First Principles Investigation of Noncovalent Complexation: A [2.2.2]‐Cryptand Ion‐Binding Selectivity Study

A first principles methodology, aimed at understanding the roles of molecular conformation and energetics in host–guest binding interactions, is developed and tested on a system that pushes the practical limits of ab initio methods. The binding behavior between the [2.2.2]‐cryptand host (4,7,13,16,21,24‐hexaoxa‐1,10‐diaza‐bicyclo[8.8.8]hexacosane) and alkali metal cations (Li⁺, Na⁺, and K⁺) in gas, water, methanol, and acetonitrile is characterized. Hartree–Fock and density functional theory methods are used in concert with crystallographic information to identify gas phase, energy‐minimized conformations. Gas phase free energies of binding, with vibrational contributions, are compared to solution‐state binding constants through relative binding selectivity analysis. Calculated relative binding free energies qualitatively correlated with solution state experiments only after gas phase metal desolvation is considered. The B3LYP exchange–correlation functional improves theoretical correlations with experimental relative binding free energies. The relevance of gas phase calculations towards understanding binding in condensed phases is discussed. Natural bond orbital methods highlights previously unidentified intramolecular and intermolecular M⁺(222) chemistries, such as an intramolecular n′_O→σ*_CH hydrogen bond.     

The effect of atomic and extra-atomic relaxation on atomic binding energies

An equivalent-cores-relaxation model is given for calculating atomic binding energies from orbital energies using only ground-state atomic properties. The agreement with experiment is excellent for the noble gases. On the basis of present knowledge of atomic relaxation, the phenomenon of “extra-atomic relaxation”, in which electronic charge is attracted toward a hole-state atom, is shown to have an important effect in lowering atomic core-level binding energies in condensed phases. This will affect the interpretation of most core-level binding energies measured to date.     

Accurate ab initio binding energies of the benzene dimer

Accurate binding energies of the benzene dimer at the T and parallel displaced (PD) configurations were determined using the single- and double-coupled cluster method with perturbative triple correction (CCSD(T)) with correlation-consistent basis sets and an effective basis set extrapolation scheme recently devised. The difference between the estimated CCSD(T) basis set limit electronic binding energies for the T and PD shapes appears to amount to more than 0.3 kcal/mol, indicating the PD shape is a more stable configuration than the T shape for this dimer in the gas phase. This conclusion is further strengthened when a vibrational zero-point correction to the electronic binding energies of this dimer is made, which increases the difference between the two configurations to 0.4-0.5 kcal/mol. The binding energies of 2.4 and 2.8 kcal/mol for the T and PD configurations are in good accord with the previous experimental result from ionization potential measurement.     

Resonance Energy Transfer Relates the Gas‐Phase Structure and Pharmacological Activity of Opioid Peptides

Enkephalins are efficient pain‐relief drugs that bind to transmembrane opioid receptors. One key structural parameter that governs the pharmacological activity of these opioid peptides and is typically determined from condensed‐phase structures is the distance between the aromatic rings of their Tyr and Phe residues. We use resonance energy transfer, detected by a combination of cold ion spectroscopy and mass spectrometry, to estimate the Tyr–Phe spacing for enkephalins in the gas phase. In contrast to the condensed‐phase structures, these distances appear to differ substantially in enkephalins with different pharmacological efficiencies, suggesting that gas‐phase structures might be a better pharmacophoric metric for ligand peptides.     

DFT and Ab initio computational study on the reactivity sites of the GABA and its agonists,such as CACA,TACA, DABA,and muscimol: In the gas phase and dielectric media

The reactive behavior of GABA and its agonist molecules have been investigated using B3LYP hybrid density functional method at the 6‐311++G** basis set level, in the gas phase and dielectric media. The calculations have been performed to obtain optimized geometries, relative energies, net atomic charges, HOMO, and LUMO energies. Solvent effects have been analyzed using isodensity polarized continuum model (IPCM) for four different solvents, which are chloroform, ethanol, DMSO, and H₂O. The results have suggested that both the amino group and carboxyl group have been two of the most important active site for interactions between all compounds and their receptors. In addition they have suggested that the amino group reflects the difference in biological activity for each all molecules. The structures of these agonists have provided an essential foundation for subsequent structure‐activity analysis of ligand binding at GABA receptors, neuronal uptake inhibitors and transporters. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

