The non-covalent functionalisation of carbon nanotubes studied by density functional and semi-empirical molecular orbital methods including dispersion corrections

Density functional theory (DFT-D) and semi-empirical (PM3-D) methods having an added empirical dispersion correction have been used to study the binding of a series of small molecules and planar aromatic molecules to single-walled carbon nanotubes (CNTs). For the small molecule set, the PM3-D method gives a mean unsigned error (MUE) in the binding energies of 1.2 kcal mol(-1) when judged against experimental reference data for graphitic carbon. This value is close to the MUE for this method compared to high-level ab initio data for biological complexes. The PM3-D and DFT-D calculations describing the adsorption of the planar organic molecules (benzene, bibenzene, naphthalene, anthracene, TCNQ and DDQ) on the outer-walls of both semi-conducting and metallic CNTs give similar binding energies for benzene and DDQ, but do not display a stronger adsorption on [6,6] compared to [10,0] structures shown by another DFT study.     

Adsorption of spillover hydrogen atoms on single-wall carbon nanotubes

Spillover of hydrogen on nanostructured carbons is a phenomenon that is critical to understand in order to produce efficient hydrogen storage adsorbents for fuel cell applications. The spillover and interaction of atomic hydrogen with single-walled carbon nanotubes (SWNTs) is the focus of this combined theoretical and experimental work. To understand the spillover mechanism, very low occupancies (i.e., 1 and 2 H atoms adsorbed) on (5,0), (7,0), (9,0) zigzag (semiconducting) SWNTs and a (5,5) armchair (metallic) SWNT, with corresponding diameters of 3.9, 5.5, 7.0, and 6.8 A, were investigated. The adsorption binding energy of H atoms depends on H occupancy, tube diameter, and helicity (or chirality), as well as endohedral (interior) vs exohedral (exterior) binding. Exohedral binding energies are substantially higher than endohedral binding energies due to easier sp(2)-sp(3) transition in hybridization of carbon on exterior walls upon binding. A binding energy as low as -8.9 kcal/mol is obtained for 2H atoms on the exterior wall of a (5, 0) SWNT. The binding energies of H atoms on the metallic SWNT are significantly weaker (about 23 kcal/mol weaker) than that on the semiconductor SWNT, for both endohedral and exohedral adsorption. The binding energy is generally higher on SWNTs of larger diameters, while its dependence on H occupancy is relatively weak except at very low occupancies. Experimental results at 298 K and for pressures up to 10 MPa with a carbon-bridged composite material containing SWNTs demonstrate the presence of multiple adsorption sites based on desorption hysteresis for the spiltover H on SWNTs, and the experimental results were in qualitative agreement with the molecular orbital calculation results.     

Interactions of hydrogen with Pd and Pd/Ni alloy chain-functionalized single walled carbon nanotubes from density functional theory

Density functional theory is employed to study Pd and Pd/Ni alloy monatomic chain-functionalized metallic single walled carbon nanotubes (SWNT(6,6)) and semiconducting SWNT(10,0), and their interactions with hydrogen molecules. The stable geometries and binding energies have been determined for both isolated chains and chains on SWNT surfaces. We found that continuous Pd and Pd/Ni chains form on SWNTs with geometries close to stable geometries in the isolated chains. Ni alloying improves stability of the chains owing to a higher binding energy to both Pd and C atoms. The physical properties of SWNTs are significantly modified by chain functionalization. SWNT(10,0) is transformed to metal by either Pd or alloy chains, or to a smaller band gap semiconductor, depending on the Pd binding site. From calculations for H(2) interactions with the optimized chain-SWNT systems, the adsorption energy per H atom is found to be about 2.6 times larger for Pd/Ni chain-functionalized SWNTs than for pure Pd chain-functionalized SWNTs. Band structure calculations show that the SWNT(10,0) reverts back to semiconductor and SWNT(6,6) has reduced density of states at the Fermi level upon H(2) adsorption. This result is consistent with the experimentally observed increase of electrical resistance when Pd-coated SWNTs are used as H(2) sensing materials. Finally, our results suggest that Pd/Ni-SWNT materials are potentially good H(2)-sensing materials.     

