Clavulanic acid and cephamicin c: a perspective of the biosynthesis, isolation and action mechanism

The present article reviews different aspects of the chemistry of two widely used β-lactam antibiotics Clavulanic Acid and Cephamycin C. The article discusses important details of the biosynthesis of these compounds, their action mechanism and, principally, the methods employed in their isolation and purification, in accordance with the available literature. Despite the large quantity of available articles and patents concerning β-lactam antibiotics, those which describe the isolation and purification of Clavulanic Acid and Cephamycin C are rare. Overall, the intention of this article is to discuss the up-to-date scientific research related to the compounds under review.FAPESPCNPqCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

A quantum chemical study on a set of non-imidazole H(3) antihistamine molecules

Molecular orbital calculations were carried out on a set of 28 non-imidazole H(3) antihistamine compounds using the Hartree-Fock method in order to investigate the possible relationships between electronic structural properties and binding affinity for H3 receptors (pK(i)). It was observed that the frontier effective-for-reaction molecular orbital (FERMO) energies were better correlated with pK(i) values than highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy values. Exploratory data analysis through hierarchical cluster (HCA) and principal component analysis (PCA) showed a separation of the compounds in two sets, one grouping the molecules with high pK(i) values, the other gathering low pK(i) value compounds. This separation was obtained with the use of the following descriptors: FERMO energies (epsilon(FERMO)), charges derived from the electrostatic potential on the nitrogen atom (N(1)), electronic density indexes for FERMO on the N(1) atom (Sigma((FERMO))c(i)(2)). and electrophilicity (omega`). These electronic descriptors were used to construct a quantitative structure-activity relationship (QSAR) model through the partial least-squares (PLS) method with three principal components. This model generated Q(2) = 0.88 and R(2) = 0.927 values obtained from a training set and external validation of 23 and 5 molecules, respectively. After the analysis of the PLS regression equation and the values for the selected electronic descriptors, it is suggested that high values of FERMO energies and of Sigma((FERMO))c(i)(2), together with low values of electrophilicity and pronounced negative charges on N(1) appear as desirable properties for the conception of new molecules which might have high binding affinity. 2010 Elsevier Inc. All rights reserved.CAPESCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The generator coordinate method in the unrestricted Hartree-Fock formalism

The generator coordinate method was implemented in the unrestricted Hartree-Fock formalism. Weight functions were built from Gaussian generator functions for 1s, 2s, and 2p orbitals of carbon and oxygen atoms. These weight functions show a similar behavior to those found in the generator coordinate restricted Hartree-Fock method, i.e., they are smooth, continuous, and tend to zero in the limits of integration. Moreover, the weight functions obtained are different for spin-up and spin-down electrons what is a result from spin polarization. (C) 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012CNPqCNPqFAPESPFAPESPCAPESCAPE

Precipitation reaction of clavulanic acid: thermodynamic and electronic study

In the present article the theoretical calculation of thermodynamic parameters for the two main precipitation agents, potassium 2-ethylhexanoate and t-octylamine, employed by the pharmaceutical industry to obtain potassium clavulanate for clinical use, is described. The results obtained using the standard thermochemistry calculation in the Gaussian package and by calculation of the reactivity indexes of the reagents and products are compared. The calculated thermodynamic parameters indicate that the reactivity indexes present a better correlation with the experimentally obtained percentage yield. In addition, a series of additional precipitation agents that are also used in industrial procedures to obtain potassium clavulanate for clinical use, were compared. This was done to verify if any present, a priori, better properties than potassium 2-ethylhexanoate or t-octylamine. The consistency of the reactivity indexes calculated clearly suggests that the methodology employed can be used to screen future precipitation agents for possible use in the production of potassium clavulanate

PRECIPITATION REACTION OF CLAVULANIC ACID: THERMODYNAMIC AND ELECTRONIC STUDY

In the present article the theoretical calculation of thermodynamic parameters for the two main precipitation agents, potassium 2-ethylhexanoate and t-octylamine, employed by the pharmaceutical industry to obtain potassium clavulanate for clinical use, is described. The results obtained using the standard thermochemistry calculation in the Gaussian package and by calculation of the reactivity indexes of the reagents and products are compared. The calculated thermodynamic parameters indicate that the reactivity indexes present a better correlation with the experimentally obtained percentage yield. In addition, a series of additional precipitation agents that are also used in industrial procedures to obtain potassium clavulanate for clinical use, were compared. This was done to verify if any present, a priori, better properties than potassium 2-ethylhexanoate or t-octylamine. The consistency of the reactivity indexes calculated clearly suggests that the methodology employed can be used to screen future precipitation agents for possible use in the production of potassium clavulanate