Kinetics and mechanism of oxidation of <Emphasis Type="SmallCaps">l</Emphasis>-cystine by manganese(III) in sulfuric acid medium

The kinetics of oxidation of l-cystine by Mn^III have been studied in sulfuric acid medium at 30 °C. The reaction was followed spectrophotometrically at λmax = 500 nm. The reaction shows first order dependence on both [Mn^III] and [cystine]. It was found that the rate of the reaction decreases with increase of [H⁺] up to a certain point and then remains unchanged. The oxidation product of the reaction was found to be cysteic acid. A plausible mechanism has been proposed to account for the experimental results.     

Synthesis of potential impurities of cloxacillin sodium drug substance

The present work describes the synthesis and characterization of six related compounds of cloxacillin sodium ( 1 ) viz penicilloic acid of cloxacillin (2) , (3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl) glycine (Glycine analogue of cloxacillin) (3), CMICAA adduct of cloxacillin (4) , (4S)-2-(carboxy(3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamido) methyl)-3-(2-ethylhexanoyl)-5,5-dimethylthiazolidine-4-carboxylic acid (N-2-ethylhexanoyl penicilloic acid of cloxacillin) ( 5 ), N-Acetylated penicilloic acid of cloxacillin ( 6 ), and Cloxacillin Penicillamide (7) . These related compounds are very essential in the process development of cloxacillin sodium and are used as reference standards to determine the quality of the drug substance.     

Inhibitor mediated protein degradation

The discovery of drugs that cause the degradation of their target proteins has been largely serendipitous. Here we report that the tert-butyl carbamate-protected arginine (Boc(3)Arg) moiety provides a general strategy for the design of degradation-inducing inhibitors. The covalent inactivators ethacrynic acid and thiobenzofurazan cause the specific degradation of glutathione-S-transferase when linked to Boc(3)Arg. Similarly, the degradation of dihydrofolate reductase is induced when cells are treated with the noncovalent inhibitor trimethoprim linked to Boc(3)Arg. Degradation is rapid and robust, with 30%-80% of these abundant target proteins consumed within 1.3-5 hr. The proteasome is required for Boc(3)Arg-mediated degradation, but ATP is not necessary and the ubiquitin pathways do not appear to be involved. These results suggest that the Boc(3)Arg moiety may provide a general strategy to construct inhibitors that induce targeted protein degradation.     

Prospects of second generation artificial intelligence tools in calibration of chemical sensors

Multivariate data driven calibration models with neural networks (NNs) are developed for binary (Cu++ and Ca++) and quaternary (K+, Ca++, NO3- and Cl-) ion-selective electrode (ISE) data. The response profiles of ISEs with concentrations are non-linear and sub-Nernstian. This task represents function approximation of multi-variate, multi-response, correlated, non-linear data with unknown noise structure i.e. multi-component calibration/prediction in chemometric parlance. Radial distribution function (RBF) and Fuzzy-ARTMAP-NN models implemented in the software packages, TRAJAN and Professional II, are employed for the calibration. The optimum NN models reported are based on residuals in concentration space. Being a data driven information technology, NN does not require a model, prior- or posterior- distribution of data or noise structure. Missing information, spikes or newer trends in different concentration ranges can be modeled through novelty detection. Two simulated data sets generated from mathematical functions are modeled as a function of number of data points and network parameters like number of neurons and nearest neighbors. The success of RBF and Fuzzy-ARTMAP-NNs to develop adequate calibration models for experimental data and function approximation models for more complex simulated data sets ensures AI2 (artificial intelligence, 2nd generation) as a promising technology in quantitation.     

Envirometrics. Part I: Modeling of water salinity and air quality data

Envirometrics utilises advanced mathematical, statistical and information tools to extract information. Two typical environmental data sets are analysed using MVATOB (Multi Variate Analysis TOol Box). The first data set corresponds to the variable river salinity. Least median squares (LMS) detected the outliers whereas linear least squares (LLS) could not detect and remove the outliers. The second data set consists of daily readings of air quality values. Outliers are detected by LMS and unbiased regression coefficients are estimated by multi-linear regression (MLR). As explanatory variables are not independent, principal component regression (PCR) and partial least squares regression (PLSR) are used. Both examples demonstrate the superiority of LMS over LLS.     

Predicting digestibility of ammonia fiber explosion (AFEX)-treated rice straw

The enzymatic digestibility of ammonia fiber explosion (AFEX)-treated rice straw was modeled by statistically correlating the variability of samples to differences in treatment using several different analytical techniques. Lignin content and crystallinity index of cellulose affect enzymatic hydrolysis the most. X-ray diffraction was used to measure the crystallinity index (CrI), while fluorescence and diffuse reflectance infrared (DRIFT) spectroscopy measured the lignin content of the samples. Multivariate analysis was applied to correlate the enzymatic hydrolysis results of the various samples with X-ray diffraction and spectroscopic data. Principal component analysis (PCA) and multilinear regression (MLR) techniques did not accurately predict the digestibility of the rice straw samples. The best correlation (R value of 0.775) was found between the treatment conditions of the AFEX process and the concentration of xylose at 24 h after enzymatic hydrolysis.     

