nitrophenols and naphthyl-acetate

Microcalorimetry, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC-MS) have been used to conduct a thermodynamic investigation of the hydrolysis reactions {1-naphthyl acetate(aq) + H(2)O(l) = 1-naphthol(aq) + acetate(aq)}, {4-nitrophenyl acetate(aq) + H(2)O(l) = 4-nitrophenol(aq) + acetate(aq)}, and {4-nitrophenyl α-L-arabinofuranoside(aq) + H(2)O(l) = L-arabinose(aq) + 4-nitrophenol(aq)}. Calorimetrically determined enthalpies of reaction Δ(r)H(cal) were measured for all three reactions. However, since the positions of equilibrium for all of these reactions were found to lie very far to the right, it was only possible to set lower limits for the values of the apparent equilibrium constants K'. A chemical equilibrium model, together with pKs and standard enthalpies of reaction Δ(r)H° for the H(+) binding reactions of the reactants and products, was then used to calculate the values of Δ(r)H° for chemical reference reactions that correspond to the overall biochemical reactions that were studied experimentally. The values of Benson estimates of Δ(r)H° for the chemical reference reactions that correspond to the first of the above two reactions were, in all cases, within 16 kJ·mol(-1) of the results obtained in this study. Thermochemical network calculations led to Δ(f)H° = -286.4 kJ·mol(-1) for 1-naphthyl acetate(aq) and Δ(f)H° = -364.9 kJ·mol(-1) for 4-nitrophenyl acetate(aq).

Topics: Acetates; Arabinose; Glycosides; Hydrolysis; Molecular Structure; Naphthols; Nitrophenols; Thermodynamics

Many topically applied drugs contain esters that are hydrolyzed in the skin. Minipigs have emerged as potential models of human dermatology and, in some aspects, may be superior to commonly used rat skin. The aims of this study were to evaluate the suitability of minipig and rat skin as in vitro models of human epidermal esterase activity.. Naphthyl acetate and para-nitrophenyl acetate were tested as prototypical substrates of carboxylesterases from skin, plasma, and liver. Reaction products were monitored by high-performance liquid chromatography/ultraviolet analysis.. Hydrolysis efficiency in skin was higher than plasma, but lower than liver. The esterase efficiency of rat skin microsomes (580-1100 min(-1) mg(-1)) was two to three orders of magnitude higher than human (1.3-4.2 min(-1) mg(-1)) and minipig microsomes (1.2-4.2 min(-1) mg(-1)). Rat skin cytosol (80-100 min(-1) mg(-1)) was 2- to 10-fold more efficient than human (2.4-67 min(-1) mg(-1)) or minipig cytosol (18-61 min(-1) mg(-1)). Most importantly, human skin fractions displayed kinetics of hydrolysis very similar to minipig skin.. These studies show minipig skin as an appropriate, potentially valuable model for human epidermal ester metabolism and support the use of minipig skin in preclinical development of topically applied compounds.

Topics: Acetylcholinesterase; Animals; Blood; Carboxylesterase; Cholinesterase Inhibitors; Humans; In Vitro Techniques; Kinetics; Liver; Male; Naphthols; Neostigmine; Nitrophenols; Phenotype; Rats; Rats, Sprague-Dawley; Skin; Species Specificity; Swine; Swine, Miniature