DOI: 10.1002/chem.200902983 Solution-Phase Racemization in the Presence of an Enantiopure Solid Phase Cristobal Viedma,* [a] Bastiaan J. V. Verkuijl, [b] JosØ E. Ortiz, [d] Trinidad de Torres, [d] Richard M. Kellogg,* [c] and Donna G. Blackmond* [b, e] Introduction One of the greatest unsolved problems in chemistry is the origin of homochirality in the biosphere, that is, the fact that l-amino acids and d-sugars dominate in nature, while labo- ratory experiments produce a racemic mixture unless direct- ed by an added chiral source. [1, 2] Several mechanisms de- scribing how an initial imbalance between enantiomers might have come about, together with mechanisms for am- plifying this imbalance, have been proposed as an explana- tion for the origin of biomolecular single handedness. [3–12] Most prominent among these are far-from-equilibrium models that include stochastic symmetry breaking coupled with autocatalytic amplification associated with crystalliza- tion phenomena, such as Kondepudis “Eve crystal” model, [7] or chemical systems, such as the Soai reaction. [9] Recent intriguing experimental observations of the evolu- tion of solid-phase homochirality for mixtures of d and l crystals offer a new model that is distinct from these mecha- nisms, representing a near-equilibrium interplay between ki- netics and thermodynamics in a system that combines physi- cal phase behavior with chemical reaction processes. The original observations were made by Viedma, [11] who demon- strated that a racemic mixture of the two enantiomorphic crystals of the achiral salt NaClO 3 in equilibrium with its sa- turated solution is driven inexorably over time to a single chiral solid, aided by the energy input from abrasive grind- ing of the crystals. Simultaneously, but independently, Black- mond [13] and Viedma [14] suggested that this phenomenon could be extended to intrinsically chiral compounds that rac- emize in solution, and this proposal has since been verified experimentally for amino acid derivatives, [15] for the pro- teinogenic amino acid aspartic acid, [16] and for the amine product of a reversible Mannich reaction. [17] The mechanism of this remarkable process is still under vigorous discussion. [18–21] One of its most compelling features lies in a paradox: the key driving force for the evolution of Abstract: Solution-phase racemization drives the evolution of single chirality in the solid phase by the “chiral amne- sia” process first described by Viedma. The current investigations lay the basis for a better understanding of the mech- anism of the solid-phase deracemiza- tion by uncoupling the chemical rate processes associated with the intercon- version of enantiomers in the solution phase from the physical processes asso- ciated with solution–solid phase trans- fer via dissolution and reaccretion of molecules onto crystals. In addition, the enantiomer concentration profiles presented in this work, together with an analytical treatment of the racemi- zation process in the presence of excess enantiopure solid, unequivocally recon- firm the validity of the Meyerhoffer double solubility rule for systems under solution racemization conditions. Keywords: amino acids · chirality · deracemization · enantioenrich- ment · racemization [a] Prof. Dr. C. Viedma Departamento Cristalografia-Mineralogia, Facultad Geologia Universidad Complutense, 28040 Madrid (Spain) Fax: (+ 34) 91 3944872 E-mail: viedma@geo.ucm.es [b] B. J. V. Verkuijl, Prof. Dr. D. G. Blackmond Department of Chemistry Imperial College London, SW7 2AZ London (UK) [c] Prof. R. M. Kellogg Syncom B.V., Kadijk 3, 9747 AT Groningen (The Netherlands) Fax: (+ 31) 50 5757399 E-mail : r.m.kellogg@syncom.nl [d] J. E. Ortiz, T. de Torres Laboratorio de Estratigrafía Biomolecular EscuelaTØcnica Superior de Ingenieros de Minas de Madrid 28040 Madrid (Spain) [e] Prof. Dr. D. G. Blackmond Present address: Department of Chemistry The Scripps Research Institute La Jolla, CA 92037 (USA) Fax: (+ 1) 858 784 2180 E-mail: blackmond@scripps.edu  2010 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim Chem. Eur. J. 2010, 16, 4932 – 4937 4932