RESUMO
Multiparameter linear energy-density relationships to model solvent effects in room temperature ionic liquids (RTILs) are introduced and tested. The model incorporates two solvent dependent and two specific solute-solvent parameters represented by a set of electronic indexes derived from the conceptual density functional theory. The specific solute-solvent interactions are described in terms of the electronic chemical potential for proton migration between the anion or cation and the transition state structure of a specific reaction. These indexes provide a quantitative estimation of the hydrogen bond (HB) acceptor basicity and the hydrogen bond donor acidity of the ionic solvent, respectively. A sound quantitative scale of HB strength is thereby obtained. The solvent dependent contributions are described by the global electrophilicity of the cation and nucleophilicity of the anion forming the ionic liquid. The model is illustrated for the kinetics of cycloaddition of cyclopentadiene towards acrolein. In general, cation HB acidity outweighs the remaining parameters for this reaction.
Assuntos
Acroleína/síntese química , Ciclopentanos/química , Líquidos Iônicos/química , Teoria Quântica , Acroleína/química , Ligação de Hidrogênio , Cinética , Estrutura Molecular , Solventes/químicaRESUMO
In analogy with Sanderson's electronegativity equalization principle, it is possible to postulate a principle of spin potential equalization in the E[N(alpha), N(beta)] representation of the spin polarized density functional theory, where N(alpha) and N(beta) refer to the number of electrons with spins alpha and beta, respectively. The principle provides simple expressions to evaluate the energy changes DeltaE between two interacting molecules, A and B, together with the electron transfer, DeltaN(alpha) and DeltaN(beta). The model is illustrated for a series of addition reactions of electrophilic, nucleophilic, and ambiphilic carbenes to alkenes in their singlet and triplet multiplicities. The results are in a consistent qualitative agreement with the experimental reactivity established for these systems.
RESUMO
INTRODUCTION: Low-molecular-weight heparins are commonly used for the prophylaxis of thromboembolic disease. In contrast to therapeutic doses, recommended prophylactic doses are fixed (i.e., 40 mg/day enoxaparin). Dosing of patients with extreme body weights has not been well studied, especially dosing of low weight patients. OBJECTIVES: To establish the anti-Xa activity that results from 40 mg/day enoxaparin in inpatients with body weight ≤ 55 kg. PATIENTS/METHODS: Cross-sectional study including inpatients older than 18 years, with body weight ≤ 55 kg, and whose treating physician found indication for 40 mg/day enoxaparin. We excluded patients with renal failure and those using oral anticoagulants. Anti-Xa activity was measured 3 hours after the second dose of enoxaparin. Statistical analyses were conducted to determine the effect of body weight on anti-Xa levels. RESULTS: Average age was 72.5 years (interquartile range, 30) and median body weight was 49.7 kg (interquartile range, 7). Twenty-five percent of patients weighed ≤ 45 kg, 37.5% weighed 46-50 kg, and 37.5% weighed 51-55 kg. The mean anti-Xa activity was 0.54±0.18IU/ml, and 60% of the patients exhibited activity ≥0.5 IU/ml. Weight and anti-Xa activity inversely correlated (Spearman's rho=-0.428, p=0.001). Patients weighing ≤ 45 kg exhibited higher anti-Xa activity (0.61±0.18 IU/ml, p=0.008) than heavier patients and an odds ratio of 8 for anti-Xa level ≥0.5IU/ml (95% CI: 1.42-45.06). CONCLUSIONS: Anti-factor Xa activity rises significantly when body weight decreases. Patients of low weight, especially those weighing <45 kg, exhibited an anti-Xa activity higher than the desired range for thromboembolic prophylaxis.
Assuntos
Anticoagulantes/uso terapêutico , Peso Corporal/efeitos dos fármacos , Enoxaparina/uso terapêutico , Fator Xa/metabolismo , Tromboembolia Venosa/prevenção & controle , Idoso , Estudos Transversais , Feminino , Hospitalização , Humanos , Masculino , Estudos Prospectivos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/tratamento farmacológicoRESUMO
We introduce and test a nucleophilicity index as a new descriptor of chemical reactivity. The index is derived from a perturbation model for the interaction between the nucleophile and a positive test charge. The computational implementation of the model uses an isoelectronic process involving the minimum values of the electronic part of the perturbed molecular electrostatic potential. The working expression defining the nucleophilicity index encompasses both the electrostatic contributions and the second-order polarization effects in a form which is consistent with the empirical scales previously proposed. The index is validated for a series of neutral nucleophiles in the gas phase for which the nucleophilicity pattern has been experimentally established within a spectroscopic scale.
RESUMO
The effect of 3 purified trypsin inhibitors and 4 legume seed extracts on teh trypsins and chymotrypsins of the activated pancreata of 11 animal species, including man, was measured. The activation was performed by either homologous enterokinase or by bovine trypsin. Several trypsinogens were not activated by the latter. Rabbit trypsin was the most sensitive to all inhibitor preparations, while the human trypsin was the most resistant, except to the black bean extract. The response of the chymotrypsins was more variable and those of capybara and rabbit showed extreme sensitivity. Considerable differences between the extracts of black and white garden beans, both Phaseolus vulgaris, with respect to their reactivity toward different animal enzymes were detected. No relation between relative pancreas weight and susceptibility toward soybean trypsin inhibitor could be observed.