Insights into the photoactivatable CO releasing properties of dicarbonyl Ru(II) complex with 8-amino quinoline ligand: Experimental and theoretical studies.

Reaction between the polymeric [RuCl2(CO)2]n and the N,N-bidentate ligand, 8-amino-quinoline (Quin), in methanol, afforded the photoactivated CO releasing molecule with the formula of trans-(Cl,Cl)-[RuCl2(CO)2Quin]. In the presence of biomolecules or in solvents with varying polarity and coordinating abilities, the solvatochromic characteristics and dark stability were investigated. A new board band emerged in the visible spectrum during the illumination, and its position varies according to the type of solvent used, indicating the role of the solvent in controlling the nature of the CO-depleted species. Spectral methods were used in combination with density functional theory simulations to get insight into the local minimum structure and the electronic properties of the Ru(II) complex. The results of the myoglobin assay showed that within the first two hours of illumination, one of the two CO molecules was released. The cytotoxic properties of the Ru(II)-based complex were investigated against normal mice bone marrow stromal cells and malignant human acute monocytic leukaemia cells.

Metal-based carbon monoxide releasing molecules with promising cytotoxic properties.

Carbon monoxide, the "silent killer" gas, is increasingly recognised as an important signalling molecule in human physiology, which has beneficial biological properties. A particular way of achieving controlled CO administration is based on the use of biocompatible molecules that only release CO when triggered by internal or external factors. These approaches include the development of pharmacologically effective prodrugs known as CO releasing molecules (CORMs), which can supply biological systems with CO in well-regulated doses. An overview of transition metal-based CORMs with cytotoxic properties is here reported. The mechanisms at the basis of the biological activities of these molecules and their potential therapeutical applications with respect to their stability and CO releasing properties have been discussed. The activation of metal-based CORMs is determined by the type of metal and by the nature and features of the auxiliary ligands, which affect the metal core electronic density and therefore the prodrug resistance towards oxidation and CO release ability. A major role in regulating the cytotoxic properties of these CORMs is played by CO and/or CO-depleted species. However, several mysteries concerning the cytotoxicity of CORMs remain as intriguing questions for scientists.

Antimicrobial properties of triazolato terpyridine Pd(II) and Pt(II) complexes formed by [3+2] cycloaddition coupling reaction.

Modern classes of antimicrobials are crucial because most drugs in development today are basically antibiotic derivatives. Even though a large number of metal-based compounds have been studied as antimicrobial agents, relatively few studies have examined the antimicrobial properties of Pd(II) and Pt(II) compounds. The [3+2] cycloaddition reactions of [M(N3)L]PF6 (M = Pd(II) and Pt(II); L = 4'-(2-pyridyl)-2,2':6',2″-terpyridine) with 4,4,4-trifluoro-2-butynoic acid ethyl ester gave the corresponding triazolate complexes. The reaction products were fully characterized with a variety of analytical and spectroscopic tools including X-ray crystallographic analysis. The crystal structure of [Pd(triazolatoCF3,COOCH2CH3)L]PF6 provided cut-off evidence that the kinetically formed N1-triazolato isomer favoured the isomerization to the thermodynamically stable N2-analogue. The experimental work was complemented with computational work to get an insight into the nature of the predominant triazolate isomer. The lysozyme binding affinity of the triazolate complexes was examined by mass spectrometry. An analysis of the lysozyme Pd(II) adducts suggests a coordinative covalent mode of binding via the loss of the triazolato ligand. The free ligand and its triazolate complexes displayed selective toxicity against Candida albicans and Cryptococcus neoformans, while no cytotoxicity was observed against the normal human embryonic kidney cell line.

Palladium(II) Complexes of 4-Phenyl-3-thiosemicarbazone Ligands: Insights Into Cytotoxic Properties and Mode of Cell Death.

