Synthesis,cytotoxicity and antibacterial studies of symmetrically and non‐symmetrically benzyl‐ or p‐cyanobenzyl‐substituted N‐Heterocyclic carbene–silver complexes

From the reaction of 1H‐imidazole ( 1a ), 4,5‐dichloro‐1H‐imidazole ( 1b ) and 1H‐benzimidazole ( 1c ) with p‐cyanobenzyl bromide ( 2 ), symmetrically substituted N‐heterocyclic carbene (NHC) [( 3a–c )] precursors, 1‐methylimidazole ( 5a ), 4,5‐dichloro‐1‐methylimidazole ( 5b ) and 1‐methylbenzimidazole ( 5c ) with benzyl bromide ( 6 ), non‐symmetrically substituted N‐heterocyclic carbene (NHC) [( 7a–c )] precursors were synthesized. These NHC? precursors were then reacted with silver(I) acetate to yield the NHC‐silver complexes [1,3‐bis(4‐cyanobenzyl)imidazole‐2‐ylidene] silver(I) acetate ( 4a ), [4,5‐dichloro‐1,3‐bis(4‐cyanobenzyl)imidazole‐2‐ylidene] silver(I) acetate ( 4b ), [1,3‐bis(4‐cyanobenzyl)benzimidazole‐2‐ylidene] silver(I) acetate ( 4c ), (1‐methyl‐3‐benzylimidazole‐2‐ylidene) silver(I) acetate ( 8a ), (4,5‐dichloro‐1‐methyl‐3‐benzylimidazole‐2‐ylidene) silver(I) acetate ( 8b ) and (1‐methyl‐3‐benzylbenzimidazole‐2‐ylidene) silver(I) acetate ( 8c ) respectively. The four NHC‐precursors 3a–c, 7c and four NHC–silver complexes 4a–c and 8c were characterized by single crystal X‐ray diffraction. The preliminary antibacterial activity of all the compounds was studied against Gram‐negative bacteria Escherichia coli, and Gram‐positive bacteria Staphylococcus aureus using the qualitative Kirby‐Bauer disc‐diffusion method. All NHC–silver complexes exhibited medium to high antibacterial activity with areas of clearance ranging from 4 to 12 mm at the highest amount used, while the NHC‐precursors showed significantly lower activity. In addition, all NHC–silver complexes underwent preliminary cytotoxicity tests on the human renal‐cancer cell line Caki‐1 and showed medium to high cytotoxicity with IC₅₀ values ranging from 53 ( ± 8) to 3.2 ( ± 0.6) µM. Copyright © 2010 John Wiley & Sons, Ltd.     

N‐Phenyl‐substituted carbene precursors and their silver complexes: synthesis,characterization and antimicrobial activities

A series of unsymmetrically substituted N‐heterocyclic carbene (NHC) precursors ( 1a , 1b , 1c , 1d , 1e ) were synthesized from the reaction of N‐phenylbenzimidazole with various alkyl halides. These compounds were used to synthesize NHC–silver(I) complexes ( 2a , 2b , 2c , 2d , 2e ). The five new 1‐phenyl‐3‐alkylbenzimidazolium salts ( 1a , 1b , 1c , 1d , 1e ) and their NHC–silver complexes ( 2a , 2b , 2c , 2d , 2e ) were characterized by the ¹H NMR, ¹³C NMR and FT‐IR spectroscopic methods and elemental analysis techniques. Also, the two NHC–silver complexes 2b and 2c were characterized by single‐crystal X‐ray crystallography, which confirmed the linear C―Ag―Cl arrangements. The antibacterial activities of the NHC precursor and NHC–silver complexes were tested against three Gram‐positive bacterial strains (Bacillus subtilis, Listeria monocytogenes and Staphylococcus aureus) and three Gram‐negative bacterial strains (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) using the microdilution broth method. The NHC–silver complexes showed higher antibacterial activity than the NHC precursors. In addition, silver complexes 2a , 2b , 2c , 2d showed high antibacterial activity against the Gram‐positive bacteria L. monocytogenes and S. aureus compared to the standard, tetracycline. Copyright © 2014 John Wiley & Sons, Ltd.     