Theoretical characterization of thioepoxidated single wall carbon nanotubes

We have studied the external addition of sulfur to the walls of the (5,5) and (10,0) SWCNTs forming a cyclic thioepoxide. The binding energies are close to 32 kcal/mol, but they can be increased to 41 kcal/mol if the sulfur atoms are added forming a line along the axis of the (10,0) SWCNT. The addition of sulfur atoms to the (5,5) SWCNT alters the DOS but the tubes remains metallic. However, for the (10,0) SWCNT the exothermic addition of sulfur atoms can induce strong changes in the DOS, depending on the amount of sulfur atoms added. When we included one sulfur per 120 carbons, the (10,0) SWCNT showed metallic properties.     

A dispersion-corrected density functional theory study of the noncovalent interactions between nucleobases and carbon nanotube models containing stone–wales defects

The noncovalent bonding between nucleobases (NBs) and Stone–Wales (SW) defect-containing closed-end single-walled carbon nanotubes (SWNTs) was theoretically studied in the framework of density function theory using a dispersion-corrected functional PBE-G06/DNP. The models employed in this study were armchair nanotube (ANT) (5,5) and zigzag nanotube (ZNT) (10,0), which incorporated SW defects in different orientations. In one of them, the (7,7) junction is tilted with respect to SWNT axis (ANT-t and ZNT-t), whereas in ANT-p and ZNT-p models the (7,7) junction is parallel and perpendicular to the axis, respectively. The binding energies for uracil, thymine, cytosine, 5-methylcytosine, adenine, and guanine interacting with the defect-containing nanotube models were compared to the values previously obtained with the same calculation technique for the case of defect-free SWNTs, both in the gas phase (vacuum) and in aqueous medium. For most models, the interaction strength tends to be higher for purine than for pyrimidine complexes, with a clear exception of the systems including ZNT-p, both in vacuum and in aqueous medium. As it could be expected, the binding strength in the latter case is lower as compared to that in vacuum, roughly by 2–4 kcal/mol, due to the implicit inclusion of a medium (i.e., water) via the conductor-like screening model model. The closest contacts between NBs and SWNT models, frontier orbital distribution, and highest-occupied molecular orbital–lowest-unoccupied molecular orbital gap energies are analyzed as well. © 2019 Wiley Periodicals, Inc.     

Comprehensive thermochemistry of W-H bonding in the metal hydrides CpW(CO)2(IMes)H, [CpW(CO)2(IMes)H](•+), and [CpW(CO)2(IMes)(H)2]+. Influence of an N-heterocyclic carbene ligand on metal hydride bond energies

The free energies interconnecting nine tungsten complexes have been determined from chemical equilibria and electrochemical data in MeCN solution (T = 22 °C). Homolytic W-H bond dissociation free energies are 59.3(3) kcal mol(-1) for CpW(CO)(2)(IMes)H and 59(1) kcal mol(-1) for the dihydride [CpW(CO)(2)(IMes)(H)(2)](+) (where IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene), indicating that the bonds are the same within experimental uncertainty for the neutral hydride and the cationic dihydride. For the radical cation, [CpW(CO)(2)(IMes)H](?+), W-H bond homolysis to generate the 16-electron cation [CpW(CO)(2)(IMes)](+) is followed by MeCN uptake, with free energies for these steps being 51(1) and -16.9(5) kcal mol(-1), respectively. Based on these two steps, the free energy change for the net conversion of [CpW(CO)(2)(IMes)H](?+) to [CpW(CO)(2)(IMes)(MeCN)](+) in MeCN is 34(1) kcal mol(-1), indicating a much lower bond strength for the 17-electron radical cation of the metal hydride compared to the 18-electron hydride or dihydride. The pK(a) of CpW(CO)(2)(IMes)H in MeCN was determined to be 31.9(1), significantly higher than the 26.6 reported for the related phosphine complex, CpW(CO)(2)(PMe(3))H. This difference is attributed to the electron donor strength of IMes greatly exceeding that of PMe(3). The pK(a) values for [CpW(CO)(2)(IMes)H](?+) and [CpW(CO)(2)(IMes)(H)(2)](+) were determined to be 6.3(5) and 6.3(8), much closer to the pK(a) values reported for the PMe(3) analogues. The free energy of hydride abstraction from CpW(CO)(2)(IMes)H is 74(1) kcal mol(-1), and the resultant [CpW(CO)(2)(IMes)](+) cation is significantly stabilized by binding MeCN to form [CpW(CO)(2)(IMes)(MeCN)](+), giving an effective hydride donor ability of 57(1) kcal mol(-1) in MeCN. Electrochemical oxidation of [CpW(CO)(2)(IMes)](-) is fully reversible at all observed scan rates in cyclic voltammetry experiments (E° = -1.65 V vs Cp(2)Fe(+/0) in MeCN), whereas CpW(CO)(2)(IMes)H is reversibly oxidized (E° = -0.13(3) V) only at high scan rates (800 V s(-1)). For [CpW(CO)(2)(IMes)(MeCN)](+), high-pressure NMR experiments provide an estimate of ΔG° = 10.3(4) kcal mol(-1) for the displacement of MeCN by H(2) to give [CpW(CO)(2)(IMes)(H)(2)](+).     

