Diorganotin(IV) N-acetyl-l-cysteinate complexes: Synthesis, solid state, solution phase, DFT and biological investigations

Diorganotin(IV) complexes of N-acetyl-l-cysteine (H₂NAC; (R)-2-acetamido-3-sulfanylpropanoic acid) have been synthesized and their solid and solution-phase structural configurations investigated by FTIR, Mössbauer, ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy. FTIR results suggested that in R₂Sn(IV)NAC (R = Me, Bu, Ph) complexes NAC²⁻ behaves as dianionic tridentate ligand coordinating the tin(IV) atom, through ester-type carboxylate, acetate carbonyl oxygen atom and the deprotonated thiolate group. From ¹¹⁹Sn Mössbauer spectroscopy it could be inferred that the tin atom is pentacoordinated, with equatorial R₂Sn(IV) trigonal bipyramidal configuration. In DMSO-d₆ solution, NMR spectroscopic data showed the coordination of one solvent molecule to tin atom, while the coordination mode of the ligand through the ester-type carboxylate and the deprotonated thiolate group was retained in solution. DFT (Density Functional Theory) study confirmed the proposed structures in solution phase as well as the determination of the most probable stable ring conformation. Biological investigations showed that Bu₂SnCl₂ and NAC2 induce loss of viability in HCC cells and only moderate effects in non-tumor Chang liver cells. NAC2 showed lower cytotoxic activity than Bu₂SnCl₂, suggesting that the binding with NAC²⁻ modulates the marked cytotoxic activity exerted by Bu₂SnCl₂. Therefore, these novel butyl derivatives could represent a new class of anticancer drugs.     

New mononuclear organotin(IV) 4-benzhydrylpiperazine-1-carbodithioates: Synthesis, spectroscopic characterization, X-ray structures and in vitro antimicrobial activities

A new series of organotin(IV) complexes with 4-benzhydrylpiperazine-1-carbodithioate (L) were synthesised by the metathesis reactions of the ligand-salt with triorganotin(IV) chlorides and diorganotin(IV) dichlorides in the appropriate molar ratio. All the complexes were characterized by elemental analysis, Raman, IR, and multinuclear NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopy. Solid-state studies (Raman, IR and X-ray analysis) confirmed the bidentate coordination of the ligand in all cases. Multinuclear NMR spectroscopy suggested that some tri- and diorganotin complexes reduce their geometry by one unit in solution. The τ values, 0.6 and 0.24 for chlorodibutyl- and chlorodiethyltin(IV) derivatives, respectively, authenticated the trigonal bipyramidal geometry for the first complex and distorted square-pyramidal geometry for the latter. The low τ value for the chlorodiethyltin(IV) complex is attributed to the additional Sn···Cl and Sn···S intermolecular interactions. The antimicrobial results indicated the compounds are active biologically.     

N-methyl-bis(2-bromo 6-pyridylmethyl)amine: high yield synthesis, and spectroscopic properties of the dichloroferrous complex with trigonal bipyramidal geometry

The new tridentate title ligand has been synthesized by a very convenient and high yield method. The dichloroferrous derivative was prepared in order to provide spectroscopic bases for solution studies of trigonal bipyramidal derivatives with aminomethylpyridyl containing ligands. Its crystal structure is reported, together with UV-Vis, ¹H NMR and molecular conductivity data. The absence of any MLCT in UV-Vis, significant broadening of the β and β′ resonances in ¹H NMR and neutral electrolytic behavior are reported and taken together, these parameters can now unequivocally serve as criteria to detect any tridentate coordination mode of the tripod in the chemistry of dichloroferrous complexes with tris-(2-pyridylmethyl)amine type ligands.     

Synthesis and in Vitro Antimicrobial Activity Screening of New 3‐Acetyl‐2,5‐disubstituted‐1,3,4‐oxadiazoline Derivatives

Thirteen new 3‐acetyl‐2,5‐disubstituted‐1,3,4‐oxadiazoline derivatives were synthesized from corresponding hydrazide‐hydrazones of isonicotinic acid in the reaction with acetic anhydride. The obtained compounds were identified with the use of spectral methods (IR, ¹H‐NMR, ¹³C‐NMR, MS). In vitro antimicrobial activity screening of synthesized compounds against a panel of bacteria and fungi revealed interesting antibacterial and antifungal activity of tested 1,3,4‐oxadiazoline derivatives, which is comparable to that of commonly used antimicrobial agents.     

