Hydration properties of aqueous Pb(II) ion

Using density functional theory and polarized continuum models, we have determined the most probable coordination number and structure of the first hydration shell of aqueous Pb(II). The geometries and hydration free energies of Pb(H2O)(1-9)(2+) were examined and benchmarked against experimental values. The free energies of hydration of Pb(H2O)(6-8)(2+) were found to match the experimental value within 10 kcal/mol. Moreover, based upon our thermochemical results for single water addition, primary hydration numbers of 6, 7, and 8 are all thermally accessible at STP. Use of a small-core 60 electron effective core potential (ECP) with the aug-cc-pvdz-PP basis on Pb resulted in structures that are significantly less hemidirected than predicted when using the large-core 78 electron ECP and the lanl2DZ basis on the metal. Our results imply that the hemi- to holo-directed transition in Pb(II)-water complexes is driven by coordination number and not hybridization of the 6s lone-pair orbital or enhanced covalent bonding in the Pb-OH2 bond. In addition to basis set effects, the influence of different solvation models on hydration reactions has further been examined so as to determine the relative accuracy of the calculated hydration thermochemistry.     

Charge‐Shift Bonding: A New and Unique Form of Bonding

Charge‐shift bonds (CSBs) constitute a new class of bonds different than covalent/polar‐covalent and ionic bonds. Bonding in CSBs does not arise from either the covalent or the ionic structures of the bond, but rather from the resonance interaction between the structures. This Essay describes the reasons why the CSB family was overlooked by valence‐bond pioneers and then demonstrates that the unique status of CSBs is not theory‐dependent. Thus, valence bond (VB), molecular orbital (MO), and energy decomposition analysis (EDA), as well as a variety of electron density theories all show the distinction of CSBs vis‐à‐vis covalent and ionic bonds. Furthermore, the covalent–ionic resonance energy can be quantified from experiment, and hence has the same essential status as resonance energies of organic molecules, e.g., benzene. The Essay ends by arguing that CSBs are a distinct family of bonding, with a potential to bring about a Renaissance in the mental map of the chemical bond, and to contribute to productive chemical diversity.     

Comparison of two simulation methods to compute solvation free energies and partition coefficients

The thermodynamic integration (TI) and expanded ensemble (EE) methods are used here to calculate the hydration free energy in water, the solvation free energy in 1‐octanol, and the octanol‐water partition coefficient for a six compounds of varying functionality using the optimized potentials for liquid simulations (OPLS) all‐atom (AA) force field parameters and atomic charges. Both methods use the molecular dynamics algorithm as a primary component of the simulation protocol, and both have found wide applications in fields such as the calculation of activity coefficients, phase behavior, and partition coefficients. Both methods result in solvation free energies and 1‐octanol/water partition coefficients with average absolute deviations (AAD) from experimental data to within 4 kJ/mol and 0.5 log units, respectively. Here, we find that in simulations the OPLS‐AA force field parameters (with fixed charges) can reproduce solvation free energies of solutes in 1‐octanol with AAD of about half that for the solute hydration free energies using a extended simple point charge (SPC/E) model of water. The computational efficiency of the two simulation methods are compared based on the time (in nanoseconds) required to obtain similar standard deviations in the solvation free energies and 1‐octanol/water partition coefficients. By this analysis, the EE method is found to be a factor of nine more efficient than the TI algorithm. For both methods, solvation free energy calculations in 1‐octanol consume roughly an order of magnitude more CPU hours than the hydration free energy calculations. © 2012 Wiley Periodicals, Inc.     

Box size effects are negligible for solvation free energies of neutral solutes

Hydration free energy calculations in explicit solvent have become an integral part of binding free energy calculations and a valuable test of force fields. Most of these simulations follow the conventional norm of keeping edge length of the periodic solvent box larger than twice the Lennard-Jones (LJ) cutoff distance, with the rationale that this should be sufficient to keep the interactions between copies of the solute to a minimum. However, for charged solutes, hydration free energies can exhibit substantial box size-dependence even at typical box sizes. Here, we examine whether similar size-dependence affects hydration of neutral molecules. Thus, we focused on two strongly polar molecules with large dipole moments, where any size-dependence should be most pronounced, and determined how their hydration free energies vary as a function of simulation box size. In addition to testing a variety of simulation box sizes, we also tested two LJ cut-off distances, 0.65 and 1.0 nm. We show from these simulations that the calculated hydration free energy is independent of the box-size as well as the LJ cut-off distance, suggesting that typical hydration free energy calculations of neutral compounds indeed need not be particularly concerned with finite-size effects as long as standard good practices are followed.     

