4P070

Chirality Transfer Mechanism for Optical D/L Lactic AcidIsomers: A theoretical Study Based on the Scaled
Hypersphere Search Method(Graduate School of Science, Tohoku University) ○Xia Yang, Satoshi Maeda, Koichi Ohno

Lactic acid is chiral and has two optical isomers. One is known as L-(+)-lactic acid or (S)-lactic acidand the other, its mirror image, is D-(-)-lactic acid or (R)-lactic acid. L-(+)-Lactic acid is the biologicallyimportant isomer. Molecular chirality is one of the fundamental characteristics of molecules, and it plays
an important role in stereochemistry and biochemisty. Specifically, the homo-chirality of biologicalmolecules (the use of only left-handed L-configuration amino acids and only right-handed D-configurationsugars) has long been known to be an important characteristic of life. Notable problems endure regarding
the molecular evolution, which culminated in the homo-chiral biopolymers associated with contemporary
terrestrial life. How was Nature’s selection of these stereochemical structures, a random one, or weredeterminate processes involved? All these questions urged us to investigate their reaction pathways on
potential energy surface (PES), which is a fascinating research goal.
The Scaled hypersphere search (SHS) method [1-3] makes it possible to explore unknown reaction
pathways on PES. This method enables us to make a global analysis of the potential energy surface bydetecting the anharmonic downward distortions of PES as energy minima on a hyper surface which would
have a constant energy if the potentials are harmonic. In this study, intramolecular D-L conversion
pathways of lactic acid have been discovered by the application of the SHS method to exploring potential
energy surfaces at the level of HF/6-31G based on a Gaussian03 program package. From each TS,
downhill techniques toward both sides were carried out to determine the minimum energy path or theintrinsic reaction coordinate (IRC).
Fig.1 shows D-L conversion pathways between optical isomers of lactic acid. Starting from one of themost stable isomer with point chirality, reaction pathways leading to neighboring transition state weresearched systematically from its equilibrium structure. As can be seen in Fig.1, four conversion channels,(A), (B), (C), and (D), were discovered between D and L lactic acid. No direct conversion channel via only
one TS exists between D and L isomers of lactic acid.
Channel (a) includes two types of dissociated achiral intermediate states with Cs symmetry that are ofhydrogen-bond characters. Similar to the channel (C) in D-L conversion of Alanine [4], Channel (b)surmounts a chiral transition state to descend to an intermediate with axial chirality, which is thentransformed to its counterpart with the opposite chirality via an achiral transition state with Cs symmetry.
Channel (c) and (d) show processes from the lactic acid to another two intermediates via the cleavage ofC-O bond and the formation of H2O. Actually, Channel (c) is a pathway via a chiral transition state into anintermediate with helical chirality, while Channel (d) is a process via an intermediate with axial chirality,
corresponding to channel (B) and (D) in D-L conversion of Alanine [4], respectively. The present results
show channel (a) in this study is a newly found pathway.
Since the first transition state in every channel has a high barrier larger than 200 kJ/mol, lactic acidmolecule is kinetically stable enough to keep its own chirality under thermally mild conditions. The

preference of D-L conversion routes is expected as (a)>(b)>(c)>(d) from the magnitudes of the barrierheights of respective transition state. Since the inter-conversion of four functional groups around theasymmetric carbon atom (C*) can be summarized into a combination of two functional groups, which canrotate to its counterpart to yield the other optical isomer with the opposite chirality, as shown in Ref. [4], inthis study, the rotation of four couple of functional groups around the asymmetric carbon atom of lactic
acid, (OH, COOH), (H, COOH), (H, OH), and (CH3, COOH) are allowed for the D-L conversion channelsof (a), (b), (c), and (d), respectively.
(a)
TS (262.3KJ/mol) TS (262.3KJ/mol)

TS (288.5KJ/mol) TS (288.5KJ/mol)intermediate (Cs)intermediate (Cs)(209.8KJ/mol)(210.0KJ/mol)

L-lactic acidD-lactic acidL-lactic acid

(0.0KJ/mol)(0.0KJ/mol)(0.0KJ/mol)D-lactic acid
(0.0KJ/mol)(b)
TS (314.76)

TS (314.76)

TS (Cs) (78.7KJ/mol)

L-lactic acid

Intermediate

intermediate(52.5KJ/mol)(52.5KJ/mol)(0.0KJ/mol)D-lactic acid
(0.0KJ/mol)

(c)

(d)

TS
367.2KJ/mol

TS
intermediate

419.4KJ/mol

262.3KJ/mol

lactic acid 0.0KJ/mol

lactic acid 0.0KJ/mol
Fig1. D-L Conversion pathways between optical isomers of lactic acid.
[1] K.Ohno, S. Maeda, Chem. Phys. Lett. 384, 277 (2004)[2] S. Maeda, K.Ohno, J. Phys. Chem, A 109, 5742 (2005)[3] K.Ohno, S. Maeda, J. Phys. Chem, A 110, 8933 (2006)[4] K.Ohno, S. Maeda, Chem. Letters. 35, 492 (2006)

intermediate
52.5KJ/mol