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Conchín Meliá Silvia Ferrer Vicent Moliner Iñaki Tuñón Juan Bertrán 《Journal of computational chemistry》2012,33(24):1948-1959
We are presenting a theoretical study of the hydrolysis of a β‐lactam antibiotic in gas phase and in aqueous solution by means of hybrid quantum mechanics/molecular mechanics potentials. After exploring the potential energy surfaces at semiempirical and density functional theory (DFT) level, potentials of mean force have been computed for the reaction in solution with hybrid PM3/TIP3P calculations and corrections with the B3LYP and M06‐2X functionals. Inclusion of the full molecule of the antibiotic, Cefotaxime, in the gas phase molecular model has been demonstrated to be crucial since its carboxylate group can activate a nucleophilic water molecule. Moreover, the flexibility of the substrate implies the existence of a huge number of possible conformers, some of them implying formation of intramolecular hydrogen bond interaction that can determine the energetics of the conformers defining the different states along the reaction profile. The results show PM3 provides results that are in qualitative agreement with DFT calculations. The free energy profiles show a step‐wise mechanism that is kinetically determined by the nucleophilic attack of a water molecule activated by the proton transfer to the carboxylate group of the substrate (the first step). However, since the main role of the β‐lactamase would be reducing the free energy barrier of the first step, and keeping in mind the barrier obtained from second intermediate to products, population of this second intermediate could be significant and consequently experimentally detected in β‐lactamases, as shown in the literature. © 2012 Wiley Periodicals, Inc. 相似文献
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Victoria F. Samanidou Emmanouil D. Tsochatzis Ioannis N. Papadoyannis 《Mikrochimica acta》2008,160(4):471-475
An HPLC method was developed and validated for the determination of the cephalosporins cefotaxime and cephalexine in skimmed
bovine milk. The analytical column, Kromasil C18 (250 mm × 4.0 mm, 5 μm) was operated at ambient temperature. Mobile phase consisted of CH3OH-acetate buffer (pH = 4.0) and it was delivered isocratically at a flow rate of 1.0 mL · min−1. Total analysis time was less than 5 min. Caffeine was used as internal standard (5 ng · μL−1). UV detection was performed at 265 nm. Method validation was performed by means of intra-day (n = 5) and inter-day accuracy and precision (n = 8), sensitivity and linearity. Limits of detection (LOD) and limits of quantification (LOQ) were 0.1 and 0.3 ng · μL−1, respectively. The method was applied to the analysis of a veterinary drug (CEPOREX) containing cephalexine. The results
were quite accurate with the relative error varying from −8.0 to −3.5%. Solid-phase extraction was applied to remove all matrix
interference from milk samples. High extraction recoveries (average 84–121%) were achieved by using Abselut NEXUS cartridges
with acetonitrile as eluent and a rinsing step with water and n-butanol. A pre-concentration step was necessary in a 1/10
level to reach the EU MRL concentration level (100 μg · kg−1). RSD values were less than 7% for both cephalosporins.
Correspondence: Ioannis N. Papadoyannis, Laboratory of Analytical Chemistry, Department of Chemistry, Aristotle University
of Thessaloniki, GR-54124 Thessaloniki, Greece 相似文献
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