Treating entropy and conformational changes in implicit solvent simulations of small molecules

Implicit solvent models are increasingly popular for estimating aqueous solvation (hydration) free energies in molecular simulations and other applications. In many cases, parameters for these models are derived to reproduce experimental values for small molecule hydration free energies. Often, these hydration free energies are computed for a single solute conformation, neglecting solute conformational changes upon solvation. Here, we incorporate these effects using alchemical free energy methods. We find significant errors when hydration free energies are estimated using only a single solute conformation, even for relatively small, simple, rigid solutes. For example, we find conformational entropy (TDeltaS) changes of up to 2.3 kcal/mol upon hydration. Interestingly, these changes in conformational entropy correlate poorly (R2 = 0.03) with the number of rotatable bonds. The present study illustrates that implicit solvent modeling can be improved by eliminating the approximation that solutes are rigid.     

Bonding analysis for NgAuOH (Ng = Kr,Xe)

Noble‐gas‐noble‐metal hydroxides NgAuOH (Ng = Kr, Xe) are investigated at the MP2 theoretical level. All species are found to be in Cs symmetry with an approximate linear Ng? Au? O moiety. The noble‐gas‐noble‐metal bond lengths are comparable with covalent limits, and the corresponding binding energies have been computed to be 59.6 and 83.4 kJ/mol for KrAuOH and XeAuOH, respectively. Except the charge‐induced dipole contribution to the binding energies, the remainder could be ascribed to the higher‐order charge‐induction energies, dispersion energies, the contributions of multipole moments on AuOH and covalent effects. The title species are sufficiently chemical bound and are expected to be stable species theoretically. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008     

Evaluating the relative free energy of hydration of new thrombin inhibitor candidates using the finite difference thermodynamic integration (FDTI) method

Thrombin is a serine protease involved in blood coagulation. Since thrombin inhibitors appear to be effective in the treatment and prevention of thrombotic and embolic disorders, considerable attention has been focused on the structure and interactions of the enzyme. In this work, we calculated the relative free energies of hydration of the new thrombin inhibitor candidates, p‐substituted derivatives of benzamidine, a well‐known noncovalent thrombin inhibitor. We used molecular dynamics and the finite difference thermodynamic integration (FDTI) algorithm within the Discover program of MSI. We have shown that the orthogonality problem that occurs in the calculation of intraperturbed‐group contributions to the free energy is treated adequately by the FDTI method. We have also shown that problems of singularity and convergence in free energy calculations can be properly solved using this method. To conclude, the calculated free energies of hydration gave the following order of solvation for the candidates: p‐(2‐oxo‐1‐propyl)benzamidine > p‐methylbenzamidine > p‐ethylbenzamidine > p‐(1‐propyl)benzamidine > benzamidine. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001     

Blind prediction of solvation free energies from the SAMPL4 challenge

Here, we give an overview of the small molecule hydration portion of the SAMPL4 challenge, which focused on predicting hydration free energies for a series of 47 small molecules. These gas-to-water transfer free energies have in the past proven a valuable test of a variety of computational methods and force fields. Here, in contrast to some previous SAMPL challenges, we find a relatively wide range of methods perform quite well on this test set, with RMS errors in the 1.2 kcal/mol range for several of the best performing methods. Top-performers included a quantum mechanical approach with continuum solvent models and functional group corrections, alchemical molecular dynamics simulations with a classical all-atom force field, and a single-conformation Poisson–Boltzmann approach. While 1.2 kcal/mol is still a significant error, experimental hydration free energies covered a range of nearly 20 kcal/mol, so methods typically showed substantial predictive power. Here, a substantial new focus was on evaluation of error estimates, as predicting when a computational prediction is reliable versus unreliable has considerable practical value. We found, however, that in many cases errors are substantially underestimated, and that typically little effort has been invested in estimating likely error. We believe this is an important area for further research.     

Extended solvent-contact model approach to SAMPL4 blind prediction challenge for hydration free energies

Extended solvent-contact model was applied to the blind prediction of the hydration free energies of 47 organic molecules included in the SAMPL4 data set. To obtain a suitable prediction tool, we constructed a hydration free energy function involving three kinds of atomic parameters. With respect to total 34 atom types introduced to describe all SAMPL4 molecules, 102 atomic parameters were defined and optimized with a standard genetic algorithm in such a way to minimize the difference between the experimental hydration free energies and those calculated with the hydration free energy function. In this parameterization, we used a training set comprising 77 organic molecules with varying sizes and shapes. The estimated hydration free energies for the SAMPL4 molecules compared reasonably well with the experimental results with the associated squared correlation coefficient and root mean square deviation of 0.89 and 1.46 kcal/mol, respectively. Based on the comparative analysis of experimental and computational hydration free energies of the SAMPL4 molecules, the methods for further improvement of the present hydration model are suggested.     

