Rajiv Berry

Chemistry of aqueous silica nanoparticle surfaces and the mechanism of selective peptide adsorption

Control over selective recognition of biomolecules on inorganic nanoparticles is a major challenge for the synthesis of new catalysts, functional carriers for therapeutics, and assembly of renewable biobased materials. We found low sequence similarity among sequences of peptides strongly attracted to amorphous silica nanoparticles of various size (15-450 nm) using combinatorial phage display methods. Characterization of the surface by acid base titrations and zeta potential measurements revealed that the acidity of the silica particles increased with larger particle size, corresponding to between 5% and 20% ionization of silanol groups at pH 7. The wide range of surface ionization results in the attraction of increasingly basic peptides to increasingly acidic nanoparticles, along with major changes in the aqueous interfacial layer as seen in molecular dynamics simulation. We identified the mechanism of peptide adsorption using binding assays, zeta potential measurements, IR spectra, and molecular simulations of the purified peptides (without phage) in contact with uniformly sized silica particles. Positively charged peptides are strongly attracted to anionic silica surfaces by ion pairing of protonated N-termini, Lys side chains, and Arg side chains with negatively charged siloxide groups. Further, attraction of the peptides to the surface involves hydrogen bonds between polar groups in the peptide with silanol and siloxide groups on the silica surface, as well as ion-dipole, dipole-dipole, and van-der-Waals interactions. Electrostatic attraction between peptides and particle surfaces is supported by neutralization of zeta potentials, an inverse correlation between the required peptide concentration for measurable adsorption and the peptide pI, and proximity of cationic groups to the surface in the computation. The importance of hydrogen bonds and polar interactions is supported by adsorption of noncationic peptides containing Ser, His, and Asp residues, including the formation of multilayers. We also demonstrate tuning of interfacial interactions using mutant peptides with an excellent correlation between adsorption measurements, zeta potentials, computed adsorption energies, and the proposed binding mechanism. Follow-on questions about the relation between peptide adsorption on silica nanoparticles and mineralization of silica from peptide-stabilized precursors are raised.

Adsorption mechanism of single amino acid and surfactant molecules to Au {111} surfaces in aqueous solution: design rules for metal-binding molecules

The adsorption mechanism of twenty amino acids and four surfactants was examined on a {111} surface of gold in dilute aqueous solution using molecular dynamics simulation with a broadly applicable intermolecular potential CHARMM–METAL. All molecules are attracted to the surface between −3 and −26 kcal mol−1. The adsorption strength correlates with the degree of coordination of polarizable atoms (O, N, C) to multiple epitaxial sites. Therefore, the molecular size and geometry rather than the specific chemistry determine the adsorption energy. Large molecules with planar sp2 hybridized groups (Arg, Trp, Gln, Tyr, Asn, and PPh3) adsorb most strongly, followed by molecules with polar sp3 hybridized groups, and short molecules with sp3 hybridized alkyl groups exhibit least attraction. Conformationally flexible, extended molecules such as hexadecyltrimethylammonium bromide (CTAB) also showed significant attraction to the metal surface related to accommodation in epitaxial grooves and coordination with numerous epitaxial sites. Computational results are consistent with combinatorial binding experiments, observations in the growth and stabilization of metal nanoparticles, and ab initio data. The mechanism of adsorption conforms to soft epitaxy observed for peptides on metal surfaces (H. Heinz et al., J. Am. Chem. Soc., 2009, 131, 9704) and enables the de novo design of molecules for binding to a given metal surface. In addition to soft epitaxy, contributions to adsorption are possible by covalent bonding and induced charges.

Molecular dynamics simulation study of norbornene–POSS polymers

Abstract Atomistic molecular dynamics simulations have been used to delineate the effects of introducing polyhedral oligomeric silsesquioxane (POSS) moieties substituted by cyclopentyl and cyclohexyl rings as pendant groups on polynorbornene. Simulations were also performed on polynorbornene for comparison. Calculated volume–temperature behavior and X-ray scattering profiles matched well with experimental results. Most importantly, the effects of incorporating the POSS moieties into the polymer have been identified via simulations. These were judged on the basis of the increase in the glass transition temperature, retardation of the chain dynamics and improvements in the calculated elastic tensile, bulk and shear moduli of the POSS containing polymers compared to the norbornene homopolymer. The most important conclusion from the study is that aggregation of the POSS moieties is not required for the beneficial effects to be realized. Indeed, the simulations show that there is no tendency for aggregation to occur among the POSS moieties if they are well dispersed to begin with over the time scale of the simulation. Packing features are delineated with the aid of intermolecular site–site radial distribution functions. In addition, the mean squared displacement of the POSS moieties in the polymer matrix was found to be very small at all temperatures leading to a slowing of the segmental dynamics of the polymer chain, and thereby imparting the macroscopically observed stiffness. It is reasoned that the chief source of reinforcement arises from the POSS moieties behaving as strong anchor points in the polymeric matrix. This has more to do with the ponderous nature of these moieties versus any specific intermolecular interactions.

