Electroweak Parity-Violating Energy Shifts of Amino Acids: The “Conformation Problem”

Abstract

The preceding paper described our coupled-perturbed Hartree-Fock (CPHF) and density functional theory (DFT) methods of computing the parity-violating energy shift (PVES). This paper addresses the "conformation problem"-the difficulty determining which hand of amino acids in solution is favoured by the weak force due to the difficulty determining the solution conformation. We attempt to resolve this by using the methods of the preceding paper to compute the PVES of solution and gas-phase amino acid structures determined by other groups from high level optimizations that include solvation. We conclude that the conformational hypersensitivity of the PVES still precludes a definite conclusion as to the sign of the PVES of L-alanine in solution, but that there is no problem in the gas phase: the PVES of gas-phase L-alanine is decisively negative. We show that the PVES is very sensitive to certain torsion angles, but is not hypersensitive to bondlengths or bond angles. In determining structures for PVES computations, there is therefore no need for expensive full optimizations: one can just optimize the crucial torsion angles. We present new computations of gas-phase amino acids PVESs, using partial optimizations with small basis sets, and the results agree well with those from higher level techniques. In the following paper we apply these less costly techniques to larger amino acids. The "conformation problem" has led some to dismiss the PVES as the source of life's handedness, but we believe this is premature: we show here that amino acids are a special case because their favoured conformations are almost achiral.

Parity-Violating Energy Shifts of Murchison L-Amino Acids are Consistent with an Electroweak Origin of Meteorite L-Enantiomeric Excesses

“…The PVES varies quasi-sinusoidally with φ (see Fig. 3 of preceding paper, MacDermott et al 2009b) and the lowest SCF energy occurs very close to the point where the PVES changes sign with φ. The favoured conformation is of "HHO" type (see Figs.…”

“…In the previous paper (MacDermott et al 2009b) we showed that it was impossible to reach any conclusion about the sign of the PVES of zwitterionic L-alanine due to a "conspiracy" of three separate phenomena: (1) difficulty determining the correct solution conformation; (2) the conformational hypersensitivity of the PVES; (3) the fact that favoured conformations of amino acids just happen to be highly symmetrical, resulting in PVESs close to zero. The central problem is the difficulty determining the effect of solvation: we showed that numerous proposed conformations of L-alanine-determined by other groups based on very high-level solvent modelling and comparison with experiment (e. g. Tajkhorshid et al 1998;Frimand et al 2000)-gave PVESs that were almost equally divided between positive and negative.…”

“…5a, 6a, 7a of previous paper), with φ(O-C-C α -H) ≈ 60 • and η(H-N-C α -C) ≈ 180 • , so that two amino hydrogens hydrogenbond to the carboxyl oxygen, producing a highly symmetrical conformation. Note that we did not include solvation effects in our computations of the SCF energy of alanine (MacDermott et al 2009b), because we considered it futile in view of the failure of much higher-level computations by other groups to come to any consensus as to the solution conformation of amino acids. It was clear from our computations for terrestrial amino acids that the difference in SCF energy between the conformation with the most negative PVES and that with the most positive PVES (as φ is varied) was typically 10-20 kT R (where T R = 298K), which is comparable to hydrogen-bond energies, thus leaving the PVES highly vulnerable to sign change on solvation.…”

“…In the hope that this might be so, we computed the PVES of the four Murchison α-methyl amino acids-L-isovaline (L-isoValZ), L-α-methylnorvaline (L-αmnorValZ), (3R,2S)2-amino-2,3-dimethylpentanoic acid (rSadmpaZ), and (3S,2S)2-amino-2,3-dimethylpentanoic acid (sSadmpaZ)-in their zwitterionic (Z) form RC(CH 3 )(NH + 3 )COO − (but in vacuo, i.e. without consideration of solvation effects), using the method shown in the previous paper (MacDermott et al 2009b) to give good results for alanine, namely CoupledPerturbed Hartree-Fock with a 6-31G basis set. We showed in that paper that the PVES is hypersensitive to certain torsion angles, but not to bond angles and bondlengths, which can be set to generic values.…”

An alternative route to detect parity violating energy differences through Bose–Einstein condensation of chiral molecules

“…17 We note that, although the PVED has been proposed to tip the balance away from racemic mixtures toward an enhancement that could be incorporated into primitive forms of life, this energy difference is extremely small, so that amplification of some sort would be required to produce a detectable effect at a macroscopic level. However, in a recent work, MacDermott and coworkers 18 conclude that parity-violation does indeed favour the neutral L form of the a-methyl amino acids found to show L-excesses in the Murchison meteorite.…”