(4R)-4-Hydroxy-1-nitroso-l-proline: synthesis, X-ray structure, ab initio and conformational calculations

Abstract: 4-Hydroxy-l-proline, an amino acid, an important component of collagen, was transformed into its N-nitroso-derivative, (4R)-4-hydroxy-1-nitroso-l-proline, 1 by butylnitrite in the acidic medium. The structure is a cyclic hydroxy-N-nitrosoacid with the carboxyl and hydroxyl groups trans to each other. The carboxyl group is in the syn-conformation. In the structure, the neutral molecules are connected via classical intermolecular O–H⋯O hydrogen bonds involving the hydroxyl and carboxyl groups [O⋯O=2.6251(14)Å], and form chains along the a-axis direction. The chains are linked into sheets via O–H⋯O hydrogen bond, [O⋯O=2.6813(15)Å] with participation of oxygen atom of nitroso group. Ab initio calculations based on density functional theory at the B3LYP/6-311++G(d, p) level of theory were performed to analyze the influence of 4-hydroxy-l-proline (Hyp) nitrosation on the conformation of the synthesized N-nitroso-compound. The geometry optimization of 1 and initial 4-hydroxy-l-proline was carried out in the gas phase and in solution using the polarizable continuum model. The single-point calculation was performed for the crystal structure of 1. The most stable conformer of 1 is observed in an aqueous solution. In this state, the pyrrolidine ring adopts an envelope conformation, which is also maintained in the gas phase. The twisted conformation of the pyrrolidine ring is present in all states of Hyp and in the crystal structure of 1. In 1 the interchange of five-membered ring conformation in solution and in the gas phase in comparison with the crystal is accompanied by an increase of the dipole moment of the molecule, which is maximal in solution. [Copyright &y& Elsevier]