Electronic structures and energetics of [5,5] and [9,0] single-walled carbon nanotubes

Standard enthalpies of formation, ionization potentials, electron affinities, and band gaps of finite-length [5,5] armchair and [9,0] zigzag single-walled carbon nanotubes (SWNTs) capped with C(30) hemispheres obtained by halving the C(60) fullerene have been computed at the B3LYP/6-311G* level of theory. Properties of SWNTs are found to depend strongly on the tube length and, in the case of the [9,0] zigzag species, on the relative orientation of the caps. The metallic character of an uncapped infinite-length [5,5] armchair SWNT manifests itself in the oscillatory dependence of the properties of capped finite-length tubes on their size. An infinite-length [9,0] zigzag SWNT is predicted to be a semiconductor rather than a metal irrespective of the presence of caps. The present results underscore the slow convergence of SWNT properties with respect to the tube length and uncover small but significant radial distortions along the long axes of SWNTs.     

Ni adsorption on Stone-Wales defect sites in single-wall carbon nanotubes

Ni adsorption on Stone-Wales defect sites in (10,0) zigzag and (5,5) armchair single-wall carbon nanotubes was studied using the density functional theory. The stable adsorption sites and their binding energies on different Stone-Wales defect types were analyzed and compared to those on perfect side walls. It was determined that the sites formed via fusions of 7-7 and 6-7 rings are the most exothermic in the cases of (10,0) and (5,5) defective tubes. In addition C-C bonds associated with Stone-Wales defects are more reactive than the case for a perfect hexagon, thus enhancing the stability of the Ni adsorption. Moreover, the Ni adsorption was found to show a noticeable relationship to the orientation of the Stone-Wales defects with respect to the tube axis. The nature of the Ni adsorption on Stone-Wales defects that have the similar orientation is identical, in spite of the different chiralities.     

Heats of formation of [2.2]paracyclophane-1-ene and [2.2]paracyclophane-1,9-diene - an experimental study

The enthalpies of formation [Delta(g)] of tricyclo[8.2.2.2(4,7)]hexadeca-1(13),2,4(16),5,7(15),10(14),11-heptaene (2, 1,2-dehydro[2.2]paracyclophane or [2.2]paracyclophane-1-ene) and tricyclo[8.2.2.2(4,7)]hexadeca-1(13),2,4(16),5,7(15),8,10(14),11-octaene (3, 1,2,9,10-dehydro[2.2]paracyclophane or [2.2]paracyclophane-1,9-diene) have been determined by measuring their heats of combustion in a microcalorimeter and their heats of sublimation by the transpiration method. Values of the strain energies (SE) [SE(2) = 34.7 kcal mol(-)(1), SE(3) = 42.0 kcal mol(-)(1)] have been derived from the gas-phase heats of formation and are compared with those from MM3 and PM3 calculations and with the corresponding value SE(1) = 30.1 kcal mol(-)(1) for the parent tricyclo[8.2.2.2(4,7)]hexadeca-1(13),4(16),5,7(15),10(14),11-hexaene (1, [2.2]paracyclophane). The higher strain energies of 2 and 3 (by 4.6 and 11.9 kcal mol(-)(1)) are in accord with the well-known increased reactivities of their aromatic rings as a consequence of their increased bending. As revealed by an X-ray crystal structure analysis, the bending in the monoene 2 corresponds to that of 1 and 3 at one of two bridging corners.     