"Covalent hydration" reactions in model monomeric Ru 2,2'-bipyridine complexes: thermodynamic favorability as a function of metal oxidation and overall spin states

Density functional theory (DFT) has been used to investigate the plausibility of water addition to the simple mononuclear ruthenium complexes, [(NH(3))(3)(bpy)Ru═O](2+/3+) and [(NH(3))(3)(bpy)RuOH](3+), in which the OH fragment adds to the 2,2'-bipyridine (bpy) ligand. Activation of bpy toward water addition has frequently been postulated within the literature, although there exists little definitive experimental evidence for this type of "covalent hydration". In this study, we examine the energetic dependence of the reaction upon metal oxidation state, overall spin state of the complex, as well as selectivity for various positions on the bipyridine ring. The thermodynamic favorability is found to be highly dependent upon all three parameters, with free energies of reaction that span favorable and unfavorable regimes. Aqueous addition to [(NH(3))(3)(bpy)Ru═O](3+) was found to be highly favorable for the S = 1/2 state, while reduction of the formal oxidation state on the metal center makes the reaction highly unfavorable. Examination of both facial and meridional isomers reveals that when bipyridine occupies the position trans to the ruthenyl oxo atom, reactivity toward OH addition decreases and the site preferences are altered. The electronic structure and spectroscopic signatures (EPR parameters and simulated spectra) have been determined to aid in recognition of "covalent hydration" in experimental systems. EPR parameters are found to uniquely characterize the position of the OH addition to the bpy as well as the overall spin state of the system.     

Covalent Inter‐Carbon‐Allotrope Architectures Consisting of the Endohedral Fullerene Sc3N@C80 and Single‐Walled Carbon Nanotubes

Using a reductive sidewall functionalization concept, we prepared for the first time a covalent inter‐carbon‐allotrope hybrid consisting of single‐walled carbon nanotubes (SWCNTs) and the endohedral fullerene Sc₃N@C₈₀. The new compound type was characterized through a variety of techniques including absorption spectroscopy, Raman spectroscopy, TG‐MS, TG‐GC‐MS, and MALDI‐TOF MS. HRTEM investigations were carried out to visualize this highly integrated architecture.     

Theoretical studies on the effects of methods and parameterization on the calculated free energy of hydration for small molecules

Free energies of hydration (FEH) have been computed for 13 neutral and nine ionic species as a difference of theoretically calculated Gibbs free energies in solution and in the gas phase. In‐solution calculations have been performed using both SCIPCM and PCM polarizable continuum models at the density functional theory (DFT)/B3LYP and ab initio Hartree–Fock levels with two basis sets (6‐31G* and 6‐311++G**). Good linear correlation has been obtained for calculated and experimental gas‐phase dipole moments, with an increase by ～30% upon solvation due to solute polarization. The geometry distortion in solution turns out to be small, whereas solute polarization energies are up to 3 kcal/mol for neutral molecules. Calculation of free energies of hydration with PCM provides a balanced set of values with 6‐31G* and 6‐311++G** basis sets for neutral molecules and ionic species, respectively. Explicit solvent calculations within Monte Carlo simulations applying free energy perturbation methods have been considered for 12 neutral molecules. Four different partial atomic charge sets have been studied, obtained by a fit to the gas‐phase and in‐solution molecular electrostatic potentials at in‐solution optimized geometries. Calculated FEH values depend on the charge set and the atom model used. Results indicate a preference for the all‐atom model and partial charges obtained by a fit to the molecular electrostatic potential of the solute computed at the SCIPCM/B3LYP/6‐31G* level. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004     

Assessing the quality of absolute hydration free energies among CHARMM‐compatible ligand parameterization schemes

Multipurpose atom‐typer for CHARMM (MATCH), an atom‐typing toolset for molecular mechanics force fields, was recently developed in our laboratory. Here, we assess the ability of MATCH‐generated parameters and partial atomic charges to reproduce experimental absolute hydration free energies for a series of 457 small neutral molecules in GBMV2, Generalized Born with a smooth SWitching (GBSW), and fast analytical continuum treatment of solvation (FACTS) implicit solvent models. The quality of hydration free energies associated with small molecule parameters obtained from ParamChem, SwissParam, and Antechamber are compared. Given optimized surface tension coefficients for scaling the surface area term in the nonpolar contribution, these automated parameterization schemes with GBMV2 and GBSW demonstrate reasonable agreement with experimental hydration free energies (average unsigned errors of 0.9–1.5 kcal/mol and R² of 0.63–0.87). GBMV2 and GBSW consistently provide slightly more accurate estimates than FACTS, whereas Antechamber parameters yield marginally more accurate estimates than the current generation of MATCH, ParamChem, and SwissParam parameterization strategies. Modeling with MATCH libraries that are derived from different CHARMM topology and parameter files highlights the importance of having sufficient coverage of chemical space within the underlying databases of these automated schemes and the benefit of targeting specific functional groups for parameterization efforts to maximize both the breadth and the depth of the parameterized space. © 2013 Wiley Periodicals, Inc.     