Non–symmetrically p–nitrobenzyl–substituted N–heterocyclic carbene–silver(I) complexes as metallopharmaceutical agents

In the present work, a series of eight new imidazole, 4,5–dichloroimidazole, 4,5–diphenylimidazole and benzimidazole based nitro–functionalized mono–N –heterocyclic carbene (NHC)–silver(I) acetate ( 7a–d ) and bis–NHC–silver(I) hexafluorophosphate complexes ( 8a–d ) were synthesised by the reaction of the corresponding azolium hexafluorophosphate salts ( 6a–d ) with silver(I) acetate and silver(I) oxide in methanol and acetonitrile, respectively. All the synthesised compounds were fully characterized by various spectroscopic techniques and elemental analyses. Additionally, the structure of bis–(1–benzyl–3–(p –nitrobenzyl)–4,5–dichloroimidazole–2–ylidene)silver(I) hexafluorophosphate complex ( 8b ) was confirmed by single crystal X–ray diffraction analysis. Preliminary in vitro antibacterial evaluation was conducted for all the compounds ( 6a–d) , ( 7a–d) , and ( 8a–d) by Kirby–Bauer's disc diffusion method followed by the determination of Minimum Inhibitory Concentration (MIC) from broth macrodilution method against five standard bacteria; two Gram–positive bacterial strains (Staphylococcus aureus and Bacillus subtilis) and three Gram–negative bacterial strains ( Escherichia coli , Shigella sonnei, and Salmonella typhi). All the hexafluorophosphate salts ( 6a – d) were found inactive against the tested bacterial strains and their corresponding mono– and bis–NHC–silver(I) complexes ( 7a–d and 8a–d ) exhibited moderate to high antibacterial activity with MIC value in the range 8–128 μg/mL. In addition, preliminary in vitro anticancer potential of all the silver(I) complexes ( 7a–d and 8a–d ) was determined against the human derived breast adenocarcinoma cells (MCF 7) by MTT assay. All the mono– and bis–NHC–silver(I) complexes ( 7a–d and 8a–d ) orchestrated high anticancer potential with IC₅₀ values ranging from 10.39 to 59.56 nM. In comparison, mono– NHC–silver(I) complexes performed better than the bis–NHC–silver(I) complexes.     

Synthesis,Cytotoxicity and Antibacterial Studies of Novel Symmetrically and Nonsymmetrically 4‐(Methoxycarbonyl)benzyl‐Substituted N‐Heterocyclic Carbene–Silver Acetate Complexes

From the reaction of 1H‐imidazole ( 1a ), 4,5‐dichloro‐1H‐imidazole ( 1b ), 1H‐benzimidazole ( 1c ), 1‐methyl‐1H‐imidazole ( 1d ), and 1‐methyl‐1H‐benzimidazole ( 1f ) with methyl 4‐(bromomethyl)benzoate ( 2 ), symmetrically and nonsymmetrically 4‐(methoxycarbonyl)benzyl‐substituted N‐heterocyclic carbene (NHC) precursors, 3a – 3f , were synthesized. These NHC precursors were then reacted with silver(I) acetate (AgOAc) to yield the NHC–silver acetate complexes (acetato‐κO){1,3‐bis[4‐(methoxycarbonyl)benzyl]imidazol‐2‐ylidene}silver ( 4a ), (acetato‐κO){4,5‐dichloro‐1,3‐bis[4‐(methoxycarbonyl)benzyl]‐2,3‐dihydro‐1H‐imidazol‐2‐yl}silver ( 4b ), (acetato‐κO){1,3‐bis[4‐(methoxycarbonyl)benzyl]‐2,3‐dihydro‐1H‐benzimidazol‐2‐yl}silver ( 4c ), (acetato‐κO){1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1H‐imidazol‐2‐yl}silver ( 4d ), (acetato‐κO){4,5‐dichloro‐1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1H‐imidazol‐2‐yl}silver ( 4e ), and (acetato‐κO){1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1H‐benzimidazol‐2‐yl}silver ( 4f ), respectively. The three NHC–AgOAc complexes 4a, 4c , and 4d were characterized by single‐crystal X‐ray diffraction. All compounds studied in this work were preliminarily screened for their antimicrobial activities in vitro against Gram‐positive bacteria Staphylococcus aureus, and Gram‐negative bacteria Escherichia coli using the qualitative disk‐diffusion method. All NHC–AgOAc complexes exhibited weak‐to‐medium antibacterial activity with areas of clearance ranging from 4 to 7 mm at the highest amount used, while the NHC precursors showed significantly lower activity. In addition, NHC–AgOAc complexes 4a and 4b , and 4d – 4f exhibited in preliminary cytotoxicity tests on the human renal‐cancer cell line Caki‐1 medium‐to‐high cytotoxicities with IC₅₀ values ranging from 3.3±0.4 to 68.3±1 μM .     

