Mariano Laguna

Anticancer therapeutics that target selenoenzymes: synthesis, characterization, in vitro cytotoxicity, and thioredoxin reductase inhibition of a series of gold(I) complexes containing hydrophilic phosphine ligands.

Gold(I) complexes bearing water‐soluble phosphine ligands, including 1,3,5‐triaza‐7‐phosphaadamantane (PTA), 3,7‐diacetyl‐1,3,7‐triaza‐5‐phosphabicyclo[3.3.1]nonane (DAPTA), and sodium triphenylphosphine trisulfonate (TPPTS), in combination with thionate ligands, were screened for their antiproliferative activities against human ovarian cancer cell lines A2780 either sensitive or resistant to cisplatin. In addition, the compounds were screened for their inhibition of mammalian thioredoxin reductases (TrxR), enzymes that are overexpressed in many tumor cells and contribute to drug resistance. The gold(I)–phosphine complexes efficiently inhibited cytosolic and mitochondrial TrxRs at concentrations that did not affect the related oxidoreductase glutathione reductase (GR). Additional complementary information on the enzyme metallation process and potential gold binding sites was obtained through the application of a specific biochemical assay using a thiol‐tagging reagent, BIAM (biotin‐conjugated iodoacetamide).

Synthesis, Characterization, and in Vitro Cytotoxicity of Some Gold(I) and Trans Platinum(II) Thionate Complexes Containing Water-Soluble PTA and DAPTA Ligands. X-ray Crystal Structures of [Au(SC4H3N2)(PTA)], trans-[Pt(SC4H3N2)2(PTA)2], trans-[Pt(SC5H4N)2(PTA)2], and trans-[Pt(SC5H4N)2(DAPTA)2]

A series of gold(I) and platinum(II) complexes of the type [Au(SR)(P)] and trans-[Pt(SR) 2(P) 2] [SR = 2-thiopyridine (SPy), 2-thiopyrimidine (SPyrim); P = 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA)] were prepared and characterized, and their in vitro cytotoxicities against a panel of seven human cancer cell lines were evaluated. The highly water soluble gold(I) complexes [Au(SR)(P)] [P = PTA and SR = SPy ( 1), SPyrim ( 2); P = DAPTA and SR = SPy ( 3), SPyrim ( 4)] showed low cytotoxicity, while the platinum(II) complexes trans-[Pt(SR) 2(P) 2] [P = PTA and SR = SPyrim ( 5), SPy ( 6); P = DAPTA and SR = SPyrim ( 7), SPy ( 8)] demonstrated potent cytotoxicity for ovarian, colon, renal, and melanoma cancer cell lines on the basis of a comparison with ID 50 values for some established cytotoxic drugs. Single crystals of 2, 5, 6, and 8 suitable for X-ray structural characterization were obtained, and the study revealed the trans configuration for 5, 6, and 8 in their solid states.

Coordination chemistry of gold(II) complexes

Abstract The number of complexes with gold in a formal oxidation state of two have increased considerably and nowadays this oxidation state can be considered nearly as a common state in gold chemistry. This review covers the evolution of the knowledge of this oxidation state from the first dithiocarbamate derivatives [Au 2 (S 2 CNR 2 ) 2 X 2 ], stable only at very low temperature, to the room temperature stable dinuclear gold complexes [Au 2 (L–L) 2 X 2 ] (L–L=CH 2 PPh 2 CH 2 , CH 2 PPh 2 S, C 5 H 4 PPh 2 -2; X=halogen). Although a dinuclear structure with a gold(II)–gold(II) bond supported by two equal bridging ligands were the first and most common, this review shows the present diversity as mononuclear, [Au([9]aneS 3 ) 2 ](BF 4 ) 2 , dinuclear with two different bridging ligands, [Au 2 (S 2 CNR 2 )(CH 2 PPh 2 CH 2 )X 2 ], with a non-supported metal–metal bond, [Au 2 (Ph 2 PC 8 H 6 PPh 2 ) 2 Cl 2 ](PF 6 ) 2 , and polynuclear gold(II) complexes either with chains of only gold centers or with other metals, such as [{(C 6 F 3 H 2 )Au(CH 2 PPh 2 CH 2 ) 2 Au} 2 Au 2 (CH 2 PPh 2 CH 2 ) 2 ]ClO 4 or [Au 2 Pt(CH 2 PPh 2 S) 4 X 2 ]

