Joydev Dinda

Cyclopalladation versus hydroxylation. A case of pH dependence

Alkyl-2-(naphthyl--azo)imidazoles (NaiR, 2 )( C 10H7NNC3H2N21R; R= Me (a), Et (b), PhCH2 (c)) have been reacted with Na2PdCl4 in MeOH or MeCN solutions of Pd(MeCN)2Cl2 to synthesise Pd(NaiR)Cl2 (3). The reaction of Pd(OAc)2 in boiling benzene with NaiR followed by the addition of LiCl has resulted in the synthesis of the cyclopalladated complex Pd(NaiRH)Cl (4). The ligand, NaiR, acts as a N,N-bidentate chelator while NaiRH acts as a tridentate N,N,C-cyclometallat- ing ligand. The infrared spectra of 3 exhibit two PdCl stretches correspond to a cis-PdCl2 geometry, and a single (PdCl) band in 4 suggests one PdCl bond. Cyclopalladation is supported by a single crystal X-ray crystal structural study of Pd(NaiEtH)Cl (4b) and the metallation takes place at C(8)-position. The solution of Pd(NaiR)Cl2 (3) is also irreversibly transformed into Pd(NaiRH)Cl (4) when the pH is adjusted to 4.5-6.0 by NaOAc or other bases (NaOMe, NaOH, LiOH, Li2CO3 etc.). At higher pH values (8-10) the reaction shows the chelative hydroxylation at the C(2)-site to synthesise Pd(NaiRO)Cl (5). The structure of the hydroxylated blue product is also supported by a single crystal X-ray crystal structure of Pd(NaiEtO)Cl (5b). The reaction of Pd(NaiR)Cl2 in MeCN with dilute sodium hydroxide in air, or aqueous silver nitrate under boiling conditions, or its treatment with Tollens reagent in MeCN solution under ambient conditions has also yielded the hydroxylated product. All the compounds have been characterised by elemental analyses, IR, UV-vis and 1 H-NMR data. The solution spectral behaviour has been interpreted by EHMO calculations.

Naphthylazoimidazole and mercury(II) complexes. Single crystal X-ray structure of 1-ethyl-2-(naphthyl-α-azo)imidazolium hexaflurophosphate

Abstract 1-Alkyl-2-(naphthyl-(α/β)-azo)imidazole [α-NaiR (2)/β-NaiR (3); R=Me (a), Et (b), CH2Ph (c)] are N,N′-bidentate chelating ligands. The structure of 1-ethyl-2-(naphthyl-α-azo)imidazolium hexaflurophosphate has been confirmed by single crystal X-ray structure study and shows supramolecular geometry through non-covalent interactions (C–H⋯F, C–H⋯π, π⋯π). Mercury(II) complexes of the formula Hg(NaiR)Cl2 (4/5) have been synthesised and characterised by spectral (IR, UV–Vis and 1H and 13C NMR) studies. α-NaiR has been used to synthesise organomercury derivatives, Hg(α-NaiR–H)Cl (6) and the site of mercuration has been supported by charge density calculation using a semi-empirical PM3 technique.

Copper(I)–azoimidazoles: a comparative account on the structure and electronic properties of copper(I) complexes of 1-methyl-2-(phenylazo)imidazole and 1-alkyl-2-(naphthyl-(α/β)-azo)imidazoles

Abstract Bis-[1-alkyl-2-(naphthyl-(α/β)azo)imidazole]copper(I) perchlorate derivatives, [Cu(α-NaiR)2(ClO4)] and Cu(β-NaiR)2](ClO4), have been characterised by spectral and electrochemical studies. The single crystal X-ray structure of bis-[1-ethyl-2-(naphthyl-α-azo)imidazole]copper(I) perchlorate shows strong bonding with two imidazole-N atoms, two azo-N donors interact weakly and the structure is described as having a [2+2] distorted linear geometry. A structural comparison has been done with the X-ray structure of bis-[1-methyl-2-(phenylazo)imidazole]copper(I) perchlorate which is Td symmetric. Solution electronic spectra and redox properties are compared and have been correlated with EHMO calculation.