Benzimidazole‐based silver(I)–N‐heterocyclic carbene complexes as anti‐bacterials: synthesis,crystal structures and nucleic acids interaction studies

A series of new benzimidazolium salts as N‐heterocyclic carbene (NHC) precursors has been synthesized. Reactions of these salts with Ag₂O with varying metal‐to‐salt ratio facilitate the formation of a series of new binuclear and mononuclear Ag(I)–NHC complexes. All compounds were characterized using physicochemical and spectroscopic techniques. Single‐crystal X‐ray diffraction study reveals a binuclear structure for one of the complexes and a mononuclear one for two others. These complexes exist as cationic Ag(I)–NHC complexes with the chelation of carbene carbons to the silver centre in an almost linear manner. The compounds were screened for their anti‐bacterial activities against Staphylococcus aureus (ATCC 12600) as a Gram‐positive bacterium and Escherichia coli (ATCC 25922) as a Gram‐negative bacterium. The results show that both bacteria appear markedly inhibited. Furthermore, the results suggest the possibility of steric variation as a modulation of the anti‐bacterial activities. The nuclease activities of the compounds were assessed using gel electrophoresis and the results indicate that these complexes can cleave or degrade DNA and RNA via a non‐oxidative mechanism. Copyright © 2014 John Wiley & Sons, Ltd.     

Non-symmetrically p-nitrobenzyl- and p-cyanobenzyl-substituted N-heterocyclic carbene-silver(I) complexes: synthesis,characterization and antibacterial studies

Various nitro/nitrile-functionalized benzimidazol-2-ylidene carbene complexes of silver(I) (7a–d and 11a–d) were synthesized by combination of 1-allyl/1-isopropyl/1-sec-butyl/1-isopentyl-3-(nitro/cyano-benzyl)-3H-benzimidazol-1-ium hexafluorophosphate (6a–d and 10a–d) with silver(I) oxide in acetonitrile. The compounds were characterized by ¹H, ¹³C NMR, FT-IR, mass spectrometry, and elemental analysis. Additionally, the in vitro antibacterial activity of the N-heterocyclic carbene (NHC) precursors (6a–d and 10a–d) and their corresponding NHC-silver(I) complexes (7a–d and 11a–d) were investigated against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli using the qualitative Kirby-Bauer disk diffusion method. All the NHC-silver(I) complexes exhibited medium-to-high antibacterial activity with areas of clearance ranging from 12 mm to 21 mm, while the NHC precursors were inactive against both strains of bacteria.     

Sulfonated N‐heterocyclic carbine‐silver (I) complexes: Synthesis,characterisation and biological evaluation

The synthesis, characterisation and biological activity of water‐soluble Ag(I)‐NHC complexes, general formula Na[(NHC)AgCl] where NHC is a sulfonated and sterically hindered N‐heterocyclic carbene, is reported. The Ag‐NHC complexes (2a–e) were synthesised by reacting the corresponding sulfonated NHC ligands with Ag₂O in the presence of NaCl or NaBr in methanol/water (1:1) solution. Synthesised silver (I)‐N‐heterocyclic carbene complexes have been characterised by NMR, micro‐analysis and HRMS spectroscopic methods. The IC₅₀ values of these complexes were determined by a proliferation BrdU enzyme‐linked immunosorbent assay (ELISA) against HeLa (human cervix carcinoma), HT29 (human adenocarcinoma) and L929 (mouse fibroblast) cell lines. These complexes have been highlighted as promising and original platforms for building new types of metalodrug. All new water‐soluble Ag(I) complexes demonstrated remarkable cytotoxic activity against HeLa, HT29 and L929 cell lines.     

