Palascak and Shields 1 claim to have derived accurate experimental values for the hydration free energies of H + , OH -, and H 3 O + . The purpose of this Comment is to alert the community that, in fact, their values are less accurate than the values they are meant to replace. In what follows we show the errors Palascak and Shields made and, by example, give practical advice on how to ensure correct assignment of standard states for reactions with water as a reactant or product in gas and solution phases.Palascak and Shields begin the derivation of hydration free energies of OHand H 3 O + by asserting that the most reliable estimate of the experimental value for hydration of a proton is -264 kcal/mol. 2,3 They use this value as if the reference standard states are 1 M for both gas and aqueous phases, i.e., ∆ s G*(H + ). 4,5 This practice is wrong. Tissander et al. 2 and Tuttle et al. 3 derive the hydration free energy of a proton by correlating ion-water cluster data, referenced to standard gas phase conditions (1 bar, 298 K), with free energies of hydration of the anion-cation pairs that are derived from gas phase reaction energies referenced to the 1-bar standard state and aqueous reactions referenced to 1-m standard state. Therefore, the recommended value (-264 kcal/mol) for the hydration of a proton represents the conventional process with standard states essentially equal to 1 atm for gas and 1 M for solution. To convert from the 1-atm gas phase/1-m solution standard state to the 1-M gas/ 1-M solution standard state, one must subtract 1.9 kcal/mol, 6 such that ∆ s G*(H + ) ) -265.9 kcal/mol. 7,8 Bartels and coworkers 9 have recently reproduced this result to within 0.2 kcal/ mol and derived values for temperatures up to 648 K using the SUPCRT92 software package. 10 Solvation energies of ions based on ∆ s G*(H + ) ) -265.9 kcal/mol have been widely adopted. 11 This benchmark experimental value should not be changed unless/until it is superseded by better measurements. [12][13][14] Accordingly, Palascak's and Shields' determination of ∆ s G*(OH -) is too negative by 1.9 kcal/mol. With this correction, the value is ∆ s G*(OH -) ) -104.5 kcal/mol, which is in good agreement with the value previously determined by Pliego and Riveros. 15 Not converting ∆ s G°(H + ) to number density standard states is just one of the problems with Palascak's and Shields' paper. A more serious problem arises in the derivation by Palascak and Shields of the hydration free energy of H 3 O + . Their value is several kcal/mol less negative than the value previously

Photoinduced concerted electron-proton transfer (EPT), denoted photo-EPT, is important for a wide range of energy conversion processes. Transient absorption and Raman spectroscopy experiments on the hydrogen-bonded p-nitrophenylphenol-t-butylamine complex, solvated in 1,2-dichloroethane, suggested that this complex may undergo photo-EPT. The experiments probed two excited electronic states that were interpreted as an intramolecular charge transfer (ICT) state and an EPT state. Herein mixed quantum mechanical/molecular mechanical nonadiabatic surface hopping dynamics is used to investigate the relaxation pathways following photoexcitation. The potential energy surface is generated on the fly with a semiempirical floating occupation molecular orbital complete active space configuration interaction method for the solute molecule and a molecular mechanical force field for the explicit solvent molecules. The free energy curves along the proton transfer coordinate illustrate that proton transfer is thermodynamically and kinetically favorable on the lower-energy excited state but not on the higher-energy excited state, supporting the characterization of these states as EPT and ICT, respectively. The nonadiabatic dynamics simulations indicate that the population decays from the ICT state to the EPT state in ∼100 fs and from the EPT state to the ground state on the slower time scale of ∼1 ps, qualitatively consistent with the experimental measurements. For ∼54% of the trajectories, the proton transfers from the phenol to the amine in ∼400 fs on the EPT state and then transfers back to the phenol rapidly upon decay to the ground state. Thus, these calculations augment the original interpretation of the experimental data by providing evidence of proton transfer on the EPT state prior to decay to the ground state. The fundamental insights obtained from these simulations are also relevant to other photo-EPT processes.

We report the design, synthesis and testing of a series of novel bisphosphonates, pyridinium-1-yl-hydroxy-bisphosphonates, based on the results of comparative molecular similarity indices analysis and pharmacophore modeling studies of farnesyl diphosphate synthase (FPPS) inhibition, human Vgamma2Vdelta2 T cell activation and bone resorption inhibition. The most potent molecules have high activity against an expressed FPPS from Leishmania major, in Dictyostelium discoideum growth inhibition, in gammadelta T cell activation and in an in vitro bone resorption assay. As such, they represent useful new leads for the discovery of new bone resorption, antiinfective and anticancer drugs.