Synthesis and antitumor activity of a new mixed-ligand complex di-n-butyl-(4-chlorobenzohydroxamato)tin(IV) chloride

Reaction of di-n-butyltin(IV) dichloride with 4-chlorobenzohydroxamic acid at 1:1 ratio yielded a new mixed-ligand diorganotin(IV) complex, di-n-butyl-(4-chlorobenzohydroxamato)tin(IV) chloride(DBDCT). It was fully characterized by IR, ¹H, ¹³C, ¹¹⁹Sn NMR spectra and single crystal X-ray analysis. In DBDCT, the tin atom is five-coordinated in a trigonal bipyramidal geometry. DBDCT exhibited strong in vitro cytotoxic activity toward human immature granulocyte leukemia (HL-60), human salivary-gland carcinoma (SGC-7901), human henrietta carcinoma (Hela) and human urinary bladder (T24) cell lines which, in some cases, were equal to, or even higher than those of cis-dichlorodiammineplatinum(II) (cisplatin, DDP), the widely clinically used drug. The further in vivo antitumor tests of DBDCT towards the transplantation tumor models of sarcoma carcinoma (S₁₈₀), hepatocellular carcinoma (H₂₂) and Ehrlich’s ascites carcinoma (EAC) on mice were carried out via injection intraperitoneally with cisplatin as positive contrast drug. The results showed that DBDCT displayed in vivo antitumor activity against the hepatocellular carcinoma H₂₂ and sarcoma carcinoma S₁₈₀ which were close to those of cisplatin, meanwhile, the survival-extending rates at middle dose and high dose on mice Ehrlich’s ascites tumor EAC were higher than those of cisplatin, and there was a good dose-effect relationship.     

Synthesis and structural studies on silvertin complex salts with cis-1,2-bis(diphenylphosphino)ethylene

Three new silver—tin complex salts with cis-1,2-bis(diphenylphosphino)ethylene have been synthesized. IR,³¹P and ¹¹⁹Sn NMR and conductivity data are reported and discussed together with the X-ray crystal structure of one of them, [Ag(cdppet)₂][SnPh₃(NO)₃)₂]. The silver atom is distorted tetrahedrally surrounded by the four phosphorus atoms of the two cdppet ligands. The tin atom is in a slightly distorted trigonal bipyramidal geometry with the phenyl carbon atoms in the equatorial plane and two oxygen atoms from monodentate nitrate groups at the apices.     

Synthesis and crystal structure of a new macrocyclic dimethyltin(IV) complex with 5-phenyl-1,3,4-oxadiazole-2-thiol linked by intermolecular CS?O non-bonded weak interactions

A new macrocycle dimethyltin(IV) complex 1 has been synthesized by the reaction of 5-phenyl-1,3,4-oxadiazole-2-thiol with dimethyltin dichloride in the presence of sodium ethoxide. The complex 1 has been characterized by elemental, IR, ¹H, ¹³C, ¹¹⁹Sn NMR spectra and X-ray crystallography diffraction analyses. X-ray data reveal that a 24-membered macrocycle associated by intermolecular CS?O non-bonded weak interactions. The geometry about each tin atom involved is distorted trigonal bipyramidal.     

Organometallic complexes with biological molecules. XVII. Triorganotin(IV) complexes with amoxicillin and ampicillin

Novel triorganotin(IV) complexes of two beta-lactamic antibiotics, 6-[D-(-)-beta-amino-p-hydroxyphenyl-acetamido]penicillin (=amoxicillin) and 6-[D-(-)-alpha-aminobenzyl]penicillin (=ampicillin), have been synthesized and investigated both in solid and solution states. The complexes corresponded to the general formula R(3)Sn(IV)antib*H(2)O (R=Me, n-Bu, Ph; antib=amox=amoxicillinate or amp=ampicillinate). Structural investigations about configuration in the solid state have been carried out by interpreting experimental IR and 119Sn M?ssbauer data. In particular, IR results suggested polymeric structures both for R(3)Sn(IV)amox.H(2)O and R(3)Sn(IV)amp*H(2)O. Moreover, both antibiotics appear to behave as monoanionic bidentate ligands coordinating the tin(IV) atom through ester-type carboxylate, as well as through the beta-lactamic carbonyl. Evidence that in none of these compounds water molecules were involved in coordination, was provided by thermogravimetric investigations. On the basis of 119Sn M?ssbauer spectroscopy it can be inferred that tin(IV) was pentacoordinate in all of the complexes in the solid state, showing an equatorial R(3)Sn(IV) trigonal bipyramidal (tbp) configuration. The nature of the complexes in solution state was investigated by using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, while an 119Sn spectrum was obtained for n-Bu(3)Sn(IV)amp*H(2)O. Although 1H- and 13C-NMR measurements suggested that in dimethyl sulfoxide (DMSO)-d(6) solution the polymeric structure collapsed, due to a solvolysis process of the beta-lactamic carbonyl bonding to the organometallic moiety, the complexes have been shown to maintain the same trigonal bipyramidal configuration at tin(IV) atom by the coordination of a DMSO molecule. Cytotoxic activity of these novel semisynthetic antibiotic derivatives has been tested towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia) using two different chromosome-staining techniques such as Giemsa and CMA(3). The occurrence of typical colchicinized-like (c-like) mitoses on slides obtained from animals exposed to organotin compounds, directly confirmed the high mitotic spindle-inhibiting potency of these chemicals. In addition, by comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the triorganotin(IV) complexes, structural damages such as 'achromatic lesions' and 'chromosome breakages' have been identified.     