Binuclear meta‐xylyl‐linked Ag(I)‐N‐heterocyclic carbene complexes of N‐alkyl/aryl‐alkyl‐substituted bis‐benzimidazolium salts: synthesis,crystal structures and in vitro anticancer studies

Salts of meta‐xylyl‐linked N‐ethyl/n‐butyl/benzyl‐substituted bis‐benzimidazolium having hexafluorophosphate counterions have been synthesized. The corresponding binuclear Ag(I)‐N‐heterocyclic carbene complexes were prepared by the reaction of Ag₂O. The N‐heterocyclic carbene (NHC) ligand precursor 7 and Ag(I)–NHC complexes 10 and 11 have been structurally characterized by single‐crystal X‐ray diffraction technique. All of the reported compounds have been tested for their anticancer activity using human colorectal (HCT 116) cancer cell lines. Sterically varied benzimidazolium salts displayed significant activity against HCT 116 cell line, yielding IC₅₀ values in the range 0.1–19.4 µ m , while Ag(I)–carbene complexes showed exceptionally good activity (0.2–1.3 µ m ) against tested cancer cell lines. Copyright © 2013 John Wiley & Sons, Ltd.     

Palladium(II) N-heterocyclic carbene complexes: synthesis,structures and cytotoxicity potential studies against breast cancer cell line

Abstract

Mononuclear trans-Pd(II)–NHC complexes (where NHC?=?N-heterocyclic carbene) bearing asymmetrically substituted NHC-ligand have been synthesized via transmetalation reaction between Ag(I)–NHC complexes and [Pd(NCCH₃)₂Cl₂]. The NHC precursors are accessible in two steps by N-n-alkyl reactions of benzimidazole. The resultant benzimidazolium salts were deprotonated with Ag₂O by in situ deprotonation to facilitate the formation of mononuclear Ag(I)–NHC complexes. Single-crystal structural study for Pd(II)–NHC shows that the palladium(II) ion exhibits a square-planar geometry of two NHC ligands and two chloride ions. The cytotoxicity study was investigated against breast cancer cell line (MCF-7). The Ag(I)–NHC complexes exhibit better activities than their corresponding Pd(II)–NHC complexes, whereas all benzimidazolium salts are inactive toward MCF-7 cancer cell line.     

Novel Benzyl‐ or 4‐Cyanobenzyl‐Substituted N‐Heterocyclic (Bromo)(carbene)silver(I) and (Carbene)(chloro)gold(I) Complexes: Synthesis and Preliminary Cytotoxicity Studies

N‐Heterocyclic carbene (NHC) complexes bromo(1,3‐dibenzyl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene)silver(I) ( 2a ), bromo[1‐(4‐cyanobenzyl)‐3‐methyl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene]silver(I) ( 2b ), and bromo[1‐(4‐cyanobenzyl)‐3‐methyl‐1,3‐dihydro‐2H‐benzimidazol‐2‐ylidene]silver(I) ( 2c ) were prepared by the reaction of 1,3‐dibenzyl‐1H‐imidazol‐3‐ium bromide ( 1a ), 3‐(4‐cyanobenzyl)‐1‐methyl‐1H‐imidazol‐3‐ium bromide ( 1b ), and 3‐(4‐cyanobenzyl)‐1‐methyl‐1H‐benzimidazol‐3‐ium bromide ( 1c ), respectively, with silver(I) oxide. NHC Complexes chloro(1,3‐dibenzyl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene)gold(I) ( 3a ), chloro[1‐(4‐cyanobenzyl)‐3‐methyl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene]gold(I) ( 3b ), and chloro[1‐(4‐cyanobenzyl)‐3‐methyl‐1,3‐dihydro‐2H‐benzimidazol‐2‐ylidene]gold(I) ( 3c ) were prepared via transmetallation of corresponding (bromo)(NHC)silver(I) complexes with chloro(dimethylsulfido)gold(I). The complex 3a was characterized in two polymorphic forms by single‐crystal X‐ray diffraction showing two rotamers in the solid state. The cytotoxicities of all three bromo(NHC)silver(I) complexes and three (chloro)(NHC)gold(I) complexes were investigated through 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bormide (MTT)‐based preliminary in vitro testing on the Caki‐1 cell line in order to determine their IC₅₀ values. (Bromo)(NHC)silver(I) complexes 2a – 2c and (chloro)(NHC)gold(I) complexes 3a – 3c were found to have IC₅₀ values of 27±2, 28±2, 34±6, 10±1, 12±5, and 12±3 μM , respectively, on the Caki‐1 cell line.     

