M. Monim-ul-Mehboob

The synthesis, spectroscopic characterization and anticancer activity of new mono and binuclear phosphanegold(I) dithiocarbamate complexes

A new series of mononuclear [t-Bu3PAuS2CN(C7H7)2] (1), and binuclear [(DPPM)Au2(S2CN(CH3)2)2] (2), [(DPPM)Au2(S2CN(C2H5)2)2] (3) and [(DPPM)Au2(S2CN(C7H7)2)2] (4) [where DPPM = 1,1-bis(diphenylphosphino)methane, S2CN(CH3)2 = dimethyldithiocarbamate, S2CN(C2H5)2 = diethyldithiocarbamate and S2CN(C7H7)2 = dibenzyldithiocarbamate] gold(I) complexes have been prepared by reacting gold(I) precursors and dialkyl–diaryl dithiocarbamate ligands. The complexes were characterized by an analytical technique and spectroscopic methods such as CHNS analysis, FTIR spectroscopy; 1H, 13C and 31P NMR measurements. The molecular structure of the [t-Bu3PAuS2CN(C7H7)2] (1) complex was determined by X-ray diffraction. The gold(I) complexes (2 and 3) were found particularly to be better potent in vitro cytotoxic agents in comparison to cisplatin against HeLa, HCT15 and A549 cancer cell lines. These metal complexes could serve as attractive anticancer agents for the development of novel therapeutic strategies and to treat cervix, lung and colon cancers.

Synthesis, characterization and anti proliferative effect of [Au(en)2]Cl3 and [Au(N-propyl-en)2]Cl3 on human cancer cell lines

Two Au(III) complexes of the type [Au(en)2]Cl3 (2a) and [Au(N-pr-en)2]Cl3 (3a) were synthesized by reacting Auric acid (HAuCl(4)·3H2O) with 2 equiv. ethylenediamine (en) or N-alkyl substituted ethylenediamine ligands. This metallodrug was characterized by various analytical and spectroscopic techniques such as elemental analysis, UV-Vis, Far-IR, 1H NMR and solution 13C as well as solid 13C and 15N NMR. Potentiality of [Au(en)2]Cl3 and [Au(N-pr-en)2]Cl3 as an anti-cancer agent were investigated by measuring some relevant physicochemical and biochemical properties such as stability of Au-N bonds by vibrational stretching from Far IR as well as cytotoxicity and stomach cancer cell inhibiting effect, respectively. The solid-state 15N NMR chemical shift shows that the ligand is strongly bound to gold(III) centre via N atoms. The computational study of 2a shows that the gold coordination sphere adopts distorted square planar geometry with bidentate ethylenediamine ligands acting as a tetradentate chelate. While stable in the solution state, the in vitro biological studies performed with these compounds 2a in solution showed higher activity towards the inhibitory effects of the human cancer cell lines such as prostate cancer (PC-3) and gastric carcinoma (SGC-7901) than that of the N-substituted gold(III) complex (3a). Cytotoxicity of the new compounds has also been estimated in PC-3 and SGC-7901 cells.

New bipyridine gold(III) dithiocarbamate-containing complexes exerted a potent anticancer activity against cisplatin-resistant cancer cells independent of p53 status

We synthesized, characterized and tested in a panel of cancer cell lines, nine new bipyridine gold(III) dithiocarbamate-containing complexes. In vitro studies demonstrated that compounds 1, 2, 4, 5, 7 and 8 were the most cytotoxic in prostate, breast, ovarian cancer cell lines and in Hodgkin lymphoma cells with IC50 values lower than the reference drug cisplatin. The most active compound 1 was more active than cisplatin in ovarian (A2780cis and 2780CP-16) and breast cancer cisplatin-resistant cells. Compound 1 determined an alteration of the cellular redox homeostasis leading to increased ROS levels, a decrease in the mitochondrial membrane potential, cytochrome-c release from the mitochondria and activation of caspases 9 and 3. The ROS scavenger NAC suppressed ROS generation and rescued cells from damage. Compound 1 resulted more active in tumor cells than in normal human Mesenchymal stromal cells. Gold compounds were active independent of p53 status: exerted cytotoxic effects on a panel of non-small cell lung cancer cell lines with different p53 status and in the ovarian A2780 model where the p53 was knocked out. In conclusion, these promising results strongly indicate the need for further preclinical evaluation to test the clinical potential of these new gold(III) complexes.