Nitrosyl complexes of cobalt with hybrid bidentate ligands containing phosphorus and sulfur donor atoms

Nitric oxide reacts with [Co(PSR)₂](BF₄)₂ (PSR  1-(thioalkyl)-2-(diphenylphosphino)ethane) to form five-coordinate mononitrosyl {CoNO}⁸ complexes. On the basis of infrared and NMR data the [Co(NO)(PSR)₂]²⁺ cations are believed to have a trigonal–bipyramidal geometry, with a linear Co–NO linkage. The mononitrosyl derivatives disproportionate in solution giving [Co(NO)₂(PSR)₂]⁺ species, and probably Co(III) compounds. The stoichiometry of this reaction was examined in different solvents and in the presence of added halide or pseudohalide ions by NMR and IR techniques. The cobalt(III) complex [Co(NCS)₂(PSEt)₂]BF₄ has been isolated and characterized.     

Design,synthesis and anticancer activity of N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives

Novel N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives were designed, synthesized and their chemical structures were confirmed by ¹H NMR, ¹³C NMR and Mass spectra. The anticancer activities of the newly synthesized compounds were evaluated in vitro against three human cancer cell lines including K562, Colo-205 and MDA-MB 231 by MTT assay. The screening results showed that five compounds (16b, 16d, 16i, 16p and 16q) exhibited potent cytotoxic activities with IC₅₀ values between 20 and 40 μM. Further in vitro studies revealed that inhibition of sirtuins could be the possible mechanism of action of these molecules.     

Synthesis, characterization, crystal structures and in vitro antistaphylococcal activity of organotin(IV) derivatives with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine

New organotin(IV) complexes of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp) with 1:1 and/or 1:2 stoichiometry were synthesized and investigated by X-ray diffraction, FT-IR and ¹¹⁹Sn Mössbauer in the solid state and by ¹H and ¹³C NMR spectroscopy, in solution. Moreover, the crystal and molecular structures of Et₂SnCl₂(dbtp)₂ and Ph₂SnCl₂(EtOH)₂(dptp)₂ are reported. The complexes contain hexacoordinated tin atoms: in Et₂SnCl₂(dbtp)₂ two 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine molecules coordinate classically the tin atom through N(3) atom and the coordination around the tin atom shows a skew trapezoidal structure with axial ethyl groups. In Ph₂SnCl₂(EtOH)₂(dptp)₂ two ethanol molecules coordinate tin through the oxygen atom and the 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N(3), to the OH group of the ethanol moieties; Ph₂SnCl₂(EtOH)₂(dptp)₂ has an all-trans structure and the C-Sn-C fragment is linear. On the basis of Mössbauer data, the 1:2 diorganotin(IV) complexes are advanced to have the same structure of Et₂SnCl₂(dbtp)₂, while Me₂SnCl₂(dptp)₂ to have a regular all-trans octahedral structure. A distorted cis-R₂ trigonal bipyramidal structure is assigned to 1:1 diorganotin(IV) complexes. The in vitro antibacterial activities of the synthesized complexes have been tested against a group of reference pathogen micro-organisms and some of them resulted active with MIC values of 5 μg/mL, most of all against staphylococcal strains, which shows their inhibitory effect.     

Potentiality of organotin(IV) compounds in the control of foliar blight disease of wheat (Triticum aestivum) caused by Bipolaris sorokiniana

Three different types of eight organotin(IV) compounds (of which four were newly synthesised) were screened against Bipolaris sorokiniana. The new compounds were characterised by elemental, IR, ¹H and ¹³C NMR spectral analyses. The experiments were carried out in the field and laboratory between the months of November 2006 to March 2007 and November 2007 to March 2008 at Uttar Banga Krishi Viswavidyalaya, Cooch Bihar, W.B., India. All of the organotin(IV) compounds were tested for the toxicity assay against Indian wheat (Triticum aestivum L.), cv. Sonalika. The spore germination and growth of B. sorokiniana and the biochemical changes associated with the induction of resistance by these chemicals were also tested. The influence of the organic groups (attached to tin atom) of the three different types of compounds studied on the fungicidal activity is remarkably distinct. Some of the compounds tested are more active in controlling the fungus than a commonly used commercial product.     

