Molecular origin of 31P-NMR chemical shifts of phosphate groups with bivalent counter ions

TL;DR

This study combines experimental NMR and computational simulations to elucidate how bivalent counter ions like Mg2+ and Ca2+ influence the 31P chemical shifts in phosphate groups, revealing microscopic mechanisms and ion pairing effects.

Contribution

It provides a detailed microscopic understanding of phosphate-ion interactions affecting 31P-NMR shifts, integrating experimental data with advanced simulations to improve force field accuracy.

Findings

Contact ion pairs cause a 3-5 ppm shift in 31P chemical shifts.

Solvent-separated ion pairs are energetically favored over contact pairs.

Temperature-dependent analysis reveals the fraction of ion pairing species.

Abstract

The electrostatic interactions of phosphate groups and counter ions critically affect the structure, function and reactivity of DNA or RNA. We present a joint experimental-theoretical investigation of dimethyl phosphate (DMP-) in aqueous solution, an established model system of the sugar-phosphate backbone. Utilizing 31P-NMR spectroscopy as probe of phosphate-ion association, variations of Mg2+ and Ca2+ content exhibit a systematic shielding of the 31P chemical shift ({\delta}iso(31P)) with moderate temperature dependence. Enhanced sampling molecular dynamics (MD) and ab initio (GIAO-DF-LMP2) level of theory are used to reveal the microscopic mechanism. Simulations are performed for a configurational ensemble of DMP-ion geometries and their first solvation shells, demonstrating (i) the spatial convergence of changes of the nuclear shielding constant {\sigma}iso(31P), (ii) the intramolecular geometric origin of short-timescale {\sigma}iso(31P) fluctuations and (iii) an average shift of {\sigma}iso(31P) of about 3-5 ppm upon contact ion pair formation with Mg2+ or Ca2+ ions. A quantitative analysis of {\delta}iso(31P) for varying ion content and temperature allows us to extract the temperature-dependent fraction of the contact ion pair species, indicating that solvent separated or free ion pairs are the energetically preferred species. The results impose boundary conditions for improvements of phosphate ion force fields and establish the interactions underlying the changes of {\delta}iso(31P).