2-chloroethanol Infrared spectroscopic study of the secondary

2-chloroethanol formation as evidence for a 2-chloroethyl alkylating intermediate during chemical degradation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea

Chemical degradation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea or 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea in buffer under physiological conditions resulted in the formation of a significant quantity of 2-chlorethanol (18 to 25% of the initial nitrosourea concentration). Other degradation products observed included acetaldehyde (5 to 10%), vinyl chloride (1 to 2%), ethylene (1 to 2%), and cyclohexylamine (32%), but not 1,3-dicyclohexylurea. The 2-chlorethyl moiety of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was trapped with halide ions, CI-, BR-, and I-, to form the corresponding dihaloethanes which were identified by gas chromatography-mass spectrometry techniques. High-pressure liquid chromatographic procedures were developed for the separation and quantiation of the nitrosoureas and many of their degradation products. It is postulated that a new mode of 1(2-chloreoethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea degradation can occur that is not the loss of the chloro group as chloride ion, but the loss of the N-3 hydrogen as a proton. Then the corresponding isocyanate and 2-chloroethyidiazene hydroxide are formed, with the latter intermidiate becoming an alkylating specie

Infrared spectroscopic study of the secondary structure of melittin in water, 2-chloroethanol, and phospholipid bilayer dispersions.

The conformations of melittin, an amphipathic polypeptide consisting of 26 amino acid residues, and its hydrophobic (residues 1--19) and hydrophilic (residues 20--26) fragments were examined in various solvent systems, including H2O, 2H2O, 2-chloroethanol, and 1,2-dimyristoylphosphatidylcholine (DMPC) multilayers, by infrared spectroscopy. Water and 2-chloroethanol were used as reference solvents for characterizing the amide I and II vibrational frequencies of the polypeptide in systems reflecting unordered, beta-structure, or alpha-helical forms. In DMPC bilayer assemblies both melittin and its hydrophobic fragment F1 exhibit alpha-helical conformations. In contrast, infrared spectra for the hydrophilic F2 fragment are suggestive of a beta conformation with perhaps spectral contributions from random-coil configurations. The alpha-helical conformation of intact melittin in DMPC multilayer dispersions remains unchanged as the bilayer passes from the gel to liquid-crystalline state. For melittin-water solutions the infrared spectra monitor changes in population of specific conformations as the temperature is varied. Thus, for melittin concentrations in which tetramers are dominant high temperatures (31 degrees C) favor the alpha-helical form, while low temperatures (8 degrees C) lead to populations of both beta and alpha-helical structures. At lower melittin concentrations for which monomers persist, high temperatures favor an unordered polypeptide form, while low temperatures induce an alpha-helical conformation. Although peak-height intensity ratios AII/AI for the amide I and II regions are difficult to interpret rigorously, values of this parameter for aqueous solutions of melittin suggest a sensitivity to structural changes involving the aggregation properties of the polypeptide.