The pKa value of the alpha-phosphate moiety of uridine 5'-diphosphate-GIcNAc (UDP-GIcNAc) has been successfully calculated using density functional theory methods in conjunction with the Polarizable Continuum Models. Theoretical methods were benchmarked over a dataset comprising of alkyl phosphates. B3LYP/6-31+G(d,p) calculations using SMD solvation model provide excellent agreement with the experimental data. The predicted pKa for UDP-GIcNAc is consistent with most recent NMR studies but much higher than what it has long been thought to be. The importance of this study is evident that the predicted pKa for UDP-GIcNAc supports its potential role as a catalytic base in the substrate-assisted biocatalysis. (C) 2016 Elsevier B.V. All rights reserved.