Au(I)- and Pt(II)-N-heterocyclic carbene complexes with picoline functionalized benzimidazolin-2-ylidene ligands; synthesis, structures, electrochemistry and cytotoxicity studies

Novel Au(I)-N-heterocyclic carbene complexes, 1-methyl-3-(2-pyridylmethyl)-benzimidazolylidenegold(I)-chloride, 1; 1-benzyl-3-(2-pyridylmethyl)-benzimidazolylidenegold(I)chloride, 2; and Pt(II)-N-heterocyclic carbene complexes 1-methyl-3-(2-pyridylmethyl) benzimidazolylidene platinum(II)chloride, 3; and 1-benzyl-3-(2-pyridylmethyl) benzimidazolylidene platinum-(II)chloride, 4, have been synthesized, based on CN-donor proligands 1-alkyl-3-(2-pyridylmeth-yl)-benzimidazoliumchloride L1 and L2 [alkyl, R = –CH3 = L1; R = –CH2Ph = L2]. All the compounds have been synthesized and characterized by different spectroscopic methods. The Au(I) complexes 1 and 2 have been synthesized by a silver carbene transfer method. The solid-state structures of 1 and 3 have been determined by single crystal X-ray diffraction studies. The square planar Pt(II) complexes 3 and 4 show a reversible Pt(II)/Pt(IV) couple at 0.69 eV and 0.67 eV respectively. Among the complexes 1–4, complexes 1 and 3 have been used for cytotoxicity studies on the cell lines B16F10 (mouse melanoma), HepG2 (human hepatocarcinoma) and HeLa (human cervical carcinoma). IC50 values are compared with cisplatin, among 1 and 3, the Au(I) complex 1 is more effective than Pt(II) complex 3.

N, N′-Olefin Functionalized Bis-Imidazolium Gold(I) Salt Is an Efficient Candidate to Control Keratitis-Associated Eye Infection

Keratitis treatment has become more complicated due to the emergence of bacterial or fungal pathogens with enhanced antibiotic resistance. The pharmaceutical applications of N-heterocyclic carbene complexes have received remarkable attention due to their antimicrobial properties. In this paper, the new precursor, 3,3′-(p-phenylenedimethylene) bis{1-(2- methyl-allyl)imidazolium} bromide (1a) and its analogous PF6 salt (1b) were synthesized. Furthermore, silver(I) and gold(I) -N-heterocyclic carbene (NHC) complexes [Ag2LBr2/Au2LBr2; 2a/3a], [(Ag2L2)(PF6)2/(Au2L2)(PF6)2; 2b/3b] were developed from their corresponding ligands. All compounds were screened for their antimicrobial activities against multiple keratitis-associated human eye pathogens, including bacteria and fungi. Complexes 2a and 3a showed highest activity, and the effectiveness of 3a was also studied, focusing eradication of pathogen biofilm. Furthermore, the structures of 1a, 2a and 3b were determined using single crystal X-ray analysis, 2b and 3a were optimized theoretically. The mechanism of action of 3a was evaluated by scanning electron microscopy and docking experiments, suggesting that its target is the cell membrane. In summary, 3a may be helpful in developing antimicrobial therapies in patients suffering from keratitis-associated eye infections caused by multidrug-resistant pathogens.

Synthesis, structure and electrochemical behaviour of Ru(II)- and Pt(II)-carbene complexes of the NCN-pincer 1,3-bis(2-pyridylmethyl)-1H-benzimidazolium chloride

