antitumor activities against the HeLa-229, A2780 and A2780cis cell lines were determined and the compounds were found to be highly effective, in particular against the A2780cis cell line, with eight of the nine compounds having IC(50) values better than that of cisplatin. This behavior is indicative of a high ability to circumvent the cellular resistance to this drug.

Synthesis, Structural Characterization, and Antiinflammatory Activity of Triethylphosphinegold(I) Sulfanylpropenoates of the Type [(AuPEt3)2xspa] [H2xspa = 3-(Aryl)-2-sulfanylpropenoic acid] : an (H2O)6 Cluster in the Lattice of the Complexes [(AuPEt3)2xspa] ·3H2O

Gold complexes of the type [(AuPEt3)2xspa] were prepared by reacting AuPEt3Cl in basic media with the 3-(aryl)-2-sulfanylpropenoic acids H2xspa [x = p, Clp, -o-mp, -p-mp, -o-hp, -p-hp, diBr-o-hp, f, t, -o-py; p = 3-phenyl, Clp = 3-(2-chlorophenyl)-, -o-mp = 3-(2-methoxyphenyl)-, -p-mp = 3-(4-methoxyphenyl)-, -o-hp = 3-(2-hydroxyphenyl)-, -p-hp = 3-(4-hydroxyphenyl)-, diBr-o-hp = 3-(3,5- dibromo-2-hydroxyphenyl)-, f = 3-(2-furyl)-, t = 3-(2-thienyl)-, -o-py = 3-(2-pyridyl); spa = 2-sulfanylpropenoato], and 2-cyclopentylidene-2-sulfanylacetic acid (H2cpa). The complexes were characterized by spectroscopic methods (IR, (1)H, (13)C and (31)P NMR) and mass spectrometry, and the complexes [(AuPEt3)2pspa] x 3 H2O, [(AuPEt3)2-p-hpspa] x 3 H2O, [(AuPEt3)2tspa)] x 3 H2O, and [(AuPEt3)2-o-hpspa] by X-ray diffractometry. The crystals of the first three complexes contain (H2O)6 clusters hydrogen bonded to [(AuPEt3)2xspa]2 dimer units, whereas in the -o-hpspa derivative the hydrogen bonds are between the monomer [(AuPEt3)2-o-hpspa] units. The antiinflammatory activity of the complexes against plantar edema induced by carrageenan in rats is generally significant, with the values for the o-hpspa and tspa derivatives being particularly high.

Heteronuclear gold(I)-silver(I) sulfanylcarboxylates: Synthesis, structure and cytotoxic activity against cancer cell lines.

Heteronuclear complexes of the type [AgAu(PPh3)2(xspa)] [H2xspa=3-(aryl)-2-sulfanylpropenoic acids; (x=3-phenyl-; 3-(2-chlorophenyl)-; 3-(o-methoxyphenyl)-; 3-(p-methoxyphenyl)-; 3-(p-hydroxyphenyl)-; 3-(2-furyl)-; 3-(2-thienyl)-; spa=2-sulfanylpropenoate)] were prepared by reacting the appropriate [Au(PPh3)(Hxspa)] precursor with Ag(PPh3)NO3. The compounds were characterized by spectroscopic methods, (IR; (1)H, (13)C and (31)P NMR) and mass spectrometry and the structures of the phenyl and p-methoxyphenyl derivatives were determined by X-ray diffraction. The in vitro antitumor activity against the HeLa-229, A2780 and A2780cis cell lines was determined and compared with that of cisplatin and the equivalent homonuclear gold(I) complexes.

Synthesis, structure and cytotoxicity studies of diisopropylammonium and triethylammonium salts of triphenylphosphinegold(I) sulfanylcarboxylates

Compounds of the type [HQ][Au(PPh(3))(xspa)] and [HP][Au(PPh(3))(xspa)] {HQ=diisopropylammonium; HP=triethylammonium; H(2)xspa=3-aryl-2-sulfanylpropenoic acids [x: p=3-phenyl-, f=3-(2-furyl)-, t=3-(2-thienyl)-, -o-py=3-(2-pyridyl)-, Clp=3-(2-chlorophenyl)-, -o-mp=3-(2-methoxyphenyl)-, -p-mp=3-(4-methoxyphenyl)-, -o-hp=3-(2-hydroxyphenyl)-, -p-hp=3-(4-hydroxyphenyl)-, diBr-o-hp=3-(3,5-dibromo-2-hydroxyphenyl]} were synthesized and characterized by IR and NMR ((1)H, (13)C and (31)P) spectroscopy and by FAB mass spectrometry. The structures of [HQ][Au(PPh(3))(Clpspa)] and [HQ][Au(PPh(3))(-o-mpspa)] show that the crystal contains hydrogen-bonded diisopropylammonium cations and [Au(PPh(3))(xspa)](-) anions. The anions in the two compounds have different structures, with the carboxylate group either coordinated or not coordinated to the gold atom, respectively. The in vitro antitumour activities against the HeLa-229, A2780 and A2780cis cell lines were determined for all complexes. The diisopropylammonium derivatives were generally found to be more active, in particular against the A2780cis cell line, and showed a high ability to circumvent the cellular resistance to cisplatin.

Mono and dinuclear phosphinegold(I) sulfanylcarboxylates: influence of nuclearity and substitution of PPh3 for PEt3 on cytotoxicity.

Gold complexes of the type [Au(PEt3)(Hxspa)] were prepared by reacting triethylphosphinegold(I) chloride in ethanol/water (8:1) with the 3-(aryl)-2-sulfanylpropenoic acids H2xspa [x=p=3-phenyl-; f=3-(2-furyl)-; t=3-(2-thienyl)-; py=3-(2-pyridyl); Clp=3-(2-Chlorophenyl)-; -o-mp=3-(2-methoxyphenyl)-; -p-mp=3-(4-methoxyphenyl)-; -o-hp=3-(2-hydroxyphenyl)-; -p-hp=3-(4-hydroxyphenyl)-; -diBr-o-hp=3-(3,5-dibromo-2-hidroxyphenyl-); spa=2-sulfanylpropenoato] or 2-cyclopentylidene-2-sulfanylacetic acid (H2cpa) and KOH in a 1:1:1 mole ratio. The compounds were characterized by IR spectroscopy and FAB mass spectrometry and by (1)H, (13)C and (31)P NMR spectroscopy. The in vitro antitumor activity of these and of the previously described dinuclear [(AuPEt3)2(xspa)] complexes against the HeLa-229, A2780 and A2780cis cell lines was determined and compared with those of the analogous PPh3 complexes. The results show that the substitution of the PPh3 ligand by PEt3 is particularly effective in increasing the cytotoxicity of the dinuclear [(AuPR3)2(xspa)] complexes, giving rise to compounds that are significantly more active than cisplatin against the aforementioned cell lines. In addition, and as a preliminary test for nephrotoxicity, the cytotoxicity of the most active compounds against the normal renal LCC-PK1 cell line was evaluated and compared with that of cisplatin.