Nitrogen inversion

Abstract: The nuclear magnetic resonance spectra of various cyclic imines ranging in ring size from three to six have been examined. The spectra of N-substituted aziridine (ethplenimine) derivatives were found to be strongly temperature dependent as would be expected if the nitrogen atoms and attached groups do not lie in a plane and inversion occurs rather slowly. It has been possible to evaluate some factors which affect the inversion rates of non-planar nitrogen atoms in cyclic imines. As mould be expected, attachment of unsaturated groups to non-planar nitrogen increases the inversion rate as the result of conjugation with the nitrogen unshared electron pairs. The rates are also increased by bulky groups whether attached to nitrogen or to the carbons of the imine ring. Substitution of alkyl groups for one hydrogen or for two cis-hydrogens attached to carbon appears to make the molecules assume preferred Configurations with the N-substituent trans to the ring substituent (s). The inversion rates most probably are decreased in hydroxylic solvents because of stabilization of the separate configurations by hydrogen bonding between the solvent and the imino nitrogen. The data so far obtained indicate that substituted aziridines with molecular asymmetry due to trivalent nitrogen are likely only to be resolvable into reasonably stable optical antipodes at temperatures below - 50o. The nitrogen inversion rates of N-substituted azetidines (trimethylenimines) and larger-ring imines appear to be too great to be measurable by nuclear magnetic resonance techniques at temperatures above-77o.

Abstract: Compounds containing the C==N group, such as imines and their derivatives, may undergo syn-anti isomerization by two different routes: 1) photochemically, by out-of-plane rotation around the carbon-nitrogen double bond through a "perpendicular" form, and 2) thermally, by in-plane nitrogen inversion through a "linear" transition state. When the two interconversions occur in sequence, a full, closed process is accomplished, restoring the initial state of the system along two different steps. In a chiral imine-type compound, for example, with an asymmetric center next to the C==N function, photoinduced rotation may be expected to occur in one sense in preference to the opposite one. Thus, photoisomerization followed by thermal isomerization in a chiral imine compound generates unidirectional molecular motion. Generally, imine-type compounds represent unidirectional molecular photomotors converting light energy into mechanical motion. As they are also able to undergo exchange of the carbonyl and amine partners, they present constitutional dynamics. Thus, imine-type compounds are double dynamic, motional, and constitutional devices.

Abstract: The X-ray crystal structures of native penicillopepsin and of its complex with a synthetic analogue of the inhibitor pepstatin have been refined recently at 1.8-A resolution. These highly refined structures permit a detailed examination of peptide hydrolysis in the aspartic proteinases. Complexes of penicillopepsin with substrate and catalytic intermediates were modeled, by using computer graphics, with minimal perturbation of the observed inhibitor complex. A thallium ion binding experiment shows that the position of solvent molecule O39, between Asp-33(32) and Asp-213(215) in the native structure, is favorable for cations, a fact that places constraints on possible mechanisms. A mechanism for hydrolysis is proposed in which Asp-213(215) acts as an electrophile by protonating the carbonyl oxygen of the substrate, thereby polarizing the carbon-oxygen bond, a water molecule bound to Asp-33(32) (O284 in the native structure) attacks the carbonyl carbon as the nucleophile in a general-base mechanism, the newly pyramidal peptide nitrogen is protonated, either from the solvent after nitrogen inversion or by an internal proton transfer via Asp-213(215) from a hydroxyl of the tetrahedral carbon, and the tetrahedral intermediate breaks down in a manner consistent with the stereoelectronic hypothesis. The models permit the rationalization of observed subsite preferences for substrates and may be useful in predicting subsite preferences of other aspartic proteinases.