Refined Structures of -Phospho-l-serine and Its Calcium Salt by New Multinuclear Solid-State NMR Crystallography Methods.

-phospho-l-serine (Pser) and its Ca salt, Ca[-phospho-l-serine]·HO (CaPser), play important roles for bone mineralization and were recently also proposed to account for the markedly improved bone-adhesive properties of Pser-doped calcium phosphate-based cements for biomedical implants. However, the hitherto few proposed structural models of Pser and CaPser were obtained by X-ray diffraction, thereby leaving the proton positions poorly defined. Herein, we refine the Pser and CaPser structures by density functional theory (DFT) calculations and contrast them with direct interatomic-distance constraints from two-dimensional (2D) nuclear magnetic resonance (NMR) correlation experimentation at fast magic-angle spinning (MAS), encompassing double-quantum-single-quantum (2Q-1Q) H NMR along with heteronuclear C{H} and P{H} correlation NMR experiments. The Pser and CaPser structures before and after refinements by DFT were validated against sets of NMR-derived effective H-H, H-P, and H-C distances, which confirmed the improved accuracy of the refined structures. Each distance set was derived from one sole 2D NMR experiment applied to a powder without isotopic enrichment. The distances were extracted without invoking numerical spin-dynamics simulations or approximate phenomenological models. We highlight the advantages and limitations of the new distance-extraction procedure. Isotropic H, C, and P chemical shifts obtained by DFT calculations using the gauge including projector augmented wave (GIPAW) method agreed very well with the experimental results. We discuss the isotropic and anisotropic C and P chemical-shift parameters in relation to the previous literature, where most data on CaPser are reported herein for the first time.