Synthesis and crystal structures of sterically tuned ether functionalized NHC–silver(I) complexes: antibacterial and nucleic acid interaction studies

A series of new imidazolium salts (1–4) as N-heterocyclic carbene (NHC) precursors have been synthesized by successive N-alkylation method. Reactions of these salts with Ag₂O by varying the metal to salt ratio forms a series of new Ag(I)–NHC complexes (5–8). All compounds were characterized by physico-chemical and spectroscopic techniques. The molecular structures of 1 and 5 were characterized by single-crystal X-ray diffraction analysis. A comparative investigation of the bacterial growth inhibition potential of the salts and respective complexes indicates that 5–8 displayed good antibacterial activities on Staphylococcus aureus (ATCC 12600) and Escherichia coli (ATCC 11303) compared with the salts. Furthermore, it was observed that with increase in chain length at N-positions, the antibacterial activities also increased. Nuclease activity of the reported salts and Ag(I)–NHC complexes with nucleic acids (DNA and RNA) were also studied using agarose gel electrophoresis; the results show that the compounds do not have any apparent interaction with nucleic acids in the absence of hydrogen peroxide (H₂O₂). However, 5 and 8 were efficient in promoting the cleavage of nucleic acids in the presence of H₂O₂.     

Synthesis,crystal structure,in vitro anticancer and in vivo acute oral toxicity studies of tetramethylene linked bis-benzimidazolium salts and their respective dinuclear Ag(I)–NHC complexes

The proligands of the series tetramethylenebis(N-n-alkylbenzimidazolium bromide) (where n = 3–10) (1–8) as N-heterocyclic carbene (NHC) precursors have been prepared by reacting the initially synthesized N-n-alkyl benzimidazole with 1,4-dibromobutane in 2 : 1 M ratio. A reaction of Ag₂O with 1–8 resulted in the formation of Ag(I) complexes tetramethylenebis{(N-n-alkylylbenzimidazol-2-ylidene)silver(I)hexafluorophosphate} (9–16), respectively. All the synthesized compounds were characterized by FT-IR, ¹H NMR, ¹³C NMR, atomic absorption and elemental analysis. Single-crystal X-ray diffraction study on tetramethylenebis{(N-n-octylbenzimidazol-2-ylidene)silver(I)hexafluorophosphate} (14) has revealed that the complex exists as a dinuclear compound. All compounds were assessed for their antiproliferation test on human colorectal cancer cell line (HCT 116). Interestingly, increasing the n-alkyl chain length from n = 3 to 10 of the proligands and their respective complexes showed trends in increased cytotoxicity against human colon cancer cell line. Cytotoxicity data showed that tetramethylene linked bis-benzimidazolium salts and their respective dinuclear Ag(I)–NHC complexes can be useful therapeutic agents against colon cancer.     

Rhodium(I) and Silver(I) Complexes of 4, 5‐Dicyano‐1, 3‐dimesityl‐ and 4, 5‐Dicyano‐1, 3‐dineopentylimidazol‐2‐ylidene

The new N‐heterocyclic carbene (NHC) precursors 4, ‐dicyano‐1, ‐dimesityl‐ ( 9 ) and 4, 5‐dicyano‐1, 3‐dineopentyl‐2‐(pentafluorophenyl)imidazoline ( 14 ) were synthesized. The structure of 9 could be determined by X‐ray crystallography. With the 2‐pentafluorophenyl‐substituted imidazolines 9 and 14 , the [AgCl(NHC)], [RhCl(COD)(NHC)], and [RhCl(CO)₂(NHC)] complexes [NHC = 4, 5‐dicyano‐1, 3‐dimesitylimidazol‐2‐ylidene ( 3 ) and 4, 5‐dicyano‐1, 3‐dineopentylimidazol‐2‐ylidene ( 4 )] were obtained. Crystal structures of [AgCl( 3 )] ( 15 ), [RhCl(COD)( 3 )] ( 17 ), [RhCl(COD)( 4 )] ( 18 ), and [RhCl(CO)₂( 3 )] ( 19 ) were solved and with the crystal data of 19 , the percent buried volume ( %V_bur) of 31.8(±0.1) % was determined for NHC 3 . Infrared spectra of the imidazolines 9 and 14 and of the complexes 15 – 20 were recorded and the CO stretching frequencies of complexes 19 and 20 were used to determine the Tolman electronic parameters of the newly obtained NHCs 3 (TEP: 2060 cm^–1) and 4 (TEP: 2061 cm^–1), thus proving that 1, 3‐substitution of maleonitrile‐NHCs does not have a significant effect for the high π‐acceptor strength of these carbenes.     

