Thermally induced solid-state transformation of cimetidine. A multi-spectroscopic/chemometrics determination of the kinetics of the process and structural elucidation of one of the products as a stable N3-enamino tautomer

Exposure of cimetidine (CIM) to dry heat (160–180 °C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics.     

Organometallic complexes with biological molecues,part 3. in vivo cytotoxicity of diorganotin (IV) chloro and triorganotin (IV) chloro derivatives of penicillin g on chromosomes of aphanius fasciatus (pisces,cyprinodontiformes)

In order to obtain a continuous source of mitotic metaphases, gill tissue of Aphaius fasciatus (Pisces, Cyprinodontiformes) has been successfully employed. Results gathered after exposure of fish to R₂SnClpenG, R₃SnClpenGNa, to the parents R₂SnCl₂, R₃SnCl and to penGNa (penGNa = penicillinGNa; R = methyl, butyl and phenyl) suggest that both the parent organotin (IV) chloride and organotin (IV) chloropenG derivatives are toxic while penGNa exerts no significant toxic activity. Essentially, all of the chromosome abnormalities are classifiable as irregularly staining of chromosomes, breakages, side-arm bridges or pseudochiasmata.     

Penetration and interactions of the antimicrobial peptide, microcin J25, into uncharged phospholipid monolayers

Microcin J25 forms stable monolayers at the air-water interface showing a collapse at a surface pressure of 5 mN/m, 220 mV of surface potential, and 6 fV per squared centimeter of surface potential per unit of molecular surface density. The adsorption of microcin J25 from the subphase at clean interfaces leads to a rise of 10 mN/m in surface pressure and a surface potential of 220 mV. From these data microcin appears to be a poor surfactant per se. Nevertheless, the interaction with the lipid monolayer further increase the stability of the peptide at the interface depending on the mode in which the monolayer is formed. Spreading with egg PC leads to nonideal mixing up to 7 mN/m, with hyperpolarization and expansion of components at the interface, with a small excess free energy of mixing caused by favorable contributions to entropy due to molecular area expansion compensating for the unfavorable enthalpy changes arising from repulsive dipolar interactions. Above 7 mN/m microcin is squeezed out, leaving a film of pure phospholipid. Nevertheless, the presence of lipid at 10 and 20 mN/m stabilize further microcin at the interface and adsorption from the subphase proceeds up to 30 mN/m, equivalent to surface pressure in bilayers.     

Application of a chemometric method for simultaneous determination of acetaminophen and diclofenac in content-uniformity and drug-dissolution studies

A new, repeatable, and rapid method has been developed for resolution of binary mixtures of acetaminophen and diclofenac with minimum sample pretreatment and without separation of the analytes. The method, based on the PLS1 processing of absorbance data in the UV region, was successfully used for quantification of the drug content of three tablet preparations. The results obtained were in good agreement with HPLC recovery data. The method also enabled determination of drug-dissolution profiles of these commercial tablets, by simultaneous determination of both analytes during the dissolution test.     

Direct Chromatographic Resolution of P-Chiral Organophosphorus Compounds at Analytical and Preparative Levels

Abstract

High-performance liquid chromatography utilizing chiral stationary phases (CSPs) is well established as a very simple and efficient method for obtaining discrete amounts of optically active compounds with high e.e., as well as for determining their enantiomeric composition We wish to demonstrate in the present work that a totally synthetic brush-type π-acidic CSP based on a bis(N,N′-3,5-dinitrobenzoyl) derivative of (R,R)- or (S,S)-trans-1,2-diaminocyclohexane as selector can be used successfully to resolve variety of chiral organophosphorus compounds containing stereogenic centers at phosphorus     

Os(VIII)-catalysed oxidation of sulfides by sodium salt of N-chlorobenzenesulfonamide

Catalytic activity of Os(VIII) in the oxidation of some twenty organic sulfides with sodium salt of N-chlorobenzenesulfonamide (CAB) has been investigated in alkaline (pH8.7) t-butanol–water (1:1 v/v) medium. Significant retarding influence of [OH⁻] on the reactivity is exhibited. The catalysed reaction is strongly accelerated in the presence of Hg(II). Imperfections are observed in the linear Hammett relationship in the case of –NO₂ substituents.     