Theoretical Evidence for the Stronger Ability of Thymine to Disperse SWCNT than Cytosine and Adenine: self-stacking of DNA bases vs their cross-stacking with SWCNT

Self-stacking of four DNA bases, adenine (A), cytosine (C), guanine (G) and thymine (T), and their cross-stacking with (5,5) as well as (10,0) single walled carbon nanotubes (SWCNTs) were extensively investigated with a novel hybrid DFT method, MPWB1K/cc-pVDZ. The binding energies were further corrected with MP2/6-311++G(d,p) method in both gas phase and aqueous solution, where the solvent effects were included with conductor-like polarized continuum model (CPCM) model and UAHF radii. The strongest self-stacking of G and A takes displaced anti-parallel configuration, but un-displaced or "eclipsed" anti-parallel configuration is the most stable for C and T. In gas phase the self-stacking of nucleobases decreases in the sequence G>A>C>T, while because of quite different solvent effects their self-stacking in aqueous solution exhibits a distinct sequence A>G>T>C. For a given base, cross-stacking is stronger than self-stacking in both gas phase and aqueous solution. Binding energy for cross-stacking in gas phase varies as G>A>T>C for both (10,0) and (5,5) SWCNTs, and the binding of four nucleobases to (10,0) is slightly stronger than to (5,5) SWCNT by a range of 0.1-0.5 kcal/mol. The cross-stacking in aqueous solution varies differently from that gas phase: A>G>T>C for (10,0) SWCNT and G>A>T>C for (5,5) SWCNT. It is suggested that the ability of nucleobases to disperse SWCNT depends on relative strength [Formula: see text] of self-stacking and cross-stacking with SWCNT in aqueous solution. Of the four investigated nucleobases thymine (T) exhibits the highest [Formula: see text] which can well explain the experimental finding that T more efficiently functionalizes SWCNT than C and A.     

Conformational features and anion-binding properties of calix[4]pyrrole: a theoretical study

The conformational preference of calix[4]pyrrole and its fluoride and chloride anion-binding properties have been investigated by density functional theory calculations. Geometries were optimized by the BLYP/3-21G and BLYP/6-31G methods, and energies were evaluated with the BLYP/6-31+G method. To model the effect of medium, the SCIPCM solvent model was also employed. Four typical conformations of the parent substituent-free calix[4]pyrrole were studied. Both in the gas phase and in CH(2)Cl(2) solution, the stability sequence is predicted to be 1,3-alternate > partial cone > 1,2-alternate > cone. The cone conformation is predicted to be about 16.0 and 11.4 kcal/mol less stable in the gas phase and CH(2)Cl(2) solution, respectively. This is mainly due to electrostatic repulsions arising from the all-syn pyrrole/pyrrole/pyrrole/pyrrole arrangement present in this conformer. The existence of possible 1:1 and 1:2 anion-binding modes were explored in the case of fluoride anion, and the factors favoring the 1:1 binding mode are discussed. The calculated binding energy for fluoride anion is about 15 kcal/mol larger than that for chloride anion. The calculated binding energy for chloride anion agrees with the experimental value very well. The presence of meso-alkyl substituents destabilizes the cone conformer with respect to the 1,3-alternate conformer and, therefore, reduces the anion-binding affinity by 3-4 kcal/mol. The strength of N-H- - -anion hydrogen bonds in the various structures subject to study were estimated on the basis of the calculated anion-binding energies and the predicted structural deformation energies of substituent-free calix[4]pyrrole.     

Interaction of atomic hydrogen with single-walled carbon nanotubes: a density functional theory study

We have studied the interaction of atomic hydrogen with (5,5) and (10,0) single-walled carbon nanotubes (SWNT) using density functional theory. These calculations use Gaussian orbitals and periodic boundary conditions. We compare results from the local spin density approximation, generalized gradient approximation (GGA), and hybrid density functionals. We have first kept the SWNT geometric structure fixed while a single H atom approaches the tube on top of a carbon atom. In that case, a weakly bound state with binding energies from -0.8 to -0.4 eV was found. Full geometry relaxation leads to a strong SWNT deformation, weakening the nearest C-C bonds and increasing the binding energy by about 1 eV. Full hydrogen coverage of the (5,5) SWNT converts this metallic nanotube into an insulator with a band gap of 3.4 eV for the GGA functional and 4.8 eV for the hybrid functional. Hybrid functionals perform similar to pure density functional theory functionals for the calculation of binding energies while band gaps critically depend on the functional choice.     

