Lewis acidity is customarily gauged by comparing the relative magnitude of coordinate covalent bonding energies, where the Lewis acid moiety is varied and the Lewis base is kept constant. However, the prediction of Lewis acidity from first principles is sometimes contrary to that suggested by experimental bond energies. Specifically, the order of boron trihalide Lewis acidities predicted from substituent electronegativity arguments is opposite to that inferred by experiment. Contemporary explanations for the divergence between theory, computation, and experiment have led to further consternation. Due to the fundamental importance of understanding the origin of Lewis acidity, we report periodic trends for 21 boron Lewis acids, as well as their coordinate covalent bond strengths with NH3, utilizing ab initio, density functional theory, and natural bond orbital analysis. Coordinate covalent bond dissociation energy has been determined to be an inadequate index of Lewis acid strength. Instead, acidity is measured in the manner originally intended by Lewis, which is defined by the valence of the acid of interest. Boron Lewis acidity is found to depend upon substituent electronegativity and atomic size, differently than for known Brønsted−Lowry periodic trends. Across the second period, stronger substituent electronegativity correlates (R2 = 0.94) with increased Lewis acidity. However, across the third period, an equal contribution from substituent electronegativity and atomic radii is correlated (R2 = 0.98) with Lewis acidity. The data suggest that Lewis acidity depends upon electronegativity solely down group 14, while equal contribution from both substituent electronegativity and atomic size are significant down groups 16 and 17. Originally deduced from Pauling’s electronegativities, boron’s substituents determine acidity by influencing the population of its valence by withdrawing electron density. However, size effects manifest differently than previously considered, where greater σ bond (not π bond) orbital overlap between boron and larger substituents increase the electron density available to boron’s valence, thereby decreasing Lewis acidity. The computed electronegativity and size effects of substituents establish unique periodic trends that provide a novel explanation of boron Lewis acidity, consistent with first principle predictions. The findings resolve ambiguities between theory, computation, and experiment and provide a clearer understanding of Lewis acidity.

Truhlar’s new generation of hybrid meta-generalized gradient functionals has been evaluated in modeling the binding enthalpies of substituted B−N coordinate covalent bonds. The short-range exchange correlation (XC) energy of coordinate covalent bonding coupled with the medium-range XC energy of noncovalent interactions results in a particularly difficult case for density functional theory (DFT). In this study, M06, M06−2X, M05, M05−2X, MPWB1K, and MPW1B95 with the 6−311++G(3df,2p) basis set have been used to evaluate four methylated ammonia trimethylboranes, (CH3)3B−N(CH3)nH3-n (n = 0 to 3), along with H3B-NH3. The predicted binding enthalpies from the new functionals have been compared to experiment as well as previous DFT (B3LYP, MPW1K) and ab initio (HF, MP2, QCISD, and QCISD(T)) results. Previously, only MP2, QCISD, and QCISD(T) were found to model the experimental energetic trend accurately. The mean absolute deviation (MAD) from experimental binding enthalpies for M06−2X and M05−2X is 0.3 and 1.6 kcal/mol, respectively. M06−2X yields a lower MAD than more expensive ab initio methods (MP2 = 1.9 kcal/mol and QCISD = 2.3 kcal/mol) and a comparable MAD to QCISD(T) (MAD = 0.4 kcal/mol). M06−2X is shown to provide a balanced account of the short- and medium-range XC energies necessary to describe the binding enthalpy of coordinate covalent bonds accurately in sterically congested molecular systems.

The utility of multiple trajectories to extend the time scale of molecular dynamics simulations is reported for the spectroscopic A-states of carbonmonoxy myoglobin (MbCO). Experimentally, the A0→A1–3 transition has been observed to be 10 μs at 300 K, which is beyond the time scale of standard molecular dynamics simulations. To simulate this transition, 10 short (400 ps) and two longer time (1.2 ns) molecular dynamics trajectories, starting from five different crystallographic and solution phase structures with random initial velocities centered in a 37 Å radius sphere of water, have been used to sample the native-fold of MbCO. Analysis of the ensemble of structures gathered over the cumulative 5.6 ns reveals two biomolecular motions involving the side chains of His64 and Arg45 to explain the spectroscopic states of MbCO. The 10 μs A0→A1–3 transition involves the motion of His64, where distance between His64 and CO is found to vary up to 8.8±1.0 Å during the transition of His64 from the ligand (A1–3) to bulk solvent (A0). The His64 motion occurs within a single trajectory only once, however the multiple trajectories populate the spectroscopic A-states fully. Consequently, multiple independent molecular dynamics simulations have been found to extend biomolecular motion from 5 ns of total simulation to experimental phenomena on the microsecond time scale.