醛酮类化合物的分子力场参数推导及热力学性质计算

针对醛酮类分子, 基于第一原理的量子化学计算结果开发了准确、可迁移的全原子力场. 利用所得到的力场, 采用分子动力学和蒙特卡罗方法对醛酮类分子的气相分子结构、振动频率、构象能和凝聚相液体性质(密度和蒸发焓), 以及流体的多种热力学性质包括气液相平衡和临界性质, 与涨落相关的等压热容, 传递性质如剪切粘度等进行了计算和预测. 计算结果表明, 该力场可准确地反映气相分子的结构、振动频率、构象能和凝聚相液体密度和蒸发焓等性质, 并准确地预测一系列醛酮类分子的多种热力学性质. 所开发的醛酮类分子力场函数形式简单, 并具有良好的可迁移性和准确性, 在应用范围和计算精度上都有明显的改善和提高.     

Gaussian basis sets for accurate calculations on molecular systems in gas and condensed phases

We present a library of Gaussian basis sets that has been specifically optimized to perform accurate molecular calculations based on density functional theory. It targets a wide range of chemical environments, including the gas phase, interfaces, and the condensed phase. These generally contracted basis sets, which include diffuse primitives, are obtained minimizing a linear combination of the total energy and the condition number of the overlap matrix for a set of molecules with respect to the exponents and contraction coefficients of the full basis. Typically, for a given accuracy in the total energy, significantly fewer basis functions are needed in this scheme than in the usual split valence scheme, leading to a speedup for systems where the computational cost is dominated by diagonalization. More importantly, binding energies of hydrogen bonded complexes are of similar quality as the ones obtained with augmented basis sets, i.e., have a small (down to 0.2 kcal/mol) basis set superposition error, and the monomers have dipoles within 0.1 D of the basis set limit. However, contrary to typical augmented basis sets, there are no near linear dependencies in the basis, so that the overlap matrix is always well conditioned, also, in the condensed phase. The basis can therefore be used in first principles molecular dynamics simulations and is well suited for linear scaling calculations.     

Polarizable empirical force field for sulfur‐containing compounds based on the classical Drude oscillator model

Condensed‐phase computational studies of molecules using molecular mechanics approaches require the use of force fields to describe the energetics of the systems as a function of structure. The advantage of polarizable force fields over nonpolarizable (or additive) models lies in their ability to vary their electronic distribution as a function of the environment. Toward development of a polarizable force field for biological molecules, parameters for a series of sulfur‐containing molecules are presented. Parameter optimization was performed to reproduce quantum mechanical and experimental data for gas phase properties including geometries, conformational energies, vibrational spectra, and dipole moments as well as for condensed phase properties such as heats of vaporization, molecular volumes, and free energies of hydration. Compounds in the training set include methanethiol, ethanethiol, propanethiol, ethyl methyl sulfide, and dimethyl disulfide. The molecular volumes and heats of vaporization are in good accordance with experimental values, with the polarizable model performing better than the CHARMM22 nonpolarizable force field. Improvements with the polarizable model were also obtained for molecular dipole moments and in the treatment of intermolecular interactions as a function of orientation, in part due to the presence of lone pairs and anisotropic atomic polarizability on the sulfur atoms. Significant advantage of the polarizable model was reflected in calculation of the dielectric constants, a property that CHARMM22 systematically underestimates. The ability of this polarizable model to accurately describe a range of gas and condensed phase properties paves the way for more accurate simulation studies of sulfur‐containing molecules including cysteine and methionine residues in proteins. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Calculation of relaxed orbital binding energies in atoms: Zinc and cadmium

Relaxed orbital binding energies of electrons in zinc and cadmium are calculated using a relativistic local density functional theory. The discrepancy between our calculated binding energies and those from gas phase experimental data are attributed to inhomogeniety and many body effects.     