Reactions between sodium tetrachloropalladate and 2- (or 4-) substituted 4-phenyl-3-thiosemicarbazone ligands (HLR), with various electron-donating and electron-withdrawing substituents (R = OCH3, NO2, and Cl), afford square-planar complexes of the general formula [Pd(LR)2]. Ground-state geometry optimization and the vibrational analysis of cis- and trans-isomers of the complexes were carried out to get an insight into the stereochemistry of the complexes. Natural bond orbital analysis was used to analyze how the nature of the substituent affects the natural charge of the metal center, the type of hybridization, and the strength of the M-N and M-S bonds. Using spectrophotometry, the stability of the complexes, and their DNA binding abilities were assessed. The Pd(II) complexes showed moderate cytotoxicity against MCF-7 and Caco-2 cell lines, two of the assessed malignant cell lines, resulting in all known cell death types, including early apoptotic bodies and late apoptotic vacuoles as well as evident necrotic bodies.

Role of the auxiliary ligand in determining the genotoxicity and mode of cell death of thiosemicarbazone Pd(II) complexes.

A series of Pd(II) complexes of the general formula [PdX(NNS)] (X = Cl, Br, I, NCS and phenyl-tetrazole-thiolato; NNS = 2-quinolinecarboxyaldehyde-N4-phenylthiosemicarbazone) was tested against four malignant cell lines for their antiproliferative properties and the outcomes were compared to those seen in normal mouse splenocytes. Various auxiliary ligands were substituted in order to investigate the impact of the character of the ligand on the cytotoxicity of this class of Pd(II) complexes. The iodo complex was the most cytotoxic compound towards the Caco-2 cell line in this study. The improved apoptosis and necrosis cell modes were in accordance with the fragmentation results of DNA, which revealed increased fragmentation terminals, especially in isothiocyanate and tetrazole-thiolato complexes. After 24 hours, at half the IC50 of each complex, the complex-treated cells exhibited considerable genotoxicity when compared to the corresponding non-treated control especially in the case of isothiocyanate and tetrazole-thiolato complexes.

Reactivity of azido terpyridine Pd(ii) and Pt(ii) complexes towards 4,4,4-trifluoro-2-butynoic acid: structural insight into the triazolato coordination mode.

The mono- and binuclear azido terpyridine square-planar complexes of ionic formulas, [Pd2(N3)2L]2+ and [Pt(N3)L]+ (L = 1,4-bis(2,2':6',2''-terpyridin-4'yl)benzene), underwent the catalyst-free [3 + 2] cycloaddition coupling with 4,4,4-trifluoro-2-butynoic acid at ambient temperature affording the corresponding triazolate complexes. A mixture of triazolate isomers was generated by these inorganic click reactions. An increase in the solubility of the compounds was achieved by replacing the azido ligand with a triazolato ligand. By calculating the vibrational modes and comparing the total electronic and zero-point energy values, the local minimum structures of the complexes and the nature of the predominant triazolate isomer were verified. The theoretical work was complemented with natural bond analysis to get an insight into the natural charge and electronic arrangement of the metal ion, the hybridization of M-L bonds and strength of M-N bonds.

In vitro cytotoxicity of Mn(I) and Ru(II) carbonyls with a diphenyl pyridyl phosphine coligand towards leukaemia.

Human acute monocytic leukaemia cells were tested under both dark and light conditions for their susceptibility to Mn(I) and Ru(II) carbonyl complexes with a diphenyl pyridyl phosphine coligand. The Ru(II) complex (IC50 = 7.13 ± 0.8 µM) displayed higher outstanding potency against leukaemia than the Mn(I) analogue (54.58 ± 4.1 µM) in the dark and both complexes were completely harmless to healthy mouse bone marrow cells.

Solar-driven seawater desalination via plasmonic hybrid MOF/polymer and its antibacterial activity.

