Assessment of density functionals, semiempirical methods, and SCC-DFTB for protonated creatinine geometries

Creatinine concentrations in blood and urine can be used to detect renal insufficiencies and muscle diseases, but current chemical sensors cannot measure creatinine with sufficient selectivity and robustness because they lack a receptor that binds protonated creatinine (creatininium) selectively enough. As a first step toward identifying potential receptors for creatininium, we examine the accuracy of density functional theory (DFT) and wave function theory (WFT) calculations for creatininium cation geometries, evaluated against reference parameters from experiment. We tested twenty-one local and nonlocal density functionals, Hartree-Fock theory, four semiempirical molecular orbital (SEMO) methods of the neglect of differential overlap (NDO) type, and one self-consistent-field nonorthogonal tight-binding method (SCC-DFTB) as implemented in two closely related software packages. DFT and HF calculations were carried out with the MG3S augmented polarized triple-zeta basis set. We find that DFT significantly outperforms SEMO methods for our dataset, and both SCC-DFTB releases we tested (which gave almost identical results) were less accurate than 81% of the density functionals evaluated. The top five functionals for the creatininium structures we examined were MPW1B95, PBEh, mPW1PW, SVWN5, and B97-2, with MMUEs in bond length of 0.0126, 0.0129, 0.0133, 0.0142, and 0.0144 Å respectively, which indicates that all five functionals are similarly suitable for creatininium. The popular B3LYP functional has a MMUE of 0.0178 Å, which ranks it 16th overall. B3LYP also performs less favorably than the best local functional (SVWN5), which is less expensive.