Uranyl complexes with diamide ligands: a quantum mechanics study of chelating properties in the gas phase

We report a quantum mechanical study on the complexes of UO(2)(2+) with diamide ligands L of malonamide and succinamide type, respectively, forming 6- and 7-chelate rings in their bidentate coordination to uranium. The main aims are to (i) assess how strong the chelate effect is (i.e., the preference for bi- versus monodentate binding modes of L), (ii) compare these ligands as a function of the chelate ring size, and (iii) assess the role of neutralizing counterions. For this purpose, we consider UO(2)L(2+), UO(2)L(2)(2+), UO(2)L(3)(2+), and UO(2)X(2)L type complexes with X(-) = Cl(-) versus NO(3)(-). Hartree-Fock and DFT calculations lead to similar trends and reveal the importance of saturation and steric repulsions ("strain") in the first coordination sphere. In the unsaturated UO(2)L(2+), UO(2)L(2)(2+), and UO(2)Cl(2)L complexes, the 7-ring chelate is preferred over the 6-ring chelate, and bidentate coordination is preferred over the monodentate one. However, in the saturated UO(2)(NO(3))(2)L complexes, the 6- and 7-chelating ligands have similar binding energies, and for a given ligand, the mono- and bidentate binding modes are quasi-isoenergetic. These conclusions are confirmed by the calculations of free energies of complexation in the gas phase. In condensed phases, the monodentate form of UO(2)X(2)L complexes should be further stabilized by coordination of additional ligands, as well as by interactions (e.g., hydrogen bonding) of the "free" carbonyl oxygen, leading to an enthalpic preference for this form, compared to the bidentate one. We also considered an isodesmic reaction exchanging one bidentate ligand L with two monoamide analogues, which reveals that the latter are clearly preferred (by 23-14 kcal/mol at the HF level and 24-12 kcal/mol at the DFT level). Thus, in the gas phase, the studied bidentate ligands are enthalpically disfavored, compared to bis-monodentate analogues. The contrast with trends observed in solution hints at the importance of "long range" forces (e.g., second shell interactions) and entropy effects on the chelate effect in condensed phases.     

Density functional theory study of 1:1 glycine-water complexes in the gas phase and in solution

We present a systematic study of 1:1 glycine-water complexes involving all possible glycine conformers. The complex geometries are fully optimized for the first time both in the gas phase and in solution using three DFT methods (B3LYP, PBE1PBE, X3LYP) and the MP2 method. We calculate the G3 energies and use them as the reference data to gauge hydrogen bond strength in the gas phase. The solvent effects are treated via the integral equation formalism-polarizable continuum model (IEF-PCM). Altogether, we locate fifty-two unique nonionized (N) structures and six zwitterionic (Z) structures in the gas phase, and fifty-five N structures and thirteen Z structures in solution. Both correlation and solvation are shown to be important in geometry determination. We found that in the gas phase, a water molecule binds more strongly to the carboxylic acid group of glycine than to its amine group, whereas in solution phase the reverse is true. The most stable Z structure is isoenergetic with the most stable N structure.     

Ab Initio Study of the Stepwise versus Concerted Fragmentation Pathways in Microhydrated Thymine Radical Cations

Thymine radiation-induced fragmentation is characterised by ring opening and the loss of HNCO/NCO. These pathways have been investigated using DFT calculations in the presence of zero, one and two water molecules. In addition to the already characterised stepwise fragmentation mechanism, we propose a novel concerted pathway reported here for the first time. We show that both the stepwise and concerted mechanisms are competitive with activation energies of 2.05 eV and 2.00 eV, respectively, in the gas phase. The effect of microhydration on these mechanisms are examined based on the most stable conformations found by an exploration of the potential energy surface performed by using DFT-based ab initio molecular dynamics. Microhydration is also accompanied by an increase in the activation energies, with respect to gas phase, amounting to 0.47 eV—an increase that is associated to a stabilising effect of water in agreement with recent experimental studies. However, we also point out that this effect is greatly dependent on the specific water arrangement around thymine and could be limited to only 0.13 eV for some configurations.     

Theoretical investigation on the performance of simple and doped graphenes for the surface adsorption of various ions and water desalination

In this work, the abilities of simple and heteroatom-doped graphenes for the adsorption of several ions (sodium, calcium, magnesium, chloride, carbonate, sulfate, and nitrate) were studied using theoretical methods. The results of this work could be helpful for future studies in the water desalination projects because the considered ions are the major existing ions in water. The structures of all graphenes and their complexes with these ions were optimized in the gas phase and water (using PCM model). Moreover, the interaction energies in the gas phase and water, atomic charges, second-order perturbation energies (from NBO calculations), and QTAIM results were obtained to provide more evidences related to these interactions. The obtained energies showed more favorable interactions in water versus than those in the gas phase. Among all graphenes, aluminum-doped graphene showed the highest and nitrogen-doped graphene showed the least adsorption energies. QTAIM calculations indicated the noticeable electron densities in bond critical points for all interactions, and the Laplacians of electron densities confirmed nonbonding nature for the most of interactions. Population analyses revealed that the HOMO-LUMO gap in doped graphene was increased in comparing with simple graphene that make them as potential candidates for detection of these ions.     

