Orotic Acid in Water Solution, a DFT and ¹³C NMR Spectroscopic Study

Abstract

Orotic acid, a biologically important compound, can exist in aqueous solutions in several ionic and tautomeric forms. Interpretation of the experimental (13)C NMR chemical shifts of this compound based on the results of energy and magnetic shielding calculations performed by DFT B3LYP/6-311++G(2d,p)/PCM method has shown that in water solutions the diketo tautomers are the dominant structural forms of this acid and its anions. For neutral molecules the anti conformation is preferable, monoanion occurs as the conventional carboxylate anion, whereas the orotic dianion exists in two tautomeric forms in the proportion of ca. 4:1. It has been found that the experimental (13)C NMR chemical shifts can be reproduced well by the results of DFT calculations, although for the orotate monoanion some small but characteristic divergences can be noticed. Similar divergences have been also observed for a few other aromatic carboxylates. It seems that the specific solute-solvent interactions occurring in our systems can be the cause of this inconsistency. To support this hypothesis, a simple and effective method of including the specific hydration into the theoretical calculations has been proposed.

Orotic acid production by Yarrowia lipolytica under conditions of limited pyrimidine

“…In addition, NMR spectroscopy was used for a qualitative comparison of sample spectra (purified crude crystals) to a reference spectrum of commercially available OA (Figure 3). The 1 H 1D spectrum showed one proton signal (Figure 3a), and five carbon signals could be observed in the 13 C 1D experiment (Figure 3b), which is also described in the literature for the NMR spectroscopy of OA (Kubica & Gryff-Keller, 2015).…”

Electronic Structure, NMR, Spin–Spin Coupling, and Noncovalent Interactions in Aromatic Amino Acid Based Ionic Liquids

“…It has further been known that for noncovalently bonded systems the shielding constants and NMR parameters for example, indirect or direct nuclear SSCCs are critically dependent on the electronic structure and their computations requires good description of core as well as diffuse orbitals. − It should be remarked here that the density functional theoretic calculations incorporating the dispersion corrected M05-2x or related functionals combined with the Huzinaga and further extended correlated basis set have been carried out for water clusters and clatherates. , Deriving the electronic structure and NMR spectral characteristics with such level of theory becomes computationally demanding for large molecular systems. As an alternative, the M05-2x/6-311++G­(d,p) level of theory has widely been employed to derive the NMR parameters in the recent literature − and therefore the M05-2x/6-311++G­(d,p) approach has been identified to be economical and convenient in terms of quality to cost ratio for obtaining NMR chemical shifts. We therefore employ this level of theory for deriving NMR characteristics of aromatic AAILs studied in this work.…”

“…The accurate determination of NMR parameters is a challenging task and requires simulation of electron correlation and extended basis set. 71 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 employed to derive the NMR parameters in the recent literature [78][79][80][81][82][83][84][85] and accordingly the M05-2x/6-311++G(d,p) approach has been identified to be economical and convenient in terms of quality to cost ratio for obtaining the NMR chemical shifts. We therefore employ this level of theory for deriving NMR characteristics of aromatic AAILs studied in this work.…”

Recent Advances in Theoretical and Physical Aspects of NMR Chemical Shifts

“…Non-relativistic DFT calculations of shielding for light atoms, usually with PCM standing in for the solvent, provide quick resolution of spectral assignments and answers to structural questions for experimentalists. Some recent examples are the following: DFT calculation of 15 N NMR chemical shifts of the nitrogencontaining heterocycles (best results with KT3 functional) (Samultsev et al, 2014), using the KT3 functional and PCM for 15 N NMR chemical shifts of 27 azoles and azines in 10 different solvents (Semenov et al, 2014), using mPW1PW91 functional for calculations of 1 H chemical shifts in lactones (Aimola et al, 2015), using B3LYP for 1 H and 13 C in tautomeric 1-[(pyridin-2-yl amino) methyl] pyrrolidine-2,5-dione (Boobalan et al, 2014), using mPW1PW91 and PCM for 1 H and 13 C in lignin amino acid adducts (Diehl et al, 2014), using 16 different functionals for 1 H and 13 C in (R)-ispinesib, a drug molecule (Hill et al, 2015), using B3LYP in COSMO solvent model for for 1 H and 13 C shielding in bis(4trimethylammoniumbenzoate) hydroiodide hydrate in DMSO (Komasa et al, 2015), using B3LYP for 13 C shielding in tautomers of vitamin B-13 in PCM solvent model (Kubica and Gryff-Keller, 2015), using 7 different functionals for 13 C shielding in 2hydroxylamino-4,6-dinitrotoluene (Liu et al, 2015), using BP86 functional for 13 C shielding tensors in C60 and C60 10+ (Munoz-Castro, 2015), using BHandH functional for 13 C and 17 O in 1,3-dioxolane and 19 F in perfluoro-1,3dioxolane (Nozirov et al, 2014), using B3LYP for 1 H and 13 C in in 2-bromo-1H-benzimidazol (Sas et al, 2015), using B3LYP for 1 H and 13 C shielding in 1:2 complex of dimethylphenyl betaine with 2,6-dichloro-4nitro-phenol in DMSO (Szafran et al, 2015), and using the MPW1K (Lynch et al, 2000) hybrid functional with PCM solvent model for 29 Si in 24 organosilanes (Zhang et al, 2014 parameters, nuclear shielding in particular, has appeared (Bagno and Saielli, 2015).…”