Sergey Gusarov

Diazonium-Derived Aryl Films on Gold Nanoparticles: Evidence for a Carbon–Gold Covalent Bond

Tailoring the surface chemistry of metallic nanoparticles is generally a key step for their use in a wide range of applications. There are few examples of organic films covalently bound to metal nanoparticles. We demonstrate here that aryl films are formed on gold nanoparticles from the spontaneous reduction of diazonium salts. The structure and the bonding of the film is probed with surface-enhanced Raman scattering (SERS). Extinction spectroscopy and SERS show that a nitrobenzene film forms on gold nanoparticles from the corresponding diazonium salt. Comparison of the SERS spectrum with spectra computed from density functional theory models reveals a band characteristic of a Au-C stretch. The observation of this stretch is direct evidence of a covalent bond. A similar band is observed in high-resolution electron energy loss spectra of nitrobenzene layers on planar gold. The bonding of these types of films through a covalent interaction on gold is consistent with their enhanced stability observed in other studies. These findings provide motivation for the use of diazonium-derived films on gold and other metals in applications where high stability and/or strong adsorbate-substrate coupling are required.

An MM/3D-RISM approach for ligand binding affinities.

We have modified the popular MM/PBSA or MM/GBSA approaches (molecular mechanics for a biomolecule, combined with a Poisson-Boltzmann or generalized Born electrostatic and surface area nonelectrostatic solvation energy) by employing instead the statistical-mechanical, three-dimensional molecular theory of solvation (also known as 3D reference interaction site model, or 3D-RISM-KH) coupled with molecular mechanics or molecular dynamics ( Blinov , N. ; et al. Biophys. J. 2010 ; Luchko , T. ; et al. J. Chem. Theory Comput. 2010 ). Unlike the PBSA or GBSA semiempirical approaches, the 3D-RISM-KH theory yields a full molecular picture of the solvation structure and thermodynamics from the first principles, with proper account of chemical specificities of both solvent and biomolecules, such as hydrogen bonding, hydrophobic interactions, salt bridges, etc. We test the method on the binding of seven biotin analogues to avidin in aqueous solution and show it to work well in predicting the ligand-binding affinities. We have compared the results of 3D-RISM-KH with four different generalized Born and two Poisson-Boltzmann methods. They give absolute binding energies that differ by up to 208 kJ/mol and mean absolute deviations in the relative affinities of 10-43 kJ/mol.

Plant Biomass Recalcitrance: Effect of Hemicellulose Composition on Nanoscale Forces that Control Cell Wall Strength

Efficient conversion of lignocellulosic biomass to second-generation biofuels and valuable chemicals requires decomposition of resilient plant cell wall structure. Cell wall recalcitrance varies among plant species and even phenotypes, depending on the chemical composition of the noncellulosic matrix. Changing the amount and composition of branches attached to the hemicellulose backbone can significantly alter the cell wall strength and microstructure. We address the effect of hemicellulose composition on primary cell wall assembly forces by using the 3D-RISM-KH molecular theory of solvation, which provides statistical-mechanical sampling and molecular picture of hemicellulose arrangement around cellulose. We show that hemicellulose branches of arabinose, glucuronic acid, and especially glucuronate strengthen the primary cell wall by strongly coordinating to hydrogen bond donor sites on the cellulose surface. We reveal molecular forces maintaining the cell wall structure and provide directions for genetic modulation of plants and pretreatment design to render biomass more amenable to processing.

Evaluation of the SCF Combination of KS-DFT and 3D-RISM-KH; Solvation Effect on Conformational Equilibria, Tautomerization Energies, and Activation Barriers

The effect of solvation on conformational equilibria, tautomerization energies, and activation barriers in simple SN2 reactions is reproduced by using the self-consistent field coupling of the Kohn-Sham density functional theory (KS-DFT) for electronic structure and the three-dimensional reference interaction site model with the closure approximation of Kovalenko and Hirata (3D-RISM-KH) for molecular solvation structure. These examples are used in order to validate the implementation of the 3D-RISM-KH method in the Amsterdam Density Functional package. The computations of the free energy difference in the trans/gauche conformational equilibrium for 1,2-dichloroethane in different solvents; the relative tautomerization free energy for cytosine, isocytosine, and guanine; and the free energy activation barrier for a CH3X-type (X = F, Cl, Br) SN2 reaction exhibit agreement with the experimental data. The method is also applied to the electronic and hydration structure of carbon single-wall nanotubes of different diameters, including the effect of water located in the inner space of the nanotubes. A comparison with continuum models of solvation (including COSMO) as well as with other more precise and computationally more expensive calculations is made to demonstrate the accuracy and predictive capability of the new KS-DFT/3D-RISM-KH method.