Formation of a tricyclic nucleoside from deoxyguanosine via an O6-N1-transposition

The synthesis of a tricyclic deoxynucleoside by reaction of β-substituted ethanols with an activated deoxyguanosine is described. Its formation is rationnalised by an O⁶-N¹-transposition.     

Raman spectroscopic investigation on the microenvironment of the liver tissues of Zebrafish (Danio rerio) due to titanium dioxide exposure

Nano titanium dioxide (nTiO₂), generally considered to be toxicologically inert, is manufactured in large quantities and extensively applied in consumer products. The small size and large surface area endow them with an active group or intrinsic toxicity. Advances in instrumentation are making Raman spectroscopy the tool of choice for an increasing number of (bio) chemical applications. One of the great advantages of this technique is its ability to provide information on the concentration, structure and interaction of biochemical molecules in their microenvironments within intact cells and tissues, non-destructively. Zebrafish (Danio rerio), one of the most important vertebrate model organisms used in developmental biology, are increasingly used in biomedical research, particularly as a model of human disease. In the present work, an attempt is made to study the effect of titanium dioxide, both nano and bulk, on the microenvironment of the liver tissues of Zebrafish using FT-Raman spectroscopy. The results of the present study suggest that TiO₂ exposure demonstrate a marked influence on the microenvironments of the liver tissues of Zebrafish. A shift to a higher wavenumber and an increase in the intensity of the band at ∼1087 cm⁻¹ in the TiO₂ exposed tissues suggest that some of the conformational changes resulting from the alkali recovery process takes place due to TiO₂ exposure. The decreased intensity ratio (I₃₂₂₀/I₃₄₀₀) observed in the titanium-exposed tissues suggests a decreased water domain size, which could be interpreted in terms of weaker hydrogen-bonded molecular species of water in the TiO₂ exposed tissues. The observed shift of COO⁻ bands to higher frequencies shows the disruption of salt bridges as a result of a change in the oppositely charged partners and due to the enhanced random coil conformation. The variation in the intensity ratio of the tyrosyl doublet (I₈₅₈/I₈₂₅) indicates variation in the hydrogen bonding of the phenolic hydroxyl group due to TiO₂ exposure. The results further suggest that the microenvironments are greatly altered due to titanium nano exposure when compared to titanium bulk. In conclusion, the results indicate that FT-Raman spectroscopy might be a useful tool for rapid assessment of nano particle biological interactions.     

A multivariate approach for the simultaneous determination of losartan potassium and hydrochlorothiazide in a combined pharmaceutical tablet formulation

A convenient new method for the simultaneous determination of losartan potassium and hydrochlorothiazide, with minimum sample pretreatment, is described. The procedure, based on the multivariate analysis of spectral data in the 220−274 nm region by the partial least squares algorithm, is linear in the concentration range 1.06−5.70 mg L⁻¹ for hydrochlorothiazide and 4.0−22.2 mg L⁻¹ for losartan. It is simple, rapid and robust, allowing accurate and precise results, with drug recovery rates of 99.3 and 100.4% and relative standard deviations of 1.7 and 1.0% obtained for hydrochlorothiazide and losartan, respectively. The method was applied to the simultaneous determination of both analytes in tablets, and it provided good results which were in statistical agreement with those provided by independent HPLC analyses of the samples. The method has also been successfully applied for the construction of drug dissolution profiles of a commercial pharmaceutical preparation containing both analytes. Figure A UV-PLS method for the simultaneous determination of losartan potassium and hydrochlorothiazide in pharmaceutical tablet formulations has been developed and validated