In recent years, solar seawater desalination has been considered to be a promising and cost-effective technique to produce clean sources for water treatment and water deficiency. In addition, this technique shows high photothermal conversion efficiency by solar collectors to transfer solar energy into heat and the transformation of molecules in the capillaries of solar evaporators. In this study, we report the preparation of graphene-supported MIL-125 with polyurethane foam (MGPU) for solar steam generation. We modified MGPU by using the plasmonic nanoparticles of Ag and a polymer of polyaniline to increase the evaporation rate. Polyurethane foam can float on the surface of water and self-pump water by its hydrophilic porous structure, superior thermal insulation capabilities, and easy fabrication. MIL-125 has a high salt rejection and higher water permeability. It can reduce the affinity between water molecules and the pore surface of membrane, making it simple for water molecules to move through the pores. GO is a great alternative for steam generation applications since it exhibits broad-band light. The strong solar absorption, photothermal conversion efficiency, and photoreaction efficiency are enhanced by the use of silver nanoparticles in the photoreaction. The salt resistance capability is enhanced in saline water in the presence of polyaniline in a composite. Under one solar irradiation, the Ag/PANI/GO@MIL-125 (Ag-PMG) nanocomposite demonstrates an average 1.26 kg m2 h-1 rate of evaporation and an efficiency as high as 90%. The composite exhibits remarkable stability and durability after more than 10 cycles of use without a noticeable decrease in activity. In addition, the composite exhibits excellent organic dye removal from contaminated water and generates pure condensed freshwater. The antibacterial photoactivity of the photocatalysts was examined against B. subtilis and E. coli. The results demonstrate that Ag-PMG shows higher antibacterial activity than MIL-125 and PMG. It was shown that the presence of rGO, PANI, and Ag in the sample enhances the antimicrobial activity.

Sulfonate improves water solubility and cell selective toxicity and alters the lysozyme binding activity of half sandwich Rh(iii) complexes.

Introduction of the propyl-sulfonic acid group at N1 of the coordinated 2-(2-pyridyl)benzimidazole ligand (L) in [RhCl(η5-C5Me5)L](CF3SO3) gives rise to a water-soluble complex, which can bind to the model protein lysozyme via non-covalent interactions. The complex shows selective moderate toxicity against Cryptococcus neoformans (MIC = 21.6-43.3 µM) and exhibits no cytotoxicity to healthy HEK293 cells.

Role of the ancillary ligand in controlling the lysozyme affinity and electronic properties of terpyridine fac-Re(CO)3 complexes.

The lysozyme binding affinity and the electronic properties of [ReX(CO)3(terpy-κ2N1,N2)] (X = Br- and triazolateCOOCH2CH3,CF3) were reported. The triazolate complex was prepared in a [3 + 2] cycloaddition click reaction. The bromo compound reacted with lysozyme affording adducts with Re(CO)3+ fragments, while the triazolate compound persisted. A red shift of the MLCT band of the triazolate compound in progressively less polar solvents may be due to the negative solvatochromism.

Spectroscopic investigation of π-acceptors in the determination and photoinduced degradation of Sulfacetamide.

The presence of expired and unused Sulfacetamide (SA) drug in water led to a global need for the development of effective advanced method for the quantitative analysis and for minimizing its occurrence in the nature. To find new effective photochemical decomposition method close to that obtained by the well-known Fenton reaction, the photodegradation of SA was investigated in presence of dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and/or other common additives at two different wavelengths (365 and 256 nm). The role of DDQ in the degradation process of SA was evaluated in comparison to the other investigated π-acceptor systems (Chloranilic acid (CHL) and Picric acid (PA)). While the photodegradation process of SA was hardly to proceed in the absence of a catalyst and/or additive, addition of DDQ and NaNO2 to the solution of SA induced decomposition of about 94% of SA within 25 min upon the exposure to light source at 256 nm. On the other hand, SA was quantitatively analyzed by recording the absorbance of its charge transfer (CT) products with DDQ, CHL and PA at a certain wavelength. CHL is preferred with concentrated samples of SA, while PA is recommended for diluted samples of SA. SA â†’ DDQ has a widely range of stability over the pH range of 4.5-12.0. While SA â†’ CHL is stable only in the acidic medium (pH = 4.8-5.6), SA â†’ PA is steady in the basic medium (pH = 7.5-11.0). The nature of the DDQ CT complex was investigated in the solid state. The electronic structures of the complexes were studied by calculating the time dependent density functional theory (TDDFT) spectra.

Lysozyme and DNA binding affinity of Pd(ii) and Pt(ii) complexes bearing charged N,N-pyridylbenzimidazole bidentate ligands.

