Computational (DFT) and Experimental (NMR) Study of the Chelation of an Iridium Hyperpolarization Transfer Catalyst by Amino Acids

Abstract

Non‐hydrogenative Para‐Hydrogen Induced Hyperpolarization (nhPHIP) is a Nuclear Magnetic Resonance (NMR) hyperpolarization technique which has experimentally been used to analyze complex biological samples containing amino acids using the Ir‐IMes hyperpolarization transfer catalyst. A computational study based on Density Function Theory (DFT) was performed on all relevant stereoisomers of [Ir(H)2(IMes)(AA)(Py)] (with AA=glycine, alanine, valine; Py=pyridine), for which R/S chirality and orientation of the amino acid chelation (C/A) were considered. A total of 30 structures were calculated comprising of 6 stereoisomers for achiral glycine, and 12 stereoisomers for each of the chiral amino acids. The abundances derived from the DFT energies confirmed the trends observed in thermal (non‐hyperpolarized) NMR experiments. Additionally, theoretical calculations of electronic (Wiberg bond indices, Natural Bond Orders, Frontier Orbital Analysis), bond dissociation energies, transition states, and activation energies related to interconversion between binding modes, and steric factors (Solid angle) were performed to provide detailed explanations for NMR experimental observations.

Parahydrogen hyperpolarized NMR detection of underivatized short oligopeptides

“…Calculations showed that the binding pattern with N-terminus in ax and C-terminus oxygen in eq plane is the energetically favored bidentate l -Ala-catalyst-complex, in agreement with experimental results from Tessari group 28 as well as with the recent gas-phase DFT study, 34 further confirming strong prevalence of the bidentate ax–eq binding mode for alanine (see SI_DFT†). Additionally, according to DFT, there are two bidentate binding topologies of higher energy: reversed ax–eq and eq–eq (Fig.…”