Thermodynamic and kinetic studies of H atom transfer from HMo(CO)3(eta(5)-C5H5) to Mo(N[t-Bu]Ar)3 and (PhCN)Mo(N[t-Bu]Ar)3: direct insertion of benzonitrile into the Mo-H bond of HMo(N[t-Bu]Ar)3 forming (Ph(H)C=N)Mo(N[t-Bu]Ar)3

Synthetic studies are reported that show that the reaction of either H2SnR2 (R = Ph, n-Bu) or HMo(CO)3(Cp) (1-H, Cp = eta(5)-C5H5) with Mo(N[t-Bu]Ar)3 (2, Ar = 3,5-C6H3Me2) produce HMo(N[t-Bu]Ar)3 (2-H). The benzonitrile adduct (PhCN)Mo(N[t-Bu]Ar)3 (2-NCPh) reacts rapidly with H2SnR2 or 1-H to produce the ketimide complex (Ph(H)C=N)Mo(N[t-Bu]Ar)3 (2-NC(H)Ph). The X-ray crystal structures of both 2-H and 2-NC(H)Ph are reported. The enthalpy of reaction of 1-H and 2 in toluene solution has been measured by solution calorimetry (DeltaH = -13.1 +/- 0.7 kcal mol(-1)) and used to estimate the Mo-H bond dissociation enthalpy (BDE) in 2-H as 62 kcal mol(-1). The enthalpy of reaction of 1-H and 2-NCPh in toluene solution was determined calorimetrically as DeltaH = -35.1 +/- 2.1 kcal mol(-1). This value combined with the enthalpy of hydrogenation of [Mo(CO)3(Cp)]2 (1(2)) gives an estimated value of 90 kcal mol(-1) for the BDE of the ketimide C-H of 2-NC(H)Ph. These data led to the prediction that formation of 2-NC(H)Ph via nitrile insertion into 2-H would be exothermic by approximately 36 kcal mol(-1), and this reaction was observed experimentally. Stopped flow kinetic studies of the rapid reaction of 1-H with 2-NCPh yielded DeltaH(double dagger) = 11.9 +/- 0.4 kcal mol(-1), DeltaS(double dagger) = -2.7 +/- 1.2 cal K(-1) mol(-1). Corresponding studies with DMo(CO)3(Cp) (1-D) showed a normal kinetic isotope effect with kH/kD approximately 1.6, DeltaH(double dagger) = 13.1 +/- 0.4 kcal mol(-1) and DeltaS(double dagger) = 1.1 +/- 1.6 cal K(-1) mol(-1). Spectroscopic studies of the much slower reaction of 1-H and 2 yielding 2-H and 1/2 1(2) showed generation of variable amounts of a complex proposed to be (Ar[t-Bu]N)3Mo-Mo(CO)3(Cp) (1-2). Complex 1-2 can also be formed in small equilibrium amounts by direct reaction of excess 2 and 1(2). The presence of 1-2 complicates the kinetic picture; however, in the presence of excess 2, the second-order rate constant for H atom transfer from 1-H has been measured: 0.09 +/- 0.01 M(-1) s(-1) at 1.3 degrees C and 0.26 +/- 0.04 M(-1) s(-1) at 17 degrees C. Study of the rate of reaction of 1-D yielded kH/kD = 1.00 +/- 0.05 consistent with an early transition state in which formation of the adduct (Ar[t-Bu]N)3Mo...HMo(CO)3(Cp) is rate limiting.     

Selective anion encapsulation by a metalated cryptophane with a pi-acidic interior

Metalation of the exterior arene faces of the molecular capsule (+/-)-cryptophane-E with [Cp*Ru]+ moieties results in a pi-acidic cavity capable of encapsulating anions. The [CF3SO3]- and [SbF6]- salts have been crystallographically characterized and demonstrate the encapsulation of these anions by the metalated cryptophane. 1H and 19F NMR spectroscopy establish the binding of anions in NO2CD3 solution and reveal the relative affinity of the cavity for different anions (KX-/KOTf-): [BF4]- approximately 0, [PF6]- = 1.18, [CF3SO3]- identical with 1, [SbF6]- = 0.30. Variable temperature rate studies reveal the activation barrier for triflate encapsulation to be DeltaG298K = 18.0(8) kcal.mol-1 (DeltaH = 17.5(4) kcal.mol-1 and DeltaS = 2(1) cal.mol-1.K-1).     