Novel NCN-pincer carbene complexes of Ru(II), 1,3-bis(2-pyridylmethyl)benzimidazolineruthenium(II) bishexafluorophosphate (2), and Pt(II), 1,3-bis(2-pyridylmethyl)benzimidazolinechloroplatinum(II) hexafluorophosphate (3), complexes based on 1,3-bis(2-pyridylmethyl)-1H-benzimidazolium chloride (1) were synthesized and characterized by different spectroscopic methods. Complex 2 shows an absorption maximum at 386 nm, blue-shifted in comparison to Ru(bpy)32+ and Ru(tpy)22+, probably due to the strong σ-donor and weak π-acceptor properties of the electron-rich NHC ligand. Electrochemical studies show Ru(II)/Ru(III) and Pt(II)/Pt(IV) reversible couples at 0.67 and 0.58 eV, respectively, lower than those for the analogous complexes of ligands like bipyridine (bpy), terpyridine (tpy) and phenylbipyridine (pbpy). The solid state structure of 2 was solved by X-ray diffraction. Theoretical studies (B3LYP/LANL2DZ) of the complex show a HOMO (−0.38594 au) mainly centered on the ruthenium and benzimidazole, whereas the LUMO (−0.25130 au) is populated by pyridines. Therefore, it is assumed that the charge transfer from HOMO → LUMO is mixed ILCT (interligand charge transfer)/MLCT (metal to ligand charge transfer). The observed lower redox potentials of the Pt(II) complex compared to the Ru(II) complex is supported by theoretically calculated ionisation potentials and also electron affinity values. To the best of our knowledge, 2 is the first example of a six-membered metallacycle homoleptic chelate pincer NCN–Ru(II) N-heterocyclic carbene complex.

Gold (I) N-heterocyclic carbene complex inhibits mouse melanoma growth by p53 upregulation.

BackgroundCancer treatment using gold (I) complexes is becoming popular. In this study, a gold (I) N-heterocyclic complex designated as complex 3 was synthesized, its cytotoxicity was examined, and its anti-melanoma activity was evaluated in vitro and in vivo.MethodsViability of cancer cells was determined by MTT assay upon treatment with various concentrations of a gold (I) N-heterocyclic carbene complex (complex 3) in a dose and time dependent manner. Mouse melanoma cells B16F10 were selected for further apoptotic studies, including flowcytometric analysis of annexin binding, cell cycle arrest, intracellular ROS generation and loss in the mitochondrial membrane potential. ELISA based assays were done for caspase activities and western blots for determining the expression of various survival and apoptotic proteins. Immunocytology was performed to visualize the translocation of p53 to the nucleus. B16F10 cells were inoculated into mice and post tumor formation, complex 3 was administered. Immunohistology was performed to determine the expressions of p53, p21, NF-κB (p65 and p50), MMP-9 and VEGF. Student’s t test was used for determining statistical significance. The survival rate data were analyzed by Kaplan-Meier plots.ResultsComplex 3 markedly inhibited the growth of HCT 116, HepG2, and A549, and induced apoptosis in B16F10 cells with nuclear condensation, DNA fragmentation, externalization of phosphatidylserine, activation of caspase 3 and caspase 9, PARP cleavage, downregulation of Bcl-2, upregulation of Bax, cytosolic cytochrome c elevation, ROS generation, and mitochondrial membrane potential loss indicating the involvement of an intrinsic mitochondrial death pathway. Further, upregulation of p53, p-p53 (ser 15) and p21 indicated the role of p53 in complex 3 mediated apoptosis. The complex reduced tumor size, and caused upregulation of p53 and p21 along with downregulation of NF-κB (p65 and p50), VEGF and MMP-9. These results suggest that it induced anti-melanoma effect in vitro and in vivo by modulating p53 and other apoptotic factors.ConclusionsThe gold (I) N-heterocyclic carbene complex (C22H26N6AuO2PF6) designated as complex 3 induced ROS and p53 dependent apoptosis in B16F10 cells involving the mitochondrial death pathway along with suppression of melanoma tumor growth by regulating the levels of pro and anti apoptotic factors (p53, p21, NF-κB, VEGF and MMP-9).