New stable multiply charged negative atomic ions in linearly polarized superintense laser fields

Singly charged negative atomic ions exist in the gas phase and are of fundamental importance in atomic and molecular physics. However, theoretical calculations and experimental results clearly exclude the existence of any stable doubly-negatively-charged atomic ion in the gas phase, only one electron can be added to a free atom in the gas phase. In this report, using the high-frequency Floquet theory, we predict that in a linear superintense laser field one can stabilize multiply charged negative atomic ions in the gas phase. We present self-consistent field calculations for the linear superintense laser fields needed to bind extra one and two electrons to form He-, He2-, and Li2-, with detachment energies dependent on the laser intensity and maximal values of 1.2, 0.12, and 0.13 eV, respectively. The fields and frequencies needed for binding extra electrons are within experimental reach. This method of stabilization is general and can be used to predict stability of larger multiply charged negative atomic ions.     

Uncatalyzed transfer hydrogenation of quinones and related systems: a theoretical mechanistic study

Quantum chemistry calculations have been used to study the uncatalyzed transfer hydrogenation between a range of hydrogen donors and acceptors, in the gas phase and in solution. Our study shows in the first place that in order to obtain reliable condensed-phase transition structures, it is necessary to perform geometry optimization in the presence of a continuum. In addition, the use of a free energy of solvation obtained with the UB3-LYP/6-31+G(d,p)/IEF-PCM/UA0 combination, in conjunction with UMPWB1K/6-311+G(3df,2p)//B3-LYP/6-31+G(d,p) gas-phase energies, gives the best agreement with experimental barriers. In condensed phases, the geometries and energies of the transition structures are found to relate to one another in a manner consistent with the Hammond postulate. There is also a correlation between the barriers and the energies of the radical intermediates in accord with the Bell-Evans-Polanyi principle. We find that in the gas phase, all the transfer-hydrogenation reactions examined proceed via a radical pathway. In condensed phases, some of the reactions follow a radical mechanism regardless of the solvent. However, for some reactions there is a change from a radical mechanism to an ionic mechanism as the solvent becomes more polar. Our calculations indicate that the detection of radical adducts by EPR does not necessarily indicate a predominant radical mechanism, because of the possibility of a concurrent ionic reaction. We also find that the transition structures for these reactions do not necessarily have a strong resemblance to the intermediates, and therefore one should be cautious in utilizing the influence of polar effects on the rate of reaction as a means of determining the mechanism.     

Ab initio study of hydrogen-bond formation between aliphatic and phenolic hydroxy groups and selected amino acid side chains

Hydrogen bonding was studied in 24 pairs of isopropyl alcohol and phenol as one partner, and water and amino-acid mimics (methanol, acetamide, neutral and protonated imidazole, protonated methylalamine, methyl-guanidium cation, and acetate anion) as the other partner. MP2/6-31+G* and MP2/aug-cc-pvtz calculations were conducted in the gas phase and in a model continuum dielectric environment with dielectric constant of 15.0. Structures were optimized in the gas phase with both basis sets, and zero-point energies were calculated at the MP2/6-31+G* level. At the MP2/aug-cc-pvtz level, the BSSE values from the Boys-Bernardi counterpoise calculations amount to 10-20 and 5-10% of the uncorrected binding energies of the neutral and ionic complexes, respectively. The geometry distortion energy upon hydrogen-bond formation is up to 2 kcal/mol, with the exception of the most strongly bound complexes. The BSSE-corrected MP2/aug-cc-pvtz binding energy of -27.56 kcal/mol for the gas-phase acetate...phenol system has been classified as a short and strong hydrogen bond (SSHB). The CH3NH3+...isopropyl alcohol complex with binding energy of -22.54 kcal/mol approaches this classification. The complete basis set limit (CBS) for the binding energy was calculated for twelve and six complexes on the basis of standard and counterpoise-corrected geometry optimizations, respectively. The X...Y distances of the X-H...Y bridges differ by up to 0.03 A as calculated by the two methods, whereas the corresponding CBS energy values differ by up to 0.03 kcal/mol. Uncorrected MP2/aug-cc-pvtz hydrogen-bonding energies are more negative by up to 0.35 kcal/mol than the MP2/CBS values, and overestimate the CCSD(T)/CBS binding energies generally by up to 5% for the eight studied complexes in the gas phase. The uncorrected MP2/aug-cc-pvtz binding energies decreased (in absolute value) by 11-18 kcal/mol for the ionic species and by up to 5 kcal/mol for the neutral complexes when the electrostatic effect of a polarizable model environment was considered. The DeltaECCSD(T) - DeltaEMP2 corrections still remained close to their gas-phase values for four complexes with 0, +/-1 net charges. Good correlations (R2 = 0.918-0.958) for the in-environment MP2/aug-cc-pvtz and MP2/6-31+G* hydrogen-bonding energies facilitate the high-level prediction of these energies on the basis of relatively simple MP2/6-31+G* calculations.     