Mechanism of olefin metathesis with catalysis by ruthenium carbene complexes: density functional studies on model systems

Gradient-corrected (BP86) density functional calculations were used to study alternative mechanisms of the metathesis reactions between ethene and model catalysts [(PH(3))(L)Cl(2)Ru[double bond]CH(2)] with L=PH3 (I) and L=C(3)N(2)H(4)=imidazol-2-ylidene (II). On the associative pathway, the initial addition of ethene is calculated to be rate-determining for both catalysts (Delta G(22-25)*[double bond] kcal mol(-1)). The dissociative pathway starts with the dissociation of phosphane, which is rather facile (Delta G(298)* is approximately equal to 5-10 kcal mol(-1)). The resulting active species (L)Cl(2)Ru[double bond]CH(2) can coordinate ethene cis or trans to L. The cis addition is unfavorable and mechanistically irrelevant (Delta G(298)* is approximately equal to 21-25 kcal mol(-1)). The trans coordination is barrierless, and the rate-determining step in the subsequent catalytic cycle is either ring closure of the complex to yield the ruthenacyclobutane (catalyst I, Delta G(298)*=12 kcal mol(-1)), or the reverse reaction (catalyst II, ring opening, Delta G(298)*=10 kcal mol(-1)), that is, II is slightly more active than I. For both catalysts, the dissociative mechanism with trans olefin coordination is favored. The relative energies of the species on this pathway can be tuned by ligand variation, as seen in (PMe(3))(2)Cl(2)Ru[double bond]CH(2) (III), in which phosphane dissociation is impeded and olefin insertion is facilitated relative to I. The differences in calculated relative energies for the model catalysts I-III can be rationalized in terms of electronic effects. Comparisons with experiment indicate that steric effects must also be considered for real catalysts containing bulky substituents.     

受限于不同螺旋性的纳米碳管中水的分子动力学模拟

近年来将纳米碱米碳管引入到与生命过程息息相关的离子通道膜的研究逐渐成 为热点，而其中的关键就是要了解受限于膜孔道（碳管）中水分子的行为。采用分 子动力学模拟在300 K和1.01 * 10~5 Pa下对受限于（6，6）armchair型和（10， 0）zigzag型纳米碳管中的水进行了研究，得到了水分子在碳管中的局部密度分布 等静态性质以及水分子在碳管中的传递等动态性质，并对不同势能模型的模拟结果 作了比较。结果表明选择不同的势能模型并没有改变此体系的固有性质，即水分子 不仅能够进入到憎水性的（6，6）碳管中而且能形成一条稳定的由氢键相连的纵列 （single file），而且在管中以纵列的形式进行同歇传递。此外，碳管螺旋性对 受限水的静态性质影响不大但对动态性质则有一定程度的影响，水分子在（10，0 ）zigzag型碳管中的传递能力要强于在（6，6）armchair型碳管中的能力。     

Effect of quantum partial charges on the structure and dynamics of water in single-walled carbon nanotubes

In this work, using quantum partial charges, computed from 6-31G(**)B3LYP density functional theory, in molecular dynamics simulations, we found that water inside (6,6) and (10,0) single-walled carbon nanotubes with similar diameters but with different chiralities has remarkably different structural and dynamical properties. Density functional calculations indicate that tubes with different chiralities have significantly different partial charges at the ends of tubes. The partial charges at the ends of a (10,0) tube are around 4.5 times higher than those of a (6,6) tube. Molecular dynamics simulations with the partial charges show different water dipole orientations. In the (10,0) tube, dipole vectors of water molecules at the end of the tube point towards the water reservoir resulting in the formation of an L defect in the center region. This is not observed in the (6,6) tube where dipole vectors of all the water molecules inside the tube point towards either the top or the bottom water reservoir. The water diffusion coefficient is found to increase in the presence of the partial charges. Water in the partially charged (10,0) tube has a lower diffusion coefficient compared to that of in the partially charged (6,6) tube.     