Pyrazine Functionalized Ag(I) and Au(I)-NHC Complexes are Potential Antibacterial Agents

Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Bacteria can develop ways to render traditional antibiotics ineffective, raising a crucial need to find new antimicrobials with novel mode of action. We demonstrate here a novel class of pyrazine functionalized Ag(I) and Au(I)-NHC complexes as antibacterial agents against human pathogens that are resistant to several antibiotics. Complete synthetic and structural studies of Au(I) and Ag(I) complexes of 2-(1-methylimidazolium) pyrimidinechloride (L-1), 2,6-bis(1-methylimidazol)pyrazinechloride (L-2) and 2,6-bis(1-methyl imidazol) pyrazinehexa-fluorophosphate (L-3) are reported herein. Chloro[2,6-bis(1-methyl imidazol)pyrazine]gold(I), 2b and chloro [2,6-bis(1-methyl imidazol)pyrazine]silver(I), 2a complexes are found to have more potent antimicrobial activity than other synthesized compounds and several conventionally used antibiotics. Complexes 2b and 2a also inhibit the biofilm formation by Gram-positive bacteria, Streptococcus mutans and Gram-negative bacteria, Escherichia coli, causing drastic damage to the bacterial cell wall and increasing membrane permeability. Complexes 2b and 2a strongly binds to both Lys and Dap-Type peptidoglycan layers, which may be the reason for damage to the bacterial cell wall. Theoretical studies of all the complexes reveal that 2b and 2a are more reactive than other complexes, and this may be the cause of differences in antibacterial activity. These findings will pave the way towards developing a new class of antibiotics against different groups of conventional antibiotic-resistant bacteria.

Carbazole functionalized luminescent silver(I), gold(I) and gold(III)–N-heterocyclic carbene complexes: a new synthetic disproportionation approach towards Au(I)–NHC to provide Au(III)–NHC

Synthetic, structural and photophysical properties of carbazole functionalized novel procarbenic species 1-(methyl/picolyl)-3-(N-ethylcarbazolyl)-1H benzimidazoliumhexaflurophosphate (1 and 2) and their N-heterocyclic carbene (NHC) complexes of Ag(I) (3 and 4), Au(I) (5 and 6) and Au(III) (7 and 8) are described. According to the solid-state structures, a linear coordination geometry of Ag(I)–NHC (4) and Au(I)–NHC (6) has been established by X-ray diffraction studies; whereas the Au(III)–NHC complex (7) adopts the square planar geometry. The Au(III)–NHC (7 and 8) complexes have been synthesized from Au(I)–NHC (5 and 6) by capitalizing on a novel disproportionation protocol. Furthermore, the Au–Ccarbene bonds in complexes 7 and 8 are inert towards changes in the oxidation state of the metal atom. All the proligands (1 and 2) and complexes (3–8) are luminescent at room temperature.

N-heterocyclic carbene supported Au(I) and Au(III) complexes: a comparison of cytotoxicities

The N-heterocyclic carbene (NHC) precursor 2-pyridin-2-yl-2H-imidazo[1,5-a]pyridin-4-ylium hexafluorophosphate (1·HPF6) was used to synthesize various Ag and Au complexes, including [Ag(1)2][PF6] (2), [Au(1)2][PF6] (3) and [Au(1)Cl3] (4). The structure of the silver(I) complex 2 was established via NMR spectroscopy, mass spectrometry and single crystal X-ray crystallography. The gold(I)–NHC complex 3 was synthesized via transmetallation of the aforementioned silver complex and characterized using various spectroscopic methods. Treatment of 3 with Au(SMe2)Cl afforded 4, ostensibly via a disproportionation process. Close inspection of the solid state structure of 2 revealed that the Ag(I) center adopted a linear geometry; in contrast, a square planar geometry was observed for the solid structure of 4. The cytotoxicities of the gold complexes 3 and 4 were tested in vitro against Human colorectal carcinoma (HCT 116), Human hepatocellular carcinoma (HepG2), Human breast adenocarcinoma (MCF-7) and Murine melanoma (B16F10). The measured IC50 values showed that the Au(I) complex 3 was more potent than the Au(III) complex 4 as well as cisplatin.