Microenvironmental kinetic effects within a lyotropic smectic biophase model: conformational restrictions in Fischer indole cyclization.
The microenvironmental orientation effects, arising from an orderer solvent structure, were studied in a model liquid crystalline biophase for the cyclization of a series of 2-substituted cyclohexanone phenylhydrazones. The magnitude of such solvent-induced intramolecular conformational constraints were determined from a comparison of the kinetics of the Fischer indole rearrangement in a lyotropic smectic liquid crystal versus those in an isotropic liquid of similar chemical composition but lacking the structured nature of the mesophase. Solutions consisting of 50% (w/w) polyoxyethylene 6 tridecyl ether or 44% (w/v) polyethylene glycol in aqueous buffers comprised the smectic or isotropic media, respectively. The apparent dissociation constants of the conjugate acids of the phenylhydrazones were determined kinetically, as were their partition coefficients between lipid and polar isotropic phases approximating the compositions of the smectic lamellae. Intrinsic first-order rate constants, corrected for partitioning within the lamellar mesophase, were used to compute the enthalpies and entropies of activation. The somewhat slower intrinsic rates of cyclization and the accompanying less negative entropies of activation generally observed in the liquid crystalline medium, as opposed to the isotropic system, are attributed to the orienting effects of the lamellar lyotropic mesophase.
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003500:Cyclization; D003512:Cyclohexanones; D066298:In Vitro Techniques; D007211:Indoles; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D011092:Polyethylene Glycols; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D003512:Cyclohexanones; D007211:Indoles; D012997:Solvents; D011092:Polyethylene Glycols; C013458:cyclohexanone phenylhydrazone