Computational and Experimental Study of the Structure, Binding Preferences, and Spectroscopy of Nickel(II) and Vanadyl Porphyrins in Petroleum

We present a computational exploration of five- and six-coordinate Ni(II) and vanadyl porphyrins, including prediction of UV-vis spectroscopic behavior and metalloporphyrin structure as well as determination of a binding energy threshold between strongly bound complexes that have been isolated as single crystals and weakly bound ones that we detect by visible absorption spectroscopy. The excited states are calculated using the tandem of the time-dependent density functional theory (TD-DFT) and the conductor-like polarizable continuum model (CPCM). The excited-state energies in chloroform solvent obtained by using two density functionals are found to correlate linearly with the experimental Soret and alpha-band energies for a known series of five-coordinate vanadyl porphyrins. The established linear correction allows simulation of the excited states for labile octahedral vanadyl porphyrins that have not been isolated and yields Soret and alpha-band bathochromic shifts that are in agreement with our UV-vis spectroscopic results. The PBE0 and PW91 functionals in combination with DNP basis set perform best for both structure and binding energy prediction. The reactivity preferences of Ni(II) and vanadyl porphyrins toward aromatic fragments of large petroleum molecules are explored by using the density functional theory (DFT). Analysis of electrostatic potentials and Fukui functions matching shows that axial coordination and hydrogen bonding are the preferred aggregation modes between vanadyl porphyrins and nitrogen-containing heterocycle fragments. This investigation improves our understanding on the cause for broadening of the Ni and V porphyrin Soret band in heavy oils. Our findings can be useful for the development of metals removal methods for heavy oil upgrading.

Ab initio study of ionic liquids by KS-DFT/3D-RISM-KH theory.

Properties of molecules solvated in ionic liquids (ILs) are strongly affected by solvent environment. For this reason, to give reliable results, ab initio calculations on solutes in ILs, including ions constituting ionic liquid itself, have to self-consistently account for the change of both electronic and classical solvation structure in ILs. Here, we study the electronic structure of the methyl-methylimidazolium ion in the bulk liquid of [mmim][Cl] by using the self-consistent field coupling of Kohn-Sham density functional theory and three-dimensional molecular theory of solvation (aka 3D-RISM) with the closure approximation of Kovalenko and Hirata. The KS-DFT/3D-RISM-KH method yields the 3D distribution of the IL solvent species around the [mmim] solute, underlying the most important peculiarities of this kind of systems such as the stacking interaction between neighboring cations, and reproduces the enhancement of the dipole moment resulting from the polarization of the cation by the solvent in a very good agreement with the results of an ab initio MD calculation. The KS-DFT/3D-RISM-KH method offers an accurate and computationally efficient procedure to perform ab initio calculations on species solvated in ionic liquids.

Molecular theory of solvation for supramolecules and soft matter structures: application to ligand binding, ion channels, and oligomeric polyelectrolyte gelators

We combine the statistical–mechanical 1D/3D-RISM-KH molecular theory of solvation with DFT electronic structure calculations and MD and coarse-grained DPD simulations, and apply them to study association phenomena in synthetic organic soft matter and biomolecular systems. This combined approach from electronic to molecular structure and coarse-graining allows us to address complex processes occurring in solution on very long timescales, such as protein–ligand binding, distributions of electrolyte solution species in ion channels, and oligomeric polyelectrolyte gelation. The statistics of rare events involving supramolecular solute and solvent is accounted for analytically within the 3D-RISM-KH molecular theory of solvation. The hybrid MD/3D-RISM-KH method for molecular dynamics of the biomolecule in the potential of mean force obtained with the molecular theory of solvation has been implemented in the Amber package. The 3D molecular theory of solvation also replaces MM/GB(PB)SA post-processing using empirical treatment of non-polar contributions with MM/3D-RISM-KH evaluation of the solvation thermodynamics. The 3D-RISM-KH theory accurately yields the solvation structure for biomolecular systems as large as the GroEL chaperonin complex, GLIC ion channel, and 3D maps of ligand binding affinity of antiprion compound to mouse PrPC prion protein at once without phenomenological approximations. We apply the DFT/1D-3D-RISM-KH/DPD multiscale approach to investigate the structural and dynamical properties and gelation ability of oligomeric polyelectrolyte gelators, towards understanding of the gelation mechanism.