Silver‐Catalyzed Amidiniumation of Alkynes: Isolation of a Silver Intermediate,Synthesis of Enamine Amido Carbene Precursors,and an Unprecedented Umpolung of Propiolamide

A silver‐catalyzed amidiniumation of N‐propiolic formamidines for the synthesis of novel enamine amido carbene precursors is reported. Isolation of a first silver intermediate in silver‐catalyzed amidiniumation of alkynes and other organogold intermediates supports our proposed mechanisms. Several control experiments reveal the unexpected effects of both HOTf and substrate substituents on the choice of either a π or σ,π silver activation mode and the cyclization fashion. Bis(hydroxyimidazol)ium salts were obtained through an unprecedented umpolung of propiolamides. The byproduct Ag₂O as either an oxidant or silver source promotes the syntheses of N‐heterocyclic carbene (NHC) precursors or Ag/NHC complexes.     

Synthesis and antimicrobial activity of bulky 3,5‐di‐tert‐butyl substituent‐containing silver–N‐heterocyclic carbene complexes

A series of novel benzimidazolium bromides containing bulky 3,5‐di‐tert ‐butyl group were synthesized in high yields as N‐heterocyclic carbene (NHC) ligands. These NHC ligands were metallated with Ag₂O under moderate conditions to give novel silver–NHC complexes. The structures of all compounds were characterized using ¹H NMR, ¹³CNMR, infrared and elemental analysis techniques, which supported the proposed structures. The silver–NHC complexes were screened for their in vitro antimicrobial activities against the standard bacterial strains Enterococcus faecalis , Staphylococcus aureus , Escherichia coli and Pseudomonas aeruginosa and the fungal strains Candida albicans and C. tropicalis . The results showed that most of the silver–NHC complexes inhibited the growth of all bacterial strains and fungal strains and were found to display effective antimicrobial activity against different microorganisms.     

Effect of lipophilicity of wingtip groups on the anticancer potential of mono N‐heterocyclic carbene silver(I) complexes: Synthesis,crystal structures and in vitro anticancer study

A series of symmetrically n ‐alkyl‐substituted mono benzimidazolium salts with steady increase in n ‐alkyl chain length have been prepared by stepwise N ‐alkylation resulting in salts ( 1 – 8 ). The mono N‐heterocyclic carbene (NHC)–Ag(I) complexes ( 9 – 16 ) derived from the respective salts were readily accessible by in situ deprotonation using Ag₂O. All the salts and the complexes were characterized using Fourier transform infrared, ¹H NMR, ¹³C NMR and elemental analyses. Furthermore, the structures of salts 3 and 7 and complex 16 were elucidated using X‐ray crystallography, which established that this mono NHC–Ag(I) complex has a linear bis‐carbene arrangement (C₂–Ag). The proligands and the respective Ag(I) complexes were studied for their in vitro anticancer potential against human colon cancer cell line (HCT‐116) using 5‐fluorouracil as a standard. From the IC₅₀ values of all the tested compounds, it can be postulated that there is an influential relationship between the increase in chain length of the wingtip n ‐alkyl groups and the anticancer potential. The proligands 4 – 8 and their respective complexes 12 – 16 with long n ‐alkyl chain lengths (n  = 6–10) showed better IC₅₀ values (0.3–3.9 μM) than the standard drug with the complexes displaying markedly better antiproliferation activity against HCT‐116 cell line than the respective proligands and the standard drug (IC₅₀ = 10.2 μM).     

Dinuclear gold (I)-di-N-heterocyclic carbene complexes: syntheses,structure, density functional theory calculation and photoluminescence study

