Condensation dynamics of L-proline and L- hydroxyproline in solution Mieczyslaw Sajewicz, a Milo ˇ s Dolnik, b Teresa Kowalska a and Irving R. Epstein * b We employ high-performance liquid chromatography with evaporative light scattering and mass spectrometric detection (HPLC/ELSD and LC/MS) to monitor the dynamic behavior of L-Pro, L-Hyp, and L-Pro–L-Hyp in 70% aqueous methanol. The individual amino acid solutions show evidence of oscillatory oligomerization. In the binary solution, the behavior is controlled by the dynamics of L-Pro oligomerization. A simple model involving oligomerization, formation of catalytic oligomer aggregates and cross-catalysis provides qualitative insight into the process. Introduction Spontaneous chiral inversion of nonsteroidal anti-inamma- tory drugs (NSAIDs) in living organisms and in tissue culture has been studied for nearly half a century. 1 In vitro evidence that this process can proceed in an oscillatory fashion in low molecular weight carboxylic acids dissolved in aqueous and non-aqueous abiotic media was rst obtained in profen drugs, 2 a class of NSAIDs. Later, the phenomenon was shown to be quite general, occurring in chiral derivatives of acetic, propionic, and butyric acids with a chiral center located either on the a- or the b-carbon atom (e.g., ref. 3). Subsequent work found that oscillatory chiral conversion can be accompanied by oscillatory oligomerization. The ability of amino acids to undergo spontaneous peptid- ization in aqueous solution was rst demonstrated by means of the biuret test with L-phenylglycine. 4 Several other amino acids were investigated with high performance liquid chromatog- raphy accompanied by diode array and mass spectrometric detection (e.g., ref. 5). A general scheme for chiral conversion of low molecular weight carboxylic acids in aqueous solution can be represented as: 6 (1) where X: –R (aliphatic) and Y: –NH 2 , –OH, or –Ar (aromatic). In anhydrous media and in the presence of trace amounts of water, the probable mechanism of chiral conversion is: 7 (2) In amino acids, the parallel processes of chiral conversion and peptidization can be illustrated by the following scheme: 8 (3) In this study, we present the results of experiments with L-proline (L-Pro) and L-hydroxyproline (L-Hyp), two important endogenous amino acids, both of which contain a ve-membered pyrrolidine ring, as shown below. We selected these two amino acids because of their important role as building blocks of collagen, which is omnipresent in the connective tissue of mammals and largely responsible for tissue architecture and strength. More specically, our interest in struc- tural transformations of these amino acids was attracted by the reluctance of L-Pro to participate in alpha helices 9,10 and to the frequent presence of L-Pro and L-Hyp in the collagen triple helix. 11,12 a Institute of Chemistry, University of Silesia, 9 Szkolna Street, 40-006 Katowice, Poland b Department of Chemistry, Brandeis University, MS 015, Waltham, MA 02454-9110, USA. E-mail: epstein@brandeis.edu Cite this: RSC Adv. , 2014, 4, 7330 Received 21st November 2013 Accepted 4th January 2014 DOI: 10.1039/c3ra46921b www.rsc.org/advances 7330 | RSC Adv., 2014, 4, 7330–7339 This journal is © The Royal Society of Chemistry 2014 RSC Advances PAPER