Efficient treatment of solvation shells in 3D molecular theory of solvation

We developed a technique to decrease memory requirements when solving the integral equations of three‐dimensional (3D) molecular theory of solvation, a.k.a. 3D reference interaction site model (3D‐RISM), using the modified direct inversion in the iterative subspace (MDIIS) numerical method of generalized minimal residual type. The latter provides robust convergence, in particular, for charged systems and electrolyte solutions with strong associative effects for which damped iterations do not converge. The MDIIS solver (typically, with 2 × 10 iterative vectors of argument and residual for fast convergence) treats the solute excluded volume (core), while handling the solvation shells in the 3D box with two vectors coupled with MDIIS iteratively and incorporating the electrostatic asymptotics outside the box analytically. For solvated systems from small to large macromolecules and solid–liquid interfaces, this results in 6‐ to 16‐fold memory reduction and corresponding CPU load decrease in MDIIS. We illustrated the new technique on solvated systems of chemical and biomolecular relevance with different dimensionality, both in ambient water and aqueous electrolyte solution, by solving the 3D‐RISM equations with the Kovalenko–Hirata (KH) closure, and the hypernetted chain (HNC) closure where convergent. This core–shell‐asymptotics technique coupling MDIIS for the excluded volume core with iteration of the solvation shells converges as efficiently as MDIIS for the whole 3D box and yields the solvation structure and thermodynamics without loss of accuracy. Although being of benefit for solutes of any size, this memory reduction becomes critical in 3D‐RISM calculations for large solvated systems, such as macromolecules in solution with ions, ligands, and other cofactors.

Electronic structure, binding energy, and solvation structure of the streptavidin-biotin supramolecular complex: ONIOM and 3D-RISM study.

We studied the electronic structure of the binding site of the streptavidin-biotin complex by using the ONIOM method at the HF/STO-3G:UFF level and obtained the solvation structure of the complex by using the statistical-mechanical, three-dimensional molecular theory of solvation (aka three-dimensional reference interaction site model, 3D-RISM-KH). All the streptavidin residues located within 3 A of the biotin residue were included in the quantum mechanical (QM) layer. In total, 16 residues including biotin with 274 atoms were in the QM layer, in which five residues are responsible for the hydrophobic interactions and nine residues for the hydrogen-bonding/electrostatic interaction with biotin. We found a geometry change of the urea moiety of the biotin bound in the network of van der Waals and polar interactions. Compared to the isolated biotin, the bridging C-C bond of the biotin urea moiety in the binding site increases in length as a result of the pi-sigma interaction with the surrounding streptavidin Trp residues. This extends the previous picture of the geometry change from the ureido group to the whole bicyclic urea moiety. We have evaluated the performance of 15 density functional methods and 11 basis sets by single point calculation for the binding energy of the optimized cooperative binding complex structure. Closest to the experimental value of 18.3 kcal/mol is the binding free energy of 19.6 kcal/mol obtained for the AN model at B3LYP/6-31G(d):UFF//HF/STO-3G:UFF level. The hybrid DFT methods with enhanced assessment for nonbonded interactions such as PBE1PBE, MPW1B95, and MPWB1K can also give accurate binding energy with the use of diffuse functionals (i.e., mPWB1K/6-31+G(d)). The 3D hydration structure of the unliganded streptavidin and the streptavidin-biotin complex obtained by using the 3D-RISM-KH molecular theory of solvation shows there is one immobilized water molecule at the biotin urea moiety, acting as a water bridge between the sulfur and the nitrogen of the NH group close to Ser45. This suggests that, in the docking process, biotin replaces six of the seven water molecules attached to the unliganded streptavidin binding site, and one remaining water molecule is squeezed into the gap between the Btn, Tyr43, Ser45, Trp92, and Trp79 residues in the binding pocket.

Supramolecular Interactions in Secondary Plant Cell Walls: Effect of Lignin Chemical Composition Revealed with the Molecular Theory of Solvation

Plant biomass recalcitrance, a major obstacle to achieving sustainable production of second generation biofuels, arises mainly from the amorphous cell-wall matrix containing lignin and hemicellulose assembled into a complex supramolecular network that coats the cellulose fibrils. We employed the statistical-mechanical, 3D reference interaction site model with the Kovalenko-Hirata closure approximation (or 3D-RISM-KH molecular theory of solvation) to reveal the supramolecular interactions in this network and provide molecular-level insight into the effective lignin-lignin and lignin-hemicellulose thermodynamic interactions. We found that such interactions are hydrophobic and entropy-driven, and arise from the expelling of water from the mutual interaction surfaces. The molecular origin of these interactions is carbohydrate-π and π-π stacking forces, whose strengths are dependent on the lignin chemical composition. Methoxy substituents in the phenyl groups of lignin promote substantial entropic stabilization of the ligno-hemicellulosic matrix. Our results provide a detailed molecular view of the fundamental interactions within the secondary plant cell walls that lead to recalcitrance.