Tetrakis(thione)platinum(II) complexes: synthesis, spectroscopic characterization, crystal structures, and in vitro cytotoxicity

A new series of platinum(II) complexes based on thione ligands with general formula [Pt(thione)4]X2 (X− = Cl−, NO3−) has been synthesized and characterized using CHNS elemental analysis, infrared, 1H and 13C solution-state NMR as well as 13C and 15N solid-state NMR spectroscopy, and X-ray crystallography. The spectroscopic methods confirm the coordination of Pt(II) with thiocarbonyl groups via sulfur of the thione ligands. The X-ray structures showed a distorted square planar geometry for 1, [Pt(MeImt)4]Cl2 (MeImt = N-Methylimidazolidine-2-thione) while the hydrogen bonding interactions in 7, [Pt(iPrImt)4](NO3)2·0.6(H2O) induce a bent see-saw distortion relative to the ideal square planar geometry. The in vitro cytotoxicity studies showed that 2, [Pt(EtImt)4]Cl2 is generally the most effective, a two-fold better cytotoxic agent than cisplatin and carboplatin against MCF7 (human breast cancer). Graphical abstract

Synthesis, spectroscopic characterization, X-ray structure and electrochemistry of new bis(1,2-diaminocyclohexane)gold(III) chloride compounds and their anticancer activities against PC3 and SGC7901 cancer cell lines

New gold(III) compounds with chemical formulae [Au{cis-(1,2-DACH)}2]Cl31, [Au{trans-(±)-(1,2-DACH)}2]Cl32 and [Au{(S,S)-(+)-1,2-(DACH)}2]Cl33 (where 1,2-DACH = 1,2-diaminocyclohexane) have been synthesized. The synthesized compounds were characterized using elemental analysis, various spectroscopic techniques including UV-vis, FTIR spectroscopy, solution and solid-state NMR measurements; and X-ray crystallography. The stability of compounds 1, 2 and 3 was checked by UV-vis spectroscopy and NMR measurements. The electrochemical behavior was also investigated through cyclic voltammetry. The potential of the three compounds as anticancer agents was investigated by measuring in vitro cytotoxicity in terms of IC50 and inhibitory effects on growth of human prostate (PC3) and gastric (SGC7901) cancer cell lines. [Au{trans-(±)-(1,2-DACH)}2]Cl3 (2) showed a better in vitro inhibitory effect on growth of human prostate (PC3) and gastric (SGC7901) cancer cell lines than [Au{cis-(1,2-DACH)}2]Cl3 (1) and [Au{(S,S)-(+)-(1,2-DACH)}2]Cl3 (3).

Some new [(thione)2Au(diamine)]Cl3 complexes: synthesis, spectroscopic characterization, computational and in vitro cytotoxic studies.

Recent advances in oncology are focused on developing new complexes of gold(III) with various ligands that show augmented anti-proliferative potential and reduced toxicity as compared to cis-platin. In this study, new Au(III) complexes of the type [(thione)2Au(diamine)]Cl3 are reported, where thione=1,3-imidazolidine-2-thione (Imt), 1,3-Diazinane-2-thione (Diaz) and diamine=1,2-diaminoethane (en), 1,3-diaminopropane (pn) or 1,4-diaminobutane (bn). The solid state IR as well as (13)C and (15)N NMR data indicate that Au(III) center is bonded via sulfur of thiocarbonyl SC site of the thiones and also chelated by the diamines from the trans side of coordinated thiones. Spectroscopic data are evaluated by comparisons with calculated data from the built and optimized structure by GAUSSIAN 09 at the RB3LYP level with LanL2DZ bases set. These new Au(III) complexes based on mixed thione and diamine ligands are very similar to the square planar structure of tetracoordinate [Au(en)2]Cl3complex. In this study, cytotoxicity data for these gold(III) complexes against C6 glioma cell lines are also reported, and the results indicate some complexes have cytotoxicity comparable to cis-platin.