Anionic perfluorophenyl complexes of gold(I) and gold(III)

Abstract The preparation of organogold(I) anions of the types [AuRX]−, [AuR2]− and [AuRR′]− (R,R′ = C6F5 or 2,4,6,-C6F3H2; X = Cl, i, SCN. CN or N3) is accomplished in which the tetrahydrothiophen group of AuR(tht) is substituted by X,R or R′. Oragnogold(III) complexes of the general formulae [Aur2X2]−, [AuRR′X2]−, [AuR3X]− and [AuR4]− (R, R′ = C6F5, 2,3,4,6-C6F4H or 2,4,6,-C6F3H2; X = Cl, Br or I) are obtained either by oxidation of the above-mentioned gold(I) complexes or by substitution reactions of AuCl3(tht). The assignment of the cis- or, respectively, trans-configuration of the [AuR2X2]− derivatives is based on their IR spectra.

Detection of volatile organic compound vapors by using a vapochromic material on a tapered optical fiber

A low-cost optical fiber sensor to detect volatile organic compounds has been developed. Changes of up to 13.5 dB in the transmitted optical power have been detected with different concentrations of acetone and dichloromethane vapors. The device uses a standard single-mode fiber. The sensing mechanism relies on a vapor-induced refractive index change in a film of a vapochromic material deposited on the thinner region of a tapered fiber.

Gold(I) and gold(III) complexes containing bis(diphenylphosphine)methane disulfide or bis(diphenylphosphine)amine disulfide ligands

Abstract The reaction of SPPh2CH2PPh2S with gold(I) or gold(III) complexes containing weakly coordinated ligands lead to the formation of the binuclear complexes RAuSPPh2CH2PPh2SAuR (R = C6F5), or [Au2{SPPh2CH2PPh2S}2](ClO4)2, the mononuclear complexes, R3AuSPPh2CH2PPh2S, or, [R2 AuSPPh 2 CH 2 PPh 2 S ]ClO4. The last complex reacts with NaH to give R2AuSPPh2CHPPh2S which reacts with gold(I) or silver(I) derivatives to give binuclear, R2 AuSPPh 2 C HPPh2SAuR, or trinuclear complexes, [{R2 AuSPPh 2 C HPPh2S}2M]ClO4 (M = Au or Ag). Reaction of SPPh2NHPPh2S with RAuTHT, ClAuTHT (THT = tetrahydrothiophen) or [R2AuCl]2 gives [AuSPPh2NPPh2S]2 or R2 AuSPPh 2 NPPh 2 )S , containing the deprotonated ligand.

Gold complexes with heterocyclic thiones as ligands. X-Ray structure determination of [Au(C5H5NS)2]ClO4

Displacement of the weakly co-ordinating tetrahydrothiophene (tht) ligand in [AuX(tht)], [Au(tht)2]ClO4, or [Au(PPh3)(tht)]ClO4(X = Cl or C6F5) by heterocyclic thiones HL (HL = C3H5NS2, C4H4N2S, C5H5NS, C7H5NS2, or C7H6N2S), leads to the formation of neutral or cationic complexes of the types [AuX(HL)], [Au(HL)2]ClO4, or [Au(PPh3)(HL)]ClO4. For gold(III) complexes the tht ligand cannot be displaced but [Au(C6F5)3(OEt2)] reacts with HL to give neutral complexes [AuR3(HL)]. Deprotonation of the NH unit in the cationic complexes leads to neutral monomeric complexes and since the deprotonated N atom is now a donor, binuclear complexes can be prepared by displacement of a weakly co-ordinating ligand from other suitable complexes. The structure of [Au(HL)2]ClO4(HL = C5H5NS) has been established by X-ray crystallography [space group P, a= 9.609(3), b= 15.024(6), c= 16.712(7)A, α= 97.52(4), β= 104.17(2), γ= 104.76(2)°, and R′= 0.045 for 5 499 unique observed reflections]. The cations are arranged in a way that is unprecedented for gold(I) compounds. Five of the six cations in the cell are linked by short Au ⋯ Au contacts (3.3 A) and the sixth cation is monomeric.