Derivation of class II force fields. VIII. Derivation of a general quantum mechanical force field for organic compounds

A class II valence force field covering a broad range of organic molecules has been derived employing ab initio quantum mechanical “observables.” The procedure includes selecting representative molecules and molecular structures, and systematically sampling their energy surfaces as described by energies and energy first and second derivatives with respect to molecular deformations. In this article the procedure for fitting the force field parameters to these energies and energy derivatives is briefly reviewed. The application of the methodology to the derivation of a class II quantum mechanical force field (QMFF) for 32 organic functional groups is then described. A training set of 400 molecules spanning the 32 functional groups was used to parameterize the force field. The molecular families comprising the functional groups and, within each family, the torsional angles used to sample different conformers, are described. The number of stationary points (equilibria and transition states) for these molecules is given for each functional group. This set contains 1324 stationary structures, with 718 minimum energy structures and 606 transition states. The quality of the fit to the quantum data is gauged based on the deviations between the ab initio and force field energies and energy derivatives. The accuracy with which the QMFF reproduces the ab initio molecular bond lengths, bond angles, torsional angles, vibrational frequencies, and conformational energies is then given for each functional group. Consistently good accuracy is found for these computed properties for the various types of molecules. This demonstrates that the methodology is broadly applicable for the derivation of force field parameters across widely differing types of molecular structures.

Simulations of Peptide-Graphene Interactions in Explicit Water

The interaction of graphene with biomolecules has a variety of useful applications. In particular, graphitic surfaces decorated with peptides are being considered for high performance biochemical sensors. The interaction of peptides with graphene can also provide insight into the binding behavior of larger biomolecules. In this investigation, we have computed the binding enthalpies of a series of GXG tripeptides with graphene using classical molecular dynamics. Explicit water molecules were included to capture the effect of solvent. Of the twenty amino acid residues examined (X in GXG), arginine, glutamine, and asparagine exhibit the strongest interactions with graphene. Analysis of the trajectories shows that the presence of graphene affects the peptide conformation relative to its conformation in solution. We also find that the peptides favor the graphene interface predominantly due to the influence of the solvent, with hydrophilic residues binding more strongly than hydrophobic residues. These results demonstrate the need to include explicit solvent atoms when modeling peptide-graphene systems to mimic experimental conditions. Furthermore, the scheme outlined herein may be widely applicable for the determination and validation of surface interaction parameters for a host of molecular fragments using a variety of techniques, ranging from coarse-grained models to quantum mechanical methods.

Impact of polymer structure and confinement on the kinetics of Zdol 4000 bonding to amorphous‐hydrogenated carbon

The bonding of molecularly‐thin (10 Å) Zdol 4000 films to amorphous, hydrogenated carbon (CHx) was investigated as a function of the Zdol structure, i.e., the ratio of the perfluoromethylene oxide (C1) to perfluoroethylene oxide (C2) monomer units in the backbone. The influence of the C1/C2 ratio on the intrinsic mobility of the Zdol polymer was also investigated by computing the energetic barriers to internal rotation about the C–O and C–C bonds in model compounds by both ab initio and molecular mechanics methods. The calculations indicate that increasing the C1/C2 ratio increases the relative flexibility of the Zdol polymer. The kinetic results demonstrate that the rate at which submonolayer Zdol films bond to CHx is non‐classical (time‐dependent) regardless of the Zdol chain stiffness. The Zdol bonding rate can best be described by a kinetic equation of the form, dB/dt=k(t)A, where the rate coefficient, k(t) can be expressed as a power function in time: k(t)= kBt-h. The values of the initial bonding rate constant, kB, and the functional form of the time dependence, t-h, are both strongly dependent on the Zdol backbone flexibility. The magnitude of the initial bonding rate constants generally increase with increasing Zdol chain mobility. A discontinuous change in both the magnitude of kB and the functional form of the time dependence is, however, observed at 64°C when the C1/C2 ratio is increased from 0.97 to 1.08. The bonding rate coefficient scales as t-0.5 for the relatively rigid Zdol backbone structures with C1/C2 < 1, while a t-1.0 time‐dependent bonding rate is observed for the more flexible Zdol backbones with C1/C2 < 1. The initial rate constant, kB, also changes abruptly near C1/C2 ≈ 1, with kB of the flexible Zdol chains (samples with C1/C2) being approximately an order of magnitude greater than the more rigid chains (C1/C2 < 1). These results indicate that the physical state of the confined Zdol film can be either liquidlike or solidlike depending upon the molecular stiffness of the backbone employed. The t-0.5 time‐dependent bonding rate is shown to be consistent with a one‐dimensional, diffusion‐limited reaction from a solidlike Zdol structure, whereas the t-1.0 bonding rate results when bonding occurs from a liquidlike Zdol film structure. The temperature dependence of the Zdol 4000 bonding rate coefficient for the Zdol backbone characterized by C1/C2 = 0.97 (solidlike at T = 64°C) was found to undergo a transition from a t-0.5 time dependence for T < 150°C, to a t-1.0 time dependence at T > 180. This transition occurs over relatively narrow temperature range (150 < T < 180°C) and is attributed to a 2D melting of the confined Zdol film.