Thermodynamic integration to predict host-guest binding affinities

An alchemical free energy method with explicit solvent molecular dynamics simulations was applied as part of the blind prediction contest SAMPL3 to calculate binding free energies for seven guests to an acyclic cucurbit-[n]uril host. The predictions included determination of protonation states for both host and guests, docking pose generation, and binding free energy calculations using thermodynamic integration. We found a root mean square error (RMSE) of 3.6 kcal mol(-1) from the reference experimental results, with an R(2) correlation of 0.51. The agreement with experiment for the largest contributor to this error, guest 6, is improved by 1.7 kcal mol(-1) when a periodicity-induced free energy correction is applied. The corrections for the other ligands were significantly smaller, and altogether the RMSE was reduced by 0.4 kcal mol(-1). We link properties of the host-guest systems during simulation to errors in the computed free energies. Overall, we show that charged host-guest systems studied here, initialized in unconfirmed docking poses, present a challenge to accurate alchemical simulation methods.     

Favorable pendant-amino metal chelation in VX nerve agent model systems

We have performed DFT computational studies [B3LYP, 6-31+G] to obtain metal ion coordination isomers of VX-Me [MeP(O)(OMe)(SCH2CH2NMe2)], a model of two of the most lethal nerve agents: VX [MeP(O)(OEt)(SCH2CH2N(iPr)2)] and Russian-VX [MeP(O)(OCH2CHMe2)(SCH2CH2N(Et)2)]. Our calculations involved geometry optimizations of the neutral VX-Me model as well as complexes with H+, Li+, Na+, K+, Be2+, Mg2+, and Ca2+ that yielded 2-8 different stable chelation modes for each ion that involved mainly mono- and bidentate binding. Importantly, our studies revealed that the [O(P),N] bidentate binding mode, long thought to be the active mode in differentiating the hydrolytic path of VX from other nerve agents, was the most stable for all ions studied here. Binding energy depended mainly on ionic size as well as charge, with binding energies ranging from 364 kcal mol(-1) for Be2+ to 33 kcal mol(-1) for K+. Furthermore, calculated NMR shifts for VX-Me correlate to experimental values of VX.     

Mechanism of the hydration of carbon dioxide: direct participation of H2O versus microsolvation

Thermochemical parameters of carbonic acid and the stationary points on the neutral hydration pathways of carbon dioxide, CO 2 + nH 2O --> H 2CO 3 + ( n - 1)H 2O, with n = 1, 2, 3, and 4, were calculated using geometries optimized at the MP2/aug-cc-pVTZ level. Coupled-cluster theory (CCSD(T)) energies were extrapolated to the complete basis set limit in most cases and then used to evaluate heats of formation. A high energy barrier of approximately 50 kcal/mol was predicted for the addition of one water molecule to CO 2 ( n = 1). This barrier is lowered in cyclic H-bonded systems of CO 2 with water dimer and water trimer in which preassociation complexes are formed with binding energies of approximately 7 and 15 kcal/mol, respectively. For n = 2, a trimeric six-member cyclic transition state has an energy barrier of approximately 33 (gas phase) and a free energy barrier of approximately 31 (in a continuum solvent model of water at 298 K) kcal/mol, relative to the precomplex. For n = 3, two reactive pathways are possible with the first having all three water molecules involved in hydrogen transfer via an eight-member cycle, and in the second, the third water molecule is not directly involved in the hydrogen transfer but solvates the n = 2 transition state. In the gas phase, the two transition states have comparable energies of approximately 15 kcal/mol relative to separated reactants. The first path is favored over in aqueous solution by approximately 5 kcal/mol in free energy due to the formation of a structure resembling a (HCO 3 (-)/H 3OH 2O (+)) ion pair. Bulk solvation reduces the free energy barrier of the first path by approximately 10 kcal/mol for a free energy barrier of approximately 22 kcal/mol for the (CO 2 + 3H 2O) aq reaction. For n = 4, the transition state, in which a three-water chain takes part in the hydrogen transfer while the fourth water microsolvates the cluster, is energetically more favored than transition states incorporating two or four active water molecules. An energy barrier of approximately 20 (gas phase) and a free energy barrier of approximately 19 (in water) kcal/mol were derived for the CO 2 + 4H 2O reaction, and again formation of an ion pair is important. The calculated results confirm the crucial role of direct participation of three water molecules ( n = 3) in the eight-member cyclic TS for the CO 2 hydration reaction. Carbonic acid and its water complexes are consistently higher in energy (by approximately 6-7 kcal/mol) than the corresponding CO 2 complexes and can undergo more facile water-assisted dehydration processes.