Interactions of arylhydroxylamines and alkylaldoximes with a rhodium porphyrin.

Heme enzymes are involved in the binding and metabolism of hydroxylamine (RNHOH) and aldoxime (RCH=NOH) compounds (R = H, alkyl, aryl). We report the synthesis and X-ray crystal structure of a metalloporphyrin in complex with an arylhydroxylamine, namely that of (TPP)Rh(PhNHOH)(C6H4Cl) (TPP = tetraphenylpophryinato dianion). The crystal structure reveals, in addition to N-binding of PhNHOH to Rh, the presence of an intramolecular H-bond between the hydroxylamine -OH proton and a porphyrin N-atom. Results from density functional theory (DFT) calculations support the presence of this intramolecular H-bond in this global minimum structure, and a natural bond order (NBO) analysis reveals that this H-bond comprises a donor π N=C (porphyrin) to acceptor σ* O-H (hydroxylamine) interaction of 2.32 kcal/mol. While DFT calculations predict the presence of similar intramolecular H-bond interactions in the related aldoxime complexes (TPP)Rh(RCH=NOH)(C6H4Cl) in their global minima structures, the X-ray crystal structure obtained for the (TPP)Rh(CH3(CH2)2CH=NOH)(C6H4Cl) complex is consistent with the local (non-global) minima conformation that does not have this intramolecular H-bond interaction.

Interactions of N-hydroxyamphetamine with an iron porphyrin: A unique intramolecular H-bond probed by DFT calculations.

Hydroxylamine (NH2OH) and its N-substituted derivatives (RNHOH) are important biological intermediates in the global N cycle. Heme plays a central role in the binding and activation of these hydroxylamines. We report the crystal structures of N-hydroxyamphetamine (AmphNHOH) in complex with Fe and Co heme models. We demonstrate a previously unrecognized internal H-bond interaction between a hydroxylamine RNHO-H group and a porphyrin N-atom. We utilize density functional theoretical (DFT) calculations to show that the conformations with the internal H-bond represent global minima along the potential energy surfaces for both the Fe and Co heme models. A natural bond orbital (NBO) analysis reveals a donor π (porN=C) to acceptor σ* (O-H) interaction of 3.04 kcal/mol for Fe, accounting for 11% of the total heme-AmphNHOH interaction energy. Our DFT calculations with the parent Fe-NH2OH suggests that the presence of internal H-bonds between hydroxylamine (R/H)NHOH moieties and heme N-atoms may be more common than previously recognized.