Structural determinants of inhibitor selectivity in prokaryotic IMP dehydrogenases

The protozoan parasite Cryptosporidium parvum is a major cause of gastrointestinal disease; no effective drug therapy exists to treat this infection. Curiously, C. parvum IMPDH (CpIMPDH) is most closely related to prokaryotic IMPDHs, suggesting that the parasite obtained its IMPDH gene via horizontal transfer. We previously identified inhibitors of CpIMPDH that do not inhibit human IMPDHs. Here, we show that these compounds also inhibit IMPDHs from Helicobacter pylori, Borrelia burgdorferi, and Streptococcus pyogenes, but not from Escherichia coli. Residues Ala165 and Tyr358 comprise a structural motif that defines susceptible enzymes. Importantly, a second-generation CpIMPDH inhibitor has bacteriocidal activity on H. pylori but not E. coli. We propose that CpIMPDH-targeted inhibitors can be developed into a new class of antibiotics that will spare some commensal bacteria.     

Complexation kinetics of Fe2+ with 1,10‐phenanthroline forming ferroin in acidic solutions

The formation kinetics of ferroin is studied under varied acid conditions at 25°C and fixed ionic strength (0.48 mol dm^?3) under pseudo‐first‐order conditions with respect to Fe²⁺ by using the stopped‐flow technique. The reaction followed is first and third order with respect to Fe²⁺ and 1,10‐phenanthroline (phen)_T, respectively. Increasing the acid concentration retarded the reaction, and the reaction rate showed a positive salt effect. The rate‐limiting step involved the complexation of the phen or protonated phen with [Fe(phen)₂]²⁺ complex ion, leading to formation of [Fe(phen)₃]²⁺ ion. The observed retardation of the reaction rate with increasing [H⁺]₀ is due to the increased [phenH⁺]_eq and low reactivity of phenH⁺ with [Fe(phen)₂]²⁺ complex ion. Simulated curves for the acid variation experiments agreed well with the corresponding experimental curves and the estimated rate coefficients supporting the proposed mechanism. Relatively low energy of activation (26 kJ mol^?1) and high negative entropy of activation (?159.8 J K^?1 mol^?1) agree with the proposed mechanism and the formation of compact octahedral complex ion. © 2008 Wiley Periodicals, Inc. 40: 515–523, 2008     

Photoinduced charge separation in three-layer supramolecular nanohybrids: fullerene-porphyrin-SWCNT

Photoinduced charge separation processes of three-layer supramolecular hybrids, fullerene-porphyrin-SWCNT, which are constructed from semiconducting (7,6)- and (6,5)-enriched SWCNTs and self-assembled via π-π interacting long alkyl chain substituted porphyrins (tetrakis(4-dodecyloxyphenyl)porphyrins; abbreviated as MP(alkyl)(4)) (M = Zn and H(2)), to which imidazole functionalized fullerene[60] (C(60)Im) is coordinated, have been investigated in organic solvents. The intermolecular alkyl-π and π-π interactions between the MP(alkyl)(4) and SWCNTs, in addition, coordination between C(60)Im and Zn ion in the porphyrin cavity are visualized using DFT calculations at the B3LYP/3-21G(*) level, predicting donor-acceptor interactions between them in the ground and excited states. The donor-acceptor nanohybrids thus formed are characterized by TEM imaging, steady-state absorption and fluorescence spectra. The time-resolved fluorescence studies of MP(alkyl)(4) in two-layered nanohybrids (MP(alkyl)(4)/SWCNT) revealed efficient quenching of the singlet excited states of MP(alkyl)(4) ((1)MP*(alkyl)(4)) with the rate constants of charge separation (k(CS)) in the range of (1-9) × 10(9) s(-1). A nanosecond transient absorption technique confirmed the electron transfer products, MP˙(+)(alkyl)(4)/SWCNT˙(-) and/or MP˙(-)(alkyl)(4)/SWCNT˙(+) for the two-layer nanohybrids. Upon further coordination of C(60)Im to ZnP, acceleration of charge separation via(1)ZnP* in C(60)Im→ZnP(alkyl)(4)/SWCNT is observed to form C(60)˙(-)Im→ZnP˙(+)(alkyl)(4)/SWCNT and C(60)˙(-)Im→ZnP(alkyl)(4)/SWCNT˙(+) charge separated states as supported by the transient absorption spectra. These characteristic absorptions decay with rate constants due to charge recombination (k(CR)) in the range of (6-10) × 10(6) s(-1), corresponding to the lifetimes of the radical ion-pairs of 100-170 ns. The electron transfer in the nanohybrids has further been utilized for light-to-electricity conversion by the construction of proof-of-concept photoelectrochemical solar cells.     

Data,knowledge and method bases in chemical sciences. Part IV. Current status in databases

Computer readable databases have become an integral part of chemical research right from planning data acquisition to interpretation of the information generated. The databases available today are numerical, spectral and bibliographic. Data representation by different schemes--relational, hierarchical and objects--is demonstrated. Quality index (QI) throws light on the quality of data. The objective, prospects and impact of database activity on expert systems are discussed. The number and size of corporate databases available on international networks crossed manageable number leading to databases about their contents. Subsets of corporate or small databases have been developed by groups of chemists. The features and role of knowledge-based or intelligent databases are described.