Rapid approximate calculation of water binding free energies in the whole hydration domain of (bio)macromolecules

The evaluation of water binding free energies around solute molecules is important for the thermodynamic characterization of hydration or association processes. Here, a rapid approximate method to estimate water binding free energies around (bio)macromolecules from a single molecular dynamics simulation is presented. The basic idea is that endpoint free‐energy calculation methods are applied and the endpoint quantities are monitored on a three‐dimensional grid around the solute. Thus, a gridded map of water binding free energies around the solute is obtained, that is, from a single short simulation, a map of favorable and unfavorable water binding sites can be constructed. Among the employed free‐energy calculation methods, approaches involving endpoint information pertaining to actual thermodynamic integration calculations or endpoint information as exploited in the linear interaction energy method were examined. The accuracy of the approximate approaches was evaluated on the hydration of a cage‐like molecule representing either a nonpolar, polar, or charged water binding site and on α‐ and β‐cyclodextrin molecules. Among the tested approaches, the linear interaction energy method is considered the most viable approach. Applying the linear interaction energy method on the grid around the solute, a semi‐quantitative thermodynamic characterization of hydration around the whole solute is obtained. Disadvantages are the approximate nature of the method and a limited flexibility of the solute. © 2016 Wiley Periodicals, Inc.     

共价键稳定性的影响因素

虽然小分子中的共价键强度可以很方便地通过高斯计算而相当准确地得到,一些手册和数据库中也可以直接查出部分键能/离解能数据,但共价键的强弱变化的影响因素分析在化学教学中仍然显得非常重要。共价键的强弱与成键原子及其环境密切相关,其中成键原子因素主要包括原子半径、成键类型、成键轨道类型、相对论效应、电负性、成键数量、反馈效应和孤电子对效应,而成键环境因素包括键间张力效应、离域效应、次级化学键效应、诱导效应和位阻效应。在教学中,我们可以通过对化学键影响因素的分析帮助学生理解共价键键能的变化规律。本文分析了影响共价键强弱的主要因素,并介绍了这种分析思路在化学教学中的应用。     

MST continuum study of the hydration free energies of monovalent ionic species

In this study, we revisit the protocol previously proposed within the framework of the Miertus-Scrocco-Tomasi (MST) continuum model to define the cavity between the solute and solvent for predicting hydration free energies of univalent ions. The protocol relies on the use of a reduced cavity (around 10-15% smaller than the cavity used for neutral compounds) around the atom(s) bearing the formal charge. The suitability of this approach is examined here for a series of 47 univalent ions for which accurate experimental hydration free energies are available. Attention is also paid to the effect of the charge renormalization protocol used to correct uncertainties arising from the electron density located outside the solute cavity. The method presented here provides, with a minimum number of fitted parameters, reasonable estimates within the experimental error of the hydration free energy of ions (average relative error of 4.7%) and is able to reproduce solvation in water of both small and large ions.     

Why are the Homoleptic Diyl Complexes M(InR)4 with M = Ni and Pt Stable Compounds while only Ni(CO)4 but not Pt(CO)4 can become Isolated? A Theoretical Study of M(EMe)44 and M(CO)4 (M = Ni,Pd, Pt; E = B,Al, Ga,In, Tl)

