The alkylating potential of -propiolactone (BPL), -butyrolactone (BBL), γ-butyrolactone, and δ-valerolactone, which can be formed by the in vivo nitrosation of primary amino acids, was investigated kinetically. The nucleophile NBP, 4-(p-nitrobenzyl)pyridine, a trap for alkylating agents, was used as an alkylation substrate. The alkylation reactions were performed under mimicked cellular conditions at neutral pH in water/dioxane solvent mixtures. To gain insight into the effect of the hydrolysis of lactones on their alkylating efficiency, alkylation and competing hydrolysis were studied in parallel. Conclusions were drawn as follows: (i) γ-Butyrolactone and δ-valerolactone afford neither appreciable NBP alkylation nor hydrolysis reactions; (ii) the alkylating potential of BPL is 10-fold higher than that of BBL, the reactivity of both being essentially enthalpy-controlled; (iii) a correlation was found between the alkylating potential of lactones and their carcinogenicity; (iv) the hydrolysis of lactones is not sufficiently effective to prevent alkylation; (v) the efficiency of alkylation, expressed as the alkylation rate/ hydrolysis rate ratio, decreases strongly with increasing amounts of dioxane in the reaction media; (vi) the absorption coefficients of the NBP-lactone adducts are as follows: NBP-BPL ) 5101 ( 111 M -1 cm -1 (λ ) 584 nm) and NBP-BBL ) 462 ( 19 M -1 cm -1 (λ ) 586 nm), the pronounced difference between these values being rationalized in terms of the adducts' structure; and (vii) linear correlations exist between the adducts' absorption coefficients and the water/dioxane ratio in the reaction media.
The neutral and base-catalyzed hydrolysis of nine carboxylic acid esters was studied using a hybrid supermolecule-PCM approach including six explicit water molecules. The molecules studied included two linear esters, four β-lactones, two γ-lactones, and one δ-lactone: ethyl acetate and methyl formate, β-propiolactone, β-butyrolactone, β-isovalerolactone, diketene (4-methyleneoxetan-2-one), γ-butyrolactone, 2(5H)-furanone, and δ-valerolactone. DFT and ab initio methods were used to analyze the features of the various possible hydrolysis mechanisms. For all compounds, reasonable to very good qualitative and quantitative agreement with experimental work was found, and evidence is provided to support long-standing hypotheses regarding the role of solvent molecule as a base catalyst. In addition, novel evidence is presented for the existence of an elimination-addition mechanism in the basic hydrolysis of diketene. A parallel work addresses the acid-catalyzed hydrolysis of lactones.
A statistical study of railway fastening insulating plates from various points of the Spanish territory reveals that high responsibility structural components injected with a hygroscopic material such as polyamide (PA) reinforced with short fiberglass can absorb varying amounts of water, depending on the working environment. This hygroscopic nature of PA6 means that the mechanical behavior of the matrix, and thus of the component as a whole, is heavily dependent on the content of water retained. This article studies the absorption and diffusion of water in the core of PA6. To verify the effects of humidity on the mechanical properties of reinforced PA6, the material was conditioned, that is, it was assigned a precise humidity content. The results obtained show that the interphase between the fiber and the matrix is a preferential way for the water advance in the composite. The diffusion of water in the PA core was carried out according to Fick's Second Law and the diffusion coefficient responds to an Arrhenius exponential law. The material behavior was experimentally validated and so it can be applied to quantify the humidity content of a component in a specific environment of temperature and exposure. POLYM. COMPOS., 26:580 -586,
2005.
Alkylating agents are considered to be archetypal carcinogens.
One suitable technique to evaluate the activity of alkylating compounds
is the NBP assay. This method is based on the formation of a chromophore
in the reaction between the alkylating agent and the nucleophile 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents
with nucleophilic characteristics similar to those of DNA bases. NBP
is known to react with strong and weak alkylating agents, and much
insight into such alkylation mechanisms in vivo can
be gained from kinetic study of some alkylation reactions in vitro. Since 1925, the NBP assay has evolved from being
a qualitative, analytical tool to becoming a useful physicochemical
method that not only allows the rules of chemical reactivity that
govern electrophilicity and nucleophilicity to be applied to the reaction
of DNA with alkylating agents but also helps to understand some significant
relationships between the structure of many alkylation substrates
(including DNA) and their chemical and biological responses. Given
that advances in this area have the potential to yield both fundamental
and practical advances in chemistry, biology, predictive toxicology,
and anticancer drug development, this review is designed to provide
an overview of the evolution of the NBP method from its early inception
until its recent kinetic–mechanistic approach, which allows
the pros and cons of NBP as a DNA-model to be analyzed. The validity
of NBP as a nucleophilicity model for DNA in general and the position
of guanosine at N7 in particular are discussed.
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