New cisplatin analogue Pd(ii) and Pt(ii) complexes bearing charged pyridylbenzimidazole derivatives furnished with either an alkylated sulfonate or a phosphonium side chain were synthesized, fully characterized and tested for their antimicrobial and cytotoxic activities against noncancerous human embryonic kidney cells (HEK293). The interactions with CT-DNA were investigated using UV/vis spectroscopy. Assignment of the electronic transitions was performed with the aid of TDDFT. The complexes showed interesting antifungal activity against Candida albicans and Cryptococcus neoformans. The Pd(ii) complex conjugated with alkylated triphenylphosphonium exhibited higher cytotoxicity (CC50 = 8.932 µg mL-1, equivalent to 12 nM) than the others. The reactivity towards hen egg white lysozyme (HEWL) was investigated by electrospray ionization mass spectrometry. The formation of DNA- and HEWL-adducts was achieved via the noncovalent and covalent interactions.

Trapping of muscle relaxant methocarbamol degradation product by complexation with copper(II) ion: spectroscopic and quantum chemical studies.

Structural properties of methocarbamol (Mcm) were extensively studied both experimentally and theoretically using FT IR, (1)H NMR, UV-Vis., geometry optimization, Mulliken charge, and molecular electrostatic potential. Stability arises from hyper-conjugative interactions, charge delocalization and H-bonding was analyzed using natural bond orbital (NBO) analysis. Mcm was decomposed in ethanol/water mixture at 80°C to guaifenesin [(RS)-3-(2-methoxyphenoxy)propane-1,2-diol] and carbamate ion [NH2COO(-)], where the degradation mechanism was explained by trapping the carbamate ion via the complexation with copper(II) ion. The structure of the isolated complex ([Cu(NH2COO)2(H2O)]⋅4H2O) was elucidated by spectral, thermal, and magnetic tools. Electronic spectra were discussed by TD-DFT and the descriptions of frontier molecular orbitals and the relocations of the electron density were determined. Calculated g-tensor values showed best agreement with experimental values from EPR when carried out using both the B3LYP and B3PW91 functional.

New thiocyanate potentiometric sensors based on sulfadimidine metal complexes: experimental and theoretical studies.

Three sulfadimidine metal complexes (M=Fe(III), Cu(II), and Ag(I)) were prepared, characterized, and examined as neutral carriers for the determination of SCN(-) using modified carbon paste electrode. These sensors were successfully applied in the pure samples, and biological fluids. The electrode mechanism was investigated by UV-vis and FT IR. The experimental studies were complemented by quantum chemical calculations at DFT/B3LYP level of theory. The best performance was observed for Cu(II) electrode (C) containing 7.0% complex, 53.0% o-nitrophenyloctyl ether, 37.0% graphite and 3.0% cetylpyridinium chloride, and also for Fe(III)-electrode (A) having 6.0% complex, 52.0% o-nitro phenyloctyl ether, 40.5% graphite and 2.5% cetylpyridinium chloride.

N-acetyltransferase 2, cytochrome P4502E1 and glutathione S-transferase genotypes in antitubercular treatment-induced hepatotoxicity in North Indians.

WHAT IS KNOWN AND OBJECTIVE: Tuberculosis (TB) is a major cause of illness and death in developing countries. Hepatotoxicity is a serious side effect of antituberculosis treatment (ATT). NAT2, CYP2E1 and glutathione S-transferase (GST) gene polymorphisms may play an important role in ATT-induced hepatotoxicity. So, elucidating the genetics involved in anti-TB drug-induced hepatotoxicity in patients would be of utmost clinical significance. Therefore, the objective of the study was to elucidate the role of NAT2, CYP2E1 and GST gene polymorphisms in ATT-induced hepatotoxicity in North Indian patients. METHODS: Three hundred patients with pulmonary and extra-pulmonary TB were enrolled. Total genomic DNA was isolated from each patient's peripheral lymphocytes using phenol-chloroform method, and genetic polymorphic analysis for N-acetyltransferase 2 (NAT2), cytochrome P4502E1 (CYP2E1) and GST was performed by polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP). RESULTS AND DISCUSSION: Of the 300 patients, 185 were males and 115 females. Among them, 33 males and 22 females developed ATT-induced hepatotoxicity. There were significant increases in alanine aminotransferase, aspartate aminotransferase and bilirubin levels in patients with ATT-induced hepatotoxicity at 1 month of treatment. NAT2 5/7 and 6/7 were significantly higher in hepatotoxicity patients as compared to the non-hepatotoxicity group. c1/c1 allele of CYP2E1 gene was lower (50·9%) in ATT-induced hepatotoxicity patients as compared to non-hepatotoxicity patients (61·2%), whereas c1/c2 and c2/c2 alleles were higher, but not statistically significant. GSTM1 was significantly higher in hepatotoxicity patients as compared to non-hepatotoxicity patients, whereas GSTT1 and GSTT1/M1 were lower, but not statistically significant. WHAT IS NEW AND CONCLUSION: This study indicates that patients with slow-acetylator genotypes (NAT2 5/7, 6/7) and GSTM1 allele of GST enzyme were at higher risk of ATT-induced hepatotoxicity.