The synthesis and characterizations for a series of dinuclear gold (I)-di-NHC complexes, 1–8 through the trans-metalation method of their respective silver (I)-di-NHC complexes, i–viii are reported (where NHC = N-heterocyclic carbene). The successful complexation of a series of unusual non-symmetrical and symmetrical di-NHC ligands, 3,3'-(ethane-1,2-diyl)-1-alkylbenzimidazolium-1'-butylbenzimidazolium (with alkyl = methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, benzyl) with the gold (I) ions are suggested by elemental analysis, Fourier transform-infrared, ¹H- and ¹³C-NMR data. The ¹³C-NMR spectra of 1–8 show a singlet sharp peak in the range of 190.00–192.00 ppm, indicating the presence of a carbene carbon that bonded to the gold (I) ion. From single crystal X-ray diffraction data, the structure of complex 6 with the formula of [di-NHC-Au (I)]₂·2PF₆ is obtained [where NHC = 3,3'-(ethane-1,2-diyl)-1-hexylbenzimidazolium-1'-butylbenzimidazolium]. The photophysical study in solid state of 6 displays an intense photoluminescence with a strong emission maxima, λ_em = 480 nm, upon excitation at 340 nm at room temperature. Interestingly, the emission maximum at 77 K shows a structural character with a strong peak at 410 nm, a medium at 433 nm and a weak at 387 nm, accompanied by a tail band to about 500 nm.     

Novel silver(I)N-heterocyclic carbene complexes bearing 2-(4-hydroxyphenyl)ethyl group: Synthesis,characterization, and enzyme inhibition properties

Herein, novel silver-based N-heterocyclic carbene (NHC) complexes bearing 2-(4-hydroxyphenyl)ethyl group were synthesized. Novel Ag(I)NHC complexes were synthesized from the 2-(4-hydroxyphenyl)ethyl-substituted benzimidazolium salts and silver oxide via in situ deprotonation method. The successful formation of all Ag(I)NHC complexes was proved by using ¹H NMR, ¹³C NMR, FTIR spectroscopy, and elemental analysis techniques. In addition, their inhibitory effects have been investigated of these substances on acetylcholinesterase (AChE), α-glycosidase (α-Gly), human carbonic anhydrase I (hCA I), and human carbonic anhydrase II (hCA II) enzymes. It has been seen that all compounds have a better ability to inhibit compared with existing tried inhibitors. Among these, the best inhibitor against AChE enzyme is 1g (K_i : 9.54 ± 0.98 μM and IC₅₀ : 17.40), and against α-Gly, 1c showed the highest effect (K_i 3.09 ± 0.36 μM and IC₅₀ 7.91). The best inhibitor against hCA I and hCA II enzymes are 1c and 1g compounds. For hCA I and hCA II, IC₅₀ values were calculated as 17.85 and 9.06 μM and K_i values were measured as 5.45 ± 2.02 and 8.99 ± 2.02 μM, respectively.     

Palladium(II)‐N‐heterocyclic carbene complexes: synthesis,characterization and catalytic application

N‐Heterocyclic carbenes (NHCs) are of great importance and are powerful ligands for transition metals. A new series of sterically hindered benzimidazole‐based NHC ligands (LHX) ( 2a , 2b , 2c , 2d , 2e , 2f ), silver–NHC complexes ( 3a , 3b , 3c , 3d , 3e , 3f ) and palladium–NHC complexes ( 4a , 4b , 4c , 4d , 4e , 4f ) have been synthesized and characterized using appropriate spectroscopic techniques. Studies have focused on the development of a more efficient catalytic system for the Suzuki coupling reaction of aryl chlorides. Catalytic performance of Pd–NHC complexes and in situ prepared Pd(OAc)₂/LHX catalysts has been investigated for the Suzuki cross‐coupling reaction under mild reaction conditions in aqueous N,N‐dimethylformamide (DMF). These complexes smoothly catalyzed the Suzuki–Miyaura reactions of electron‐rich and electron‐poor aryl chlorides. Copyright © 2014 John Wiley & Sons, Ltd.     

Silver‐Catalyzed Amidiniumation of Alkynes: Isolation of a Silver Intermediate,Synthesis of Enamine Amido Carbene Precursors,and an Unprecedented Umpolung of Propiolamide

A silver‐catalyzed amidiniumation of N‐propiolic formamidines for the synthesis of novel enamine amido carbene precursors is reported. Isolation of a first silver intermediate in silver‐catalyzed amidiniumation of alkynes and other organogold intermediates supports our proposed mechanisms. Several control experiments reveal the unexpected effects of both HOTf and substrate substituents on the choice of either a π or σ,π silver activation mode and the cyclization fashion. Bis(hydroxyimidazol)ium salts were obtained through an unprecedented umpolung of propiolamides. The byproduct Ag₂O as either an oxidant or silver source promotes the syntheses of N‐heterocyclic carbene (NHC) precursors or Ag/NHC complexes.