Synthesis and reactivity of bimetallic Au–Ag polyfluorophenyl complexes; crystal and molecular structures of [{AuAg(C6F5)2(SC4H8)}n] and [{AuAg(C6F5)2(C6H6)}n]

The reaction of [NBun4][AuR2](R = C6F5 or C6F3H2-2,4,6) with Ag[ClO4] leads to complexes [{AuAgR2}n], which react with neutral ligands to give complexes [{AuAgR2L}n](L = neutral O-, N-, S- or P-donor ligand, alkene, or alkyne). For R = C6F5 and L = diphenylacetylene, the product is [{AuAgR2·0.5L}n]; the 0.5L can be displaced by other ligands, such as acetone, arenes, or alkenes, to reform [{AuAgR2L}n]. An X-ray diffraction study of [{AuAgR2L}n](R = C6F5, L = tetrahydrothiophene) reveals (AuAg)2 rings with Au–Ag 2.726 and 2.718 A(the first reported Au–Ag bond lengths), linked by Au ⋯ Au short contacts (2.889 A) to form infinite metal-atom chains. This complex crystallizes in space group Pccn, with a= 11.185(3), b= 22.475(6), c= 14.802(4)A, Z= 8, R= 0.041 for 2 005 reflections. The complex [{AuAgR2L}n](R = C6F5, L = benzene) crystallizes in space group C2/c, with a= 24.231(5), b= 7.570(1), c= 22.613(5)A, β= 117.49(2)°, Z= 8, and R= 0.035 for 3 008 reflections; it shows the same type of metal-atom chain (Au ⋯ Au 3.013; Au–Ag 2.702 and 2.792 A). The benzene ring is co-ordinated by one edge to silver. In both structures the gold atoms lie on a crystallographic two-fold axis.

Thiolato gold(i) complexes containing water-soluble phosphane ligands

A series of thiolate gold(I) derivatives bearing water soluble phosphanes--namely sodium triphenylphosphane monosulfonate (TPPMS), sodium triphenylphosphane trisulfonate (TPPTS), 1,3,5-triaza-7-phosphaadamantane (PTA) and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA)--is reported and the compounds studied for their luminescence properties in the solid state. Two of these derivatives, [Au(SMe(2)pyrim)(PTA)] and [Au(SBenzoxazole)(DAPTA)], are also structurally characterized by X-ray diffraction analysis. Strong antiproliferative effects are observed for most of the compounds in the human ovarian carcinoma cell lines (A2780/S) and its cisplatin-resistant variant (A2780/R), which depend on both the type of thiolate and phosphane ligands. ICP-MS studies were also performed to evaluate the influence of the gold uptake on the cytotoxic potency of the compounds.

trans-Thionate Derivatives of Pt(II) and Pd(II) with Water-Soluble Phosphane PTA and DAPTA Ligands: Antiproliferative Activity against Human Ovarian Cancer Cell Lines

A series of PTA and DAPTA platinum(II) and palladium(II) thionate complexes of the type trans-[M(SN)2P2] were prepared from the reaction of cis-[MCl2P2] [M = Pt, Pd; P = PTA (1,3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)] with the in situ generated sodium salts of the heterocyclic thiones S-m-methylpyrimidine-2-thione, S-4,6-dimethylpyrimidine-2-thione, S-4,6-dihydroxypyrimidine-2-thione, benzothiazole-2-thione, benzoxazole-2-thione, S-1,3,4,-thiadiazole-2-thione, S-4,5-H-thiazolan-2-thione, and S-pyrimidine-4(1H)-one-2-thione. The X-ray structures of six of the compounds confirm the trans disposition and, only in the case of [Pd2Cl2(S-pyrimidine-4(1H)-one-2-thionate)2(PTA)2], a dinuclear structure with a Pd-Pd distance of 3.0265(14)Å was observed. In vitro cytotoxicities against human ovarian cancer cell lines A2780 and A2780cisR were evaluated for ten complexes showing a high inhibition of cellular growth with a comparable inhibitory potency (IC50) against A2780 cells to that of cisplatin. Notably, the compounds also show significant (up to 7-fold higher) activity in cisplatin-resistant A2780cisR cell lines.