Antioxidant status and GST gene polymorphisms in antitubercular treatment-induced hepatotoxicity patients.

INTRODUCTION: Hepatotoxicity is a serious adverse effect of antituberculosis treatment (ATT). Glutathione S-transferase (GST) is involved in the detoxification of toxic metabolites produced as a result of ATT, increased oxidative stress and decreased antioxidant levels, and differences in the GST polymorphism may be one of the causes of ATT-induced hepatotoxicity. AIM: This study was undertaken to study the relationship among antioxidant status, oxidative stress and GST gene polymorphisms in the development of ATT-induced hepatotoxicity in Indian patients. METHODOLOGY: Two hundred fifty TB patients attending clinics in the Gastroenterology and Thoracic Department, PGIMER, Chandigarh, were enrolled. Liver marker enzymes, markers of oxidative stress, levels of antioxidants and identification of GSTT1, GSTM1 and GSTP polymorphisms were performed using standard protocols. RESULTS: Of the 250 patients, 160 were males. Of the 160 males, 18 (11.3 %) had ATT-induced hepatotoxicity and 142 no hepatotoxicity, while of 90 females, 12 (13.3 %) had hepatotoxicity and 78 no hepatotoxicity. Patients who developed ATT-induced hepatotoxicity had significantly higher oxidative stress compared to those who did not develop hepatotoxicity at between 1 and 2 months of treatment. Among antioxidants, catalase did not show any significant difference at 2 and 4 months of treatment. The presence of GSTM1 was higher in hepatotoxicity patients as compared to non-hepatotoxicity patients, while GSTT1 and GST1/M1 were lower. CONCLUSION: Therefore, in this study, the possible association of oxidative stress with ATT-induced hepatotoxicity was observed. A role of the GST polymorphism in ATT-induced hepatotoxicity was also found and thus could possibly identify the groups at highest risk of developing ATT-induced hepatotoxicity.

Comparison between acetylator phenotype and genotype polymorphism of n-acetyltransferase-2 in tuberculosis patients.

BACKGROUND: Isoniazid (INH) is one of the most important drugs of antitubercular treatment regime, and in some cases it causes hepatotoxicity. It is metabolized by hepatic N-acetyltransferase-2 (NAT2). AIM: To compare whether both methods, i.e., genotype NAT2 and phenotype test of measuring serum INH levels, are useful to identify acetylator status of patients on antitubercular treatment (ATT). METHODS: A total of 251 tuberculosis (TB) patients on standard treatment were followed up to 6 months for this study. NAT2 genotype was assessed by PCR with restriction fragment length polymorphism (RFLP) whereas serum INH levels were measured by fluorometry. RESULTS: Of the 251 patients, 50 (19.9%) developed ATT-induced hepatotoxicity. By phenotypic estimation, in the hepatotoxicity group, 17/50 (34%) were slow acetylators whereas 33/50 (66%) were fast acetylators. Genotypically, 19/50 (38%) were slow acetylators and 31/50 (62%) fast acetylators. By phenotypic analysis, in non-hepatotoxicity group, 46/201 (22.9%) were slow acetylators and 155/201 (77.1%) fast acetylators. By genotypic analysis, 30/201 (14.9%) were slow acetylators and 171/201 (85%) fast acetylators. Overall, slow acetylators (25.1%) measured phenotypically were not significantly different from slow acetylators (19.5%) measured genotypically. CONCLUSION: This study suggests that the acetylator status of TB patients can be detected by phenotypic method as efficaciously as by genotypic method. Therefore, phenotypic method can replace genotypic method to determine acetylating status as phenotypic method is simple and inexpensive.