4,5-Dihydro-1H-pyrazolo[3,4-d]pyrimidine containing phenothiazines as antitubercular agents

A series of novel dihydropyrazolo[3,4-d]pyrimidine derivatives bearing a phenothiazine nucleus were synthesized in excellent yields via a modified Biginelli multicomponent reaction. The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, Mass spectra and elemental analysis followed by antimycobacterial screening. Among all the screened compounds, compound 4g showed most pronounced activity against Mycobacterium tuberculosis (Mtb) with minimum inhibitory concentration (MIC) of 0.02 μg/mL, making it more potent than first line antitubercular drug isoniazid.     

Coordination behaviour of biologically active benzothiazolines towards silicon(IV)

The synthesis and structural features of some trigonal bipyramidal and octahedral complexes of silicon(IV) with biologically active benzothiazolines are described. These were derived by the condensation of pyridine-2-aldehyde, furfuraldehyde, thiophene-2-aldehyde and indole-3-carbaldehyde with 2-mercaptoaniline. The newly synthesized complexes have been characterized by elemental analyses, conductance measurements, molecular weight determinations and electronic, infrared, ¹H and ¹³C NMR spectral studies. The ligand and its complexes of Si(IV) have been tested for their antifungal activity against Helmenthosporeum gramineum and Rhizopus oryzae. The growth inhibition percentage was calculated on the basis of the average diameter of the fungal colony.     

Complexes formed from 2,4,6-trimercaptotriazine (H3TMT): synthesis and structural characterization of [M(PhP(CH2CH2P(Ph)2)2(HTMT)], M=Ni(II), Pd(II), Pt(II)

Na₃TMT · 9H₂O (H₃TMT=2,4,6-trimercaptotriazine) reacts with M(PPP)Cl₂, PPP=PhP(CH₂CH₂PPh₂)₂, M=Ni, Pd, Pt, to give the compounds [M(PPP)(HTMT)]. The nickel and palladium complexes have been characterized by single-crystal X-ray diffraction analysis. PPP is tridentate in both complexes. The nickel complex has an irregular trigonal bipyramidal configuration in which the triazine is bidentate, coordinating through one sulfur and one nitrogen donor atom. The palladium complex has an approximately square planar geometry in which the triazine forms a strong Pd-S bond in the plane and also a very weak Pd-N interaction above the plane. The ³¹P NMR spectrum of the platinum complex is similar to that of the palladium complex, which is consistent with the Pt complex also having an approximately square-planar structure. Variable temperature NMR spectra show that two conformational isomers of the nickel complex are present in solution at low temperatures, though exchange is fast at room temperature. DFT calculations have confirmed the possible existence of two five-coordinate isomers of comparable stability.     

Water Soluble Coumarin Quaternary Ammonium Chlorides: Synthesis and Biological Evaluation

In the present study, coumarin‐bearing three pyridinium and three tetra‐alkyl ammonium salts were synthesized. The compounds were fully characterized by ¹H‐ and ¹³C‐NMR, LC/MS and IR spectroscopic methods and elemental analyses. The cytotoxic properties of all compounds were tested against human liver cancer (HepG2), human colorectal cancer (Caco‐2) and non‐cancer mouse fibroblast (L‐929) cell lines. Some compounds performed comparable cytotoxicity with standard drug cisplatin. Antibacterial properties of the compounds were tested against Gram‐negative Escherichia coli and Gram‐positive Bacillus subtilis bacteria, but the compounds did not have any antibacterial effect against both bacteria. Enzyme inhibitory properties of all compounds were tested on the activities of human carbonic anhydrase I and II, and xanthine oxidase. All compounds inhibited both enzymes more effectively than standard drugs, acetazolamide and allopurinol, respectively. The biological evaluation results showed that ionic and water soluble coumarin derivatives are promising structures for further investigations especially on enzyme inhibition field.     

