Hydrogen-Tunneling in Biologically Relevant Small Molecules: The Rotamerizations of α-Ketocarboxylic Acids

Abstract

Quantum mechanical tunneling governs the C-O bond rotamerization of simple alkyl and aryl carboxylic acid conformers at cryogenic temperatures. In this study, we report tunneling investigations on a series of electronically different α-ketocarboxylic acids including glyoxylic, pyruvic, cyclopropylglyoxylic, and phenylglyoxylic acid in solid Ar and Ne as host materials at temperatures ranging from 3 to 20 K. The higher-lying rotamers generated through photoirradiation with wavelengths of λ = 313 nm or λ > 850 nm convert to their low-energy conformers through hydrogen-tunneling, as evident from the time evolution of their infrared spectra, and the complete suppression of this process by deuteration. The conversion rates sensitively depend on the choice of matrix material and the tunneling half-lives range from a few hours to several days and are higher in Ne than in Ar for glyoxylic, pyruvic, and cyclopropylglyoxylic acid. The advent of tunneling in α-ketocarboxylic acids dominates their conformational preferences and conceivably also the reactivity of biologically and pharmacologically relevant acid congeners.

Atom Tunneling in Chemistry

“…Ring expansion as aresult of carbon tunneling, as observed in carbenes. [143,151,152] X = Cl,F Angewandte Chemie Reviews proton shifts.T unneling decay of particular conformers of glycine, [166,167] alanine, [168] cytosine, [169] and other small molecules with relevance to biology [170,171] was observed as well as the tunneling-accelerated tautomerization of tetrazole acetic acid. [172] Hydrogen peroxide is chiral if the rotation around the OÀObond is restricted at low temperature.The racemization was investigated by six-dimensional quantum dynamics [173] and shown to proceed efficiently by tunneling.…”

Conformational changes in matrix-isolated 6-methoxyindole: Effects of the thermal and infrared light excitations

“…[1][2][3][4] Two methodologies are commonly employed to alter the relative abundance of the trapped conformers: annealing of the sample 5,6 or subjecting it to narrowband or broadband radiation of the IR or UV spectral regions. 2,[7][8][9][10][11][12][13][14] In the first case, the population of less stable forms is reduced in favour of the most stable ones, providing that the energy barriers for the isomerizations can be surmounted. In the second case, the conformational interconversions may occur in both directions, thus permitting population and stabilization of very high energy conformers, which otherwise would be rather difficult to be experimentally detected.…”

“…In the second case, the conformational interconversions may occur in both directions, thus permitting population and stabilization of very high energy conformers, which otherwise would be rather difficult to be experimentally detected. 4,14,15 Very recently, we have investigated the conformational changes in matrix-isolated 6-methoxyindole (6MOI) induced by narrowband near-IR (NIR) excitation. 2 Using monochromatic laser radiation tuned at the frequency characteristic of the first NH stretching overtones of the two identified conformers (see their geometries in Figure 1), we were able to selectively shift the conformational composition in both directions.…”

Tunnelling in carbonic acid

“…1B) via TS2 exhibits a 34.6 kcal mol À1 barrier at the CCSD(T)/CBS level; this compares well with the QCISD(T)/6-311++G(d,p)//MP2(full)/ 6-31++G(d,p) barrier of 34.3 kcal mol À1 reported earlier. [38][39][40][41][42][43][44] We executed a detailed kinetic analysis of this tunnelling phenomenon in different noble gases and at various temperatures (Table 1). 1).…”