Optical enrichment of a racemic chiral crystal by X-ray irradiation
GENERATION of optical activity in a racemic mixture of enantiomers, a process relevant to the origin of life and of naturally chiral compounds1, requires chirality in the interaction responsible for the transformation or the environment in which it occurs. Without violating this strict requirement, we have found a way in which optical enrichment of a racemic mixture can occur without any chiral specificity in the mechanism. A racemic mixture of (1-cyanoethyl)(piperidine)cobaloxime, which contains the chiral 1-cyanoethyl group, crystallizes in a chiral space group (P212121) in which R and S enantiomers occupy crystallographically distinct (diastereoisomeric) positions in the asymmetric unit cell. We have prepared single crystals of the D configuration. Irradiating the crystal with X-rays at 343 K causes racemization of the S en-antiomer while the R enantiomer remains unaltered. This racemization is thought to be due solely to the different volume constraints on the two enantiomers in their different crystal environments. The result is that the number of R molecules is increased at the expense of S, and so the overall composition of the crystal changes from racemic to enriched in the R enantiomer.
Topochemistry for preparing ligands that dimerize receptors.
BACKGROUND
The cyclic, disulfide-containing peptide, cyclo-Ac-[Cys-His-Pro-Gln-Gly-Pro-Pro-Cys]-NH2, binds to streptavidin with high affinity. In streptavidin-peptide cocrystals of space group I222, cyclic peptide monomers are bound on adjacent streptavidin tetramers related by a crystallographic two-fold symmetry axis. We set out to determine whether the disulfide bonds of the peptide, presented close to one another in the crystal, could undergo disulfide interchange to form a dimer.


RESULTS
When juxtaposed, the disulfides of neighboring peptides undergo disulfide interchange, breaking and forming covalent disulfide bonds, to produce a peptide dimer adopting the symmetry of the crystal. This is the first example of a chemical transformation mediated by a protein crystal lattice. The structure of the streptavidin-bound monomer, and that of the dimer that was eventually produced from it in the crystal, were both determined from the same single crystal studied at different times. The two-fold symmetric peptide dimer was independently synthesized and shown to form crystals of dimerized streptavidin.


CONCLUSIONS
We have shown that formation of a covalently linked peptide dimer can be mediated by a protein crystal lattice. The dimer thus produced dimerizes its target, streptavidin, suggesting that solid-state (or topochemical) reactions of this kind may be broadly useful for the preparation of ligands that can dimerize other protein targets.
Photochemical electron transfer reactions in alkylcobaloximes
Abstract It is shown that photolysis with visible light (λ > 420 nm) of any alkylcobaloxime procedes via a mechanism involving an initial electron transfer reaction from an equatorial ligand to the central metal to produce a cobalt(II) species which retains both original axial ligands. In a subsequent rearrangement of the equatorial ligand a hydrogen atom is ejected.