The equilibrium geometries and first bond dissociation energies of the homoleptic complexes M(EMe)₄ and M(CO)₄ with M = Ni, Pd, Pt and E = B, Al, Ga, In, Tl have been calculated at the gradient corrected DFT level using the BP86 functionals. The electronic structure of the metal‐ligand bonds has been examined with the topologial analysis of the electron density distribution. The nature of the bonding is revealed by partitioning the metal‐ligand interaction energies into contributions by electrostatic attraction, covalent bonding and Pauli repulsion. The calculated data show that the M‐CO and M‐EMe bonding is very similar. However, the M‐EMe bonds of the lighter elements E are much stronger than the M‐CO bonds. The bond energies of the latter are as low or even lower than the M‐TlMe bonds. The main reason why Pd(CO)₄ and Pt(CO)₄ are unstable at room temperature in a condensed phase can be traced back to the already rather weak bond energy of the Ni‐CO bond. The Pd‐L bond energies of the complexes with L = CO and L = EMe are always 10 — 20 kcal/mol lower than the Ni‐L bond energies. The calculated bond energy of Ni(CO)₄ is only D_o = 27 kcal/mol. Thus, the bond energy of Pd(CO)₄ is only D_o = 12 kcal/mol. The first bond dissociation energy of Pt(CO)₄ is low because the relaxation energy of the Pt(CO)₃ fragment is rather high. The low bond energies of the M‐CO bonds are mainly caused by the relatively weak electrostatic attraction and by the comparatively large Pauli repulsion. The σ and π contributions to the covalent M‐CO interactions have about the same strength. The π bonding in the M‐EMe bonds is less than in the M‐CO bonds but it remains an important part of the bond energy. The trends of the electrostatic and covalent contributions to the bond energies and the σ and π bonding in the metal‐ligand bonds are discussed.     

Hydration of ionic species studied by the reference interaction site model with a repulsive bridge correction

We have tested the reference interaction site model (RISM) for the case of the hypernetted chain (HNC) and the partially linearized hypernetted chain (PLHNC) closures improved by a repulsive bridge correction (RBC) for ionic hydrated species. We have analyzed the efficiency of the RISM/HNC+RBC and RISM/PLHNC+RBC techniques for decomposition of the electrostatic and the nonpolar hydration energies on the energetic and the enthalpic parts for polyatomic ions when the repulsive bridge correction is treated as a thermodynamic perturbation, and investigate the repulsive bridge effect on the electrostatic potential induced by solvent on solute atoms. For a number of univalent and bivalent atomic ions, molecular cations, and anions, the method provides hydration energies deviating only by several percents from the experimental data. In most cases, the enthalpic contributions to the free energies are also close to the experimental results. The above models are able to satisfactory predict the hydration energies as well as the electrostatic potential around the ionic species. For univalent atomic ions, they also provide qualitative estimates of the Samoilov activation energies.     

Evaluating nonpolarizable nucleic acid force fields: A systematic comparison of the nucleobases hydration free energies and chloroform‐to‐water partition coefficients

Nucleic acid force fields have been shown to reproduce structural properties of DNA and RNA very well, but comparative studies with respect to thermodynamic properties are rare. As a test for thermodynamic properties, we have computed hydration free energies and chloroform‐to‐water partition coefficients of nucleobases using the AMBER‐99, AMBER‐gaff, CHARMM‐27, GROMOS‐45a4/53a6 and OPLS‐AA force fields. A mutual force field comparison showed a very large spread in the calculated thermodynamic properties, demonstrating that some of the parameter sets require further optimization. The choice of solvent model used in the simulation does not have a significant effect on the results. Comparing the hydration free energies obtained by the various force fields to the adenine and thymine experimental values showed a very large deviation for the GROMOS and AMBER parameter sets. Validation against experimental partition coefficients showed good agreement for the CHARMM‐27 parameter set. In view of mutation studies, differences in partition coefficient between two bases were also compared, and good agreement between experiments and calculations was found for the AMBER‐99 parameter set. Overall, the CHARMM‐27 parameter set performs best with respect to the thermodynamic properties tested here. © 2012 Wiley Periodicals, Inc.     

The investigation on the relative stability of different clusters of thiourea dioxide in water using gas phase quantum chemical calculations

The relative stability of different clusters of thiourea dioxide (TDO) in water is examined using gas phase quantum chemical calculations at the MP2 and B3LYP level with 6‐311++G(d,p) basis set. The possible equilibrium structures and other energetic and geometrical data of the thiourea dioxide clusters, TDO‐(H₂O)_n (n is the number of water molecules), are obtained. The calculation results show that a strong interaction exists between thiourea dioxide and water molecules, as indicated by the binding energies of the TDO clusters progressively increased by adding water molecules. PCM model is used to investigate solvent effect of TDO. We obtained a negative hydration energy of ?20.6 kcal mol^?1 and free‐energy change of ?21.0 kcal mol^?1 in hydration process. On the basis of increasing binding energies with adding water molecules and a negative hydration energy by PCM calculation, we conclude thiourea dioxide can dissolve in water molecules. Furthermore, the increases of the C? S bond distance by the addition of water molecules show that the strength of the C? S bonds is attenuated. We find that when the number of water molecules was up to 5, the C? S bonds of the clusters, TDO‐(H₂O)₅ and TDO‐(H₂O)₆ were ruptured. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009