金属离子与腺嘌呤异构体复合物的稳定性

在B3LYP/6-311++G**//6-31+G*基组水平上结合PCM模型系统的优化了气相和液相环境中14种腺嘌呤异构体与四种金属离子(Na+,K+,Mg2+,Ca2+)形成的132个稳定复合物。通过能量对比,得到了所有复合物异构体在气液两相中的稳定性顺序及不同金属离子与同一异构体形成的复合物的能量排序,首次给出了液相中这些不同金属离子复合物的最稳定结构。结果发现溶剂效应导致了液相中的复合物稳定性顺序与气相中的相比发生了很大变化;同一异构体与不同金属离子形成的复合物其稳定性在排序中也变化很大。对于这些变化,本文分别从金属离子与腺嘌呤的复合物在气相中的结合能(EBE)及在液相中的溶质溶剂相互作用能(Epol)能等方面进行了系统的阐述     

Observations of tetrel bonding between sp3-carbon and THF

We report the direct observation of tetrel bonding interactions between sp³-carbons of the supramolecular synthon 3,3-dimethyl-tetracyanocyclopropane (1) and tetrahydrofuran in the gas and crystalline phase. The intermolecular contact is established via σ-holes and is driven mainly by electrostatic forces. The complex manifests distinct binding geometries when captured in the crystalline phase and in the gas phase. We elucidate these binding trends using complementary gas phase quantum chemical calculations and find a total binding energy of −11.2 kcal mol⁻¹ for the adduct. Our observations pave the way for novel strategies to engineer sp³-C centred non-covalent bonding schemes for supramolecular chemistry.

sp³-C⋯THF tetrel bonding was observed in the crystalline state and in the gas phase. Density functional calculations revealed interaction energies up to −11.2 kcal mol⁻¹ and showed that these adducts are held together mainly by electrostatics.     

CHARMM fluctuating charge force field for proteins: I parameterization and application to bulk organic liquid simulations

A first-generation fluctuating charge (FQ) force field to be ultimately applied for protein simulations is presented. The electrostatic model parameters, the atomic hardnesses, and electronegativities, are parameterized by fitting to DFT-based charge responses of small molecules perturbed by a dipolar probe mimicking a water dipole. The nonbonded parameters for atoms based on the CHARMM atom-typing scheme are determined via simultaneously optimizing vacuum water-solute geometries and energies (for a set of small organic molecules) and condensed phase properties (densities and vaporization enthalpies) for pure bulk liquids. Vacuum solute-water geometries, specifically hydrogen bond distances, are fit to 0.19 A r.m.s. error, while dimerization energies are fit to 0.98 kcal/mol r.m.s. error. Properties of the liquids studied include bulk liquid structure and polarization. The FQ model does indeed show a condensed phase effect in the shifting of molecular dipole moments to higher values relative to the gas phase. The FQ liquids also appear to be more strongly associated, in the case of hydrogen bonding liquids, due to the enhanced dipolar interactions as evidenced by shifts toward lower energies in pair energy distributions. We present results from a short simulation of NMA in bulk TIP4P-FQ water as a step towards simulating solvated peptide/protein systems. As expected, there is a nontrivial dipole moment enhancement of the NMA (although the quantitative accuracy is difficult to assess). Furthermore, the distribution of dipole moments of water molecules in the vicinity of the solutes is shifted towards larger values by 0.1-0.2 Debye in keeping with previously reported work.