Stabilization of zwitterionic proline by DMSO

Zwitterionic stabilization and metal‐free organocatalysis are two emerging topics. In this work, the numbers of DMSO molecules required to render zwitterionic proline geometrically stable, energetically preferential, and conformationally predominant have been determined, as one, three, and three, respectively. Conformations are analyzed for proline conformers interacted with one, two, and three DMSO molecules, and three DMSO molecules are enough to fill up the first shell of proline. Relative stabilities of two selected canonical structures are dependent on the DMSO contents, while zwitterionic stabilities improve monotonously with increase of DMSO contents. DMSO causes a conformational diversity and good zwitterionic stabilization effects, which result from the synergetic effects of two types of H‐bonding interactions. With increase of DMSO contents, type‐2 H‐bonding (CH as donors) contributes more to zwitterionic stabilization. At any DMSO content, zwitterionic proline is facile to form because of low activation energies, and this study helps to understand proline‐catalyzed processes. © 2015 Wiley Periodicals, Inc.