119Sn Mössbauer spectroscopic studies of the products of the reaction of triorganotin(IV) derivatives with 6-thiopurine

A structural study of the products of the reaction of R₃Sn^IV derivatives (R = Me, Buⁿ, Ph) with 6-thiopurine, 6-TPH₂, and its sodium salt, 6-TPHNa, has been undertaken using Mössbauer spectroscopy and the point-charge model rationalization of the Mössbauer parameter nuclear quadrupole splitting. The synthetic reactions have been carried out at ca. 0 °C, 20 °C and 50 °C. The Mössbauer spectra of the complexes AlK₃Sn(6-TPH) are consistent with the occurrence of two distinct tin(IV) sites in samples prepared at the lower temperature, while one only site appears by increasing the temperature of the reaction. Two tin sites constantly occur in the products of the reactions involving the Ph₃Sn^IV moiety; the stoichiometry is assumed to be (Ph₃Sn)₃(6-TPH)(6-TP) for the uniquely-formed complex. Solid state polymeric structures with trigonal bipyramidal environments of the tin atoms and planar SnC₃ skeletons have been proposed. The apical ligand atoms have been assumed to be N, S and N, N in the samples showing two individual tin(IV) sites, and N, N when a single site was present.     

Transition metal complexes with pyrazole based ligands, part 18: new binuclear Cu(I), Cu(II) and Co(II) complexes with 3,5-dimethyl-1-thiocarboxamide pyrazole: synthesis, structural and magnetic studies

Three new binuclear metal complexes of the formulas (L = 3,5-dimethyl-1-thiocarboxamide pyrazole) have been synthesized and characterized by chemical analysis, FT-IR spectroscopy, solution conductivity, solid state magnetic measurements and X-ray single crystal and variable temperature powder diffraction. Complex 1 forms doubly chloro-bridged dimers, with Cu(II) in distorted trigonal bipyramidal coordination with the apical positions occupied by chlorine atoms. Magnetic measurements indicate an antiferromagnetic interaction between the Cu(II) centres in the dimer, with the singlet-triplet exchange parameter of J = −19.40 cm⁻¹. Complex 2 forms doubly sulfur-bridged dimers, with Cu(I) in distorted tetrahedral coordination with apical positions occupied by bromine atoms. Complex 3 is a cobalt analogue of 1. It contains dinuclear units formed by five-coordinate high-spin Co(II) in a distorted trigonal bipyramidal environment. The magnetisation of 3 shows no significant departure from Curie-Weiss behaviour between room temperature and 5 K. All crystal structures are stabilized by two-dimensional hydrogen bonding networks between the carboxamide nitrogen donors and the terminal halide acceptors.     

Synthesis,biological evaluation and molecular docking studies of aminochalcone derivatives as potential anticancer agents by targeting tubulin colchicine binding site

A series of aminochalcone derivatives have been synthesized, characterized by HRMS, ¹H NMR and ¹³C NMR and evaluated for their antiproliferative activity against HepG2 and HCT116 human cancer cell lines. The most of new synthesized compounds displayed moderate to potent antiproliferative activity against test cancer cell lines. Among the derivatives, compound 4 displayed potent inhibitory activity with IC₅₀ values ranged from 0.018 to 5.33 μM against all tested cancer cell lines including drug resistant HCT-8/T. Furthermore, this compound showed low cytotoxicity on normal human cell lines (LO2). The in vitro tubulin polymerization assay showed that compound 4 inhibited tubulin assembly in a concentration-dependent manner with IC₅₀ value of 7.1 μM, when compared to standard colchicine (IC₅₀ = 9.0 μM). Further biological evaluations revealed that compound 4 was able to arrest the cell cycle in G2/M phase. Molecular docking study demonstrated the interaction of compound 4 at the colchicine binding site of tubulin. All the results indicated that compound 4 is a promising inhibitor of tubulin polymerization for the treatment of cancer.     

Potentiometric and spectroscopic studies on the dimethyltin(IV) complexes of 2-hydroxyhippuric acid

Equilibrium and spectroscopic (1H, 13C NMR and 119Sn M?ssbauer) studies in aqueous solution are reported for dimethyltin(IV) complexes of 2-hydroxyhippuric acid (Sal-Gly). Below pH 4, oxygen-coordinated complexes MLH and ML are formed. In the pH range 5-8.5, the species MLH(-1), predominates at any metal-to-ligand ratio. The ligand exchange of this species is slow on the NMR time scale, which allows its structural characterization by NMR spectroscopy: the coordination polyhedron around the tin atom is distorted trigonal bipyramidal, with tridentate [O-,N-,COO-] coordination of Sal-Gly, involving two equatorial methyl groups. The NMR results reveal that the main cause of the distortion of the polyhedron is the large CH3-Sn-CH3 angle of 136+/-4 degrees. The presented results supplement the data available on the dimethyltin(IV)-promoted amide deprotonation of peptides, and provide further arguments for the fundamental role of the carboxylate as an anchoring group in this process.