Garlic in health and disease.

The present article reviews the historical and popular uses of garlic, its antioxidant, haematological, antimicrobial, hepatoprotective and antineoplastic properties and its potential toxicity (from sulfoxide). Garlic has been suggested to affect several cardiovascular risk factors. It has also been shown that garlic and its organic allyl sulfur components are effective inhibitors of the cancer process. Since garlic and its constituents can suppress carcinogen formation, bioactivation and tumour proliferation, it is imperative that biomarkers be established to identify which individuals might benefit most. Garlic powder, aged garlic and garlic oil have demonstrated antiplatelet and anticoagulant effects by interfering with cyclo-oxygenase-mediated thromboxane synthesis. Garlic has also been found to have synergistic effects against Helicobacter pylori with a proton pump inhibitor. The active compound allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages. Freshly prepared garlic homogenate protects against isoniazid+rifampicin-induced liver injury in experimental animal models. Several mechanisms are likely to account for this protection.

Hepatoprotection by carotenoids in isoniazid-rifampicin induced hepatic injury in rats.

This study evaluates the hepatoprotective effect of carotenoids against isoniazid (INH) and rifampicin (RIF). Thirty-six adult rats were divided into the following 4 groups: (1) control group treated with normal saline; (2) INH + RIF group treated with 50 mg·(kg body mass)-1·day-1 of INH and RIF each; (3) INH + RIF+ carotenoids group treated with 50 mg·(kg body mass)-1·day-1 of INH and RIF each and 10 mg·(kg body mass)-1·day-1 of carotenoids; and (4) carotenoids group treated with 10 mg·(kg body mass)-1·day-1 of carotenoids for 28 days intragastrically. Oxidative stress and antioxidant levels in liver and blood, liver histology and change in transaminases were measured in all the above-mentioned groups. There was an increase in lipid peroxidation with a reduction in thiols, catalase, and superoxide dismutase (SOD) in the liver and blood of rats accompanied by an increase in transaminases, bilirubin, and alkaline phosphatase. Treatment with carotenoids along with INH + RIF partially reversed lipid peroxidation, thiols, catalase, and SOD in the liver and blood of rats. Elevated levels of the enzymes in serum were also reversed partially by this treatment. The degree of necrosis, portal triaditis, and inflammation were also lowered in the carotenoids group. In conclusion, carotenoids supplementation in INH + RIF treated rats showed partial protection.

New selenite ion-selective electrodes based on 5,10,15,20-tetrakis-(4-methoxyphenyl)-21H,23H-porphyrin-Co(II).

New polymeric membrane (PME), modified carbon paste (MCPE), and coated wire (CWE) selenite ion-selective electrodes based on 5,10,15,20-tetrakis-(4-methoxyphenyl)-21H,23H-porphyrin-Co(II) (CoTMeOPP) are reported. The best composition was the electrode containing 2% CoTMeOPP as the active material and 49% TCP as plasticizer. The electrodes reveal a Nernstian behavior over a concentration range of 5.5x10(-5) to 1.1x10(-2) M for PME, 5.2x10(-5) to 1.2x10(-2) M for MCPE and 1.2x10(-4) to 4.4x10(-3) M for CWE. The potentiometric response is pH dependent, since selenous acid is a diprotic acid. The slope of the selenite PVC electrode was -57.0 mV for the monovalent anion at pH 6.47, and -26.0 mV for the divalent anion at pH 11.00. The detection limits were 3.4x10(-5) and 4.7x10(-5) M at pH values 6.47 and 11.00, respectively. The electrodes manifest advantages of low resistance, very short response time (15 s), and most importantly good selectivities relative to a wide variety of other anions. In fact, the proposed selenite ion-selective electrodes show a great improvement compared to previously reported electrodes for selenite ion. The electrode was used for the determination of selenite in selenite/selenate mixture, in sodium selenite raw material powder, and in VitaFit Selenium ACE antioxidant tablets with recovery ranges of 90.0-103.3%.