Synthesis, CP-MAS NMR Characterization, and Antibacterial Activities of Glycine and Histidine Complexes of Cd(SeCN)2 and Hg(SeCN)2

The synthesis and characterization of cadmium and mercury complexes of selenocyanate of the type [(L)M(SeCN)2] are described, where L is L-Histidine (His) or L-Glycine (Gly) and M is Cd2+ or Hg2+. These complexes are obtained by the reaction of 1 equivalent of respective amino acids with metal diselenocyanate precursor in a mixture of solvents (methanol : water = 1 : 1). These synthesized compounds are characterized by analytical and various spectroscopic techniques such as elemental analysis (EA), IR, H,1 and C13 NMR in solution and in the solid state for C13 and N15. The in vitro antibacterial activities of these complexes have been investigated with standard type cultures of Escherichia coli (MTCC 443), Klebsiella pneumoniae (MTCC 109), Pseudomonas aeruginosa (MTCC 1688), Salmonella typhi (MTCC 733), and Staphylococcus aureus (MTCC 737).

Structural characterization and antimicrobial activity of a silver(I) complex of arginine

A silver(I) complex of arginine (arg), [Ag(arg)]NO3•0.5H2O (1) was prepared and characterized by elemental analysis, IR and NMR spectroscopy, and X-ray crystallography. The IR and NMR spectroscopic data confirmed the coordination of the ligand to silver(I). The structure of 1 shows that it is polymeric with each silver atom bound to the carboxyl O atom of one arginine ligand and to the amino N atom of another adopting a linear coordination environment. The two coordinate N–Ag–O units are repeated to form infinite chains. The molecular structure is stabilized by N–H…O and C–H…O hydrogen bonds. Antimicrobial activities of the complex were evaluated by minimum inhibitory concentration against gram-negative bacteria (E. coli, P. aeruginosa), molds (A. niger, P. citrinum) and yeasts (C. albicans, S. cerevisiae).

Mercury(II) cyanide complexes with alkyldiamines: solid-state/solution NMR, computational, and antimicrobial studies

Mercury cyanide complexes of alkyldiamines (1–6), [Hg(L)(CN)2] (where L = en (1,2-diaminoethane), pn (1,3-diaminopropane), N-Me-en, N, N′-Me2-en, N, N′-Et2-en, and N, N′-ipr2-en), have been synthesized and characterized by elemental analysis, IR, 13C, and 15N solution NMR in DMSO-d6, as well as 13C, 15N, and 199Hg solid-state NMR spectroscopy. Complexes 1 and 2 have been studied computationally, built and optimized by GAUSSIAN03 using DFT at B3LYP level with LanL2DZ basis set. Binding modes of en and bn (where bn = 1,4-diaminobutane) toward Hg(CN)2 are completely different. Complexes with en and pn show chelating binding to Hg(II), while bn behaves as a bridging ligand to form a polymeric structure, [Hg(CN)2-bn]∞ [B.A. Al-Maythalony, M. Fettouhi, M.I.M. Wazeer, A.A. Isab. Inorg. Chem. Commun., 12, 540 (2009).]. The solution 13C NMR of the complexes demonstrates a slight shift of the −C≡N (0.9 to 2 ppm) and −C–NH2 (0.25 to 6 ppm) carbon resonances, while the other resonances are relatively unaffected. 15N labeling studies have shown involvement of alkyldiamine ligands in coordination to the metal. The principal components of the 13C, 15N, and 199Hg shielding tensors have been determined from solid-state NMR data. Antimicrobial activity studies show that the complexes exhibit higher antibacterial activities toward various microorganisms than Hg(CN)2.