title: Phosphorylation as a method of tuning the enantiodiscrimination potency of quinine--an NMR study.
abstract: Quinines phosphorylated at the C-9 hydroxyl group (diphenyl and diethyl phosphates) were synthesized and validated as novel effective chiral solvating agents in two alternative methods based on (1)H and (31)P NMR spectroscopy. Tested with a representative set of racemic analytes, the title compounds induced shift nonequivalence effects in (1)H NMR signals with values up to 0.1-0.2 ppm for 3,5-dinitrobenzoyl-substituted amino acids. In terms of enantiodifferentiation extent and application range, introduction of a phosphate group was proven to be superior compared to the action of nonmodified quinine. Interestingly, a temperature decrease to reach the slow exchange conditions also produced nonequivalences in the (31)P NMR spectra of the selectors. Comprehensive NMR analysis showed the existence of two conformations (closed 1 and 2) for both quinines in their free forms and the open 3 arrangement for the protonated ones. The crystal structure of diethylphosphorylquinine hydrochloride dichloromethane hemisolvate revealed a similar conformation to that observed in solution. Structures of complexes of phosphorylated quinines with selected ligands were determined with the use of NMR-based molecular modeling studies.
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wrocław, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Górecki
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Berlicki
authors.forename: Artur
authors.initials: A
authors.lastname: Mucha
authors.forename: Paweł
authors.initials: P
authors.lastname: Kafarski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Ślepokura
authors.forename: Ewa
authors.initials: E
authors.lastname: Rudzińska-Szostak
mesh_terms: D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D010766:Phosphorylation; D011522:Protons; D011803:Quinine / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D011522:Protons; D011803:Quinine