A computational study of bond dissociation enthalpies and hydrogen abstraction energy barriers in model urethanes

Ab initio energies obtained at the MP2/6-311+G(3df,2p)//MP2/6-31G(d) level of theory were employed using isodesmic reactions to compute C–H and N–H room temperature bond dissocation enthalpies (BDEs), for the various hydrogens in a series of model alkyl urethanes (carbamates). It was found that the BDEs [in kJ/mol] vary in the order α-C(N) [402]<α-C(O) [417]<β-C(N) [425]≈β-C(O)≪N–H [465] (where α-C(N) refers to the α-carbon on the nitrogen side of the functional group, etc.). The unusually high N–H BDE was found to result from the loss of stabilization via conjugation with the carbonyls π-electrons in the radical. The low C–H bond strengths on both the α-carbons were attributed to resonance stabilization of the radical center by the nitrogen or oxygen lone-pair electrons. These results, in which it is predicted that the C–H on the α-C(N) is the weakest bond, are in accordance with the results of a recent experimental study on photodecomposition of polyurethanes, where it was concluded that initial radical attack is at this site. It was also found that C–H BDEs on the α-carbons increase when a methyl group is added at this position. This trend was rationalized on the basis of lessened resonance stabilization of the branched radicals. Transition state structures and energies, and reaction energy barriers, ΔE0‡, were computed for hydrogen abstraction reactions by a methyl radical, RH+CH3→R+CH4, for the C–H and N–H bonds in the four model urethane. There was an excellent correlation between ΔE0‡ and BDE for all hydrogens on the linear alkyl urethanes. However, energy barriers for the removal of hydrogen atoms from the α-carbons of the two branched urethanes lay significantly below the curve established by the linear species. This observation was explained on the basis of comparative structures of the parent compounds, transition states and radicals. As ΔE0‡[α-C(N)] was lower for the branched than the linear urethane, it was concluded that one should not expect any significant enhancement of the photochemical stability of branched aliphatic polyurethane coatings relative to their linear counterparts.

A computational study of chlorofluoro-methyl radicals

Chorine- and fluorine-containing methyl radicals have been investigated by ab initio methods. Geometries and vibrational frequencies were derived with quadratic configuration methods at the QCISD/6-311G(d,p) level of theory, and energies via QCISD(T)/6-311+G(3df,2p) and Gaussian 3 theory. Anharmonicity of the out of plane bending mode was taken into account by numerical integration of the Schrodinger equation with a potential derived from a relaxed scan of this mode. The results are in good accord with experimental data where available. For the radicals CHF2, CF3, CH2Cl, CHCl2, and CCl3, we compute ΔfH2980 values of −241.2, −465.9, 117.0, 91.1, and 72.2 kJ mol−1, respectively, which agree with well-established experimental values to within 2.2 kJ mol−1. For the more poorly characterized molecules CH2F, CHClF, CClF2, and CCl2F we compute ΔfH2980 values of −29.0, −63.8, −274.7, and −94.3 kJ mol−1, respectively, with recommended confidence limits of ±4.1 kJ mol−1.

Computation of the binding free energy of peptides to graphene in explicit water

The characteristic properties of graphene make it useful in an assortment of applications. One particular application--the use of graphene in biosensors--requires a thorough understanding of graphene-peptide interactions. In this study, the binding of glycine (G) capped amino acid residues (termed GXG tripeptides) to trilayer graphene surfaces in aqueous solution was examined and compared to results previously obtained for peptide binding to single-layer free-standing graphene [A. N. Camden, S. A. Barr, and R. J. Berry, J. Phys. Chem. B 117, 10691-10697 (2013)]. In order to understand the interactions between the peptides and the surface, binding enthalpy and free energy values were calculated for each GXG system, where X cycled through the typical 20 amino acids. When the GXG tripeptides were bound to the surface, distinct conformations were observed, each with a different binding enthalpy. Analysis of the binding energy showed the binding of peptides to trilayer graphene was dominated by van der Waals interactions, unlike the free-standing graphene systems, where the binding was predominantly electrostatic in nature. These results demonstrate the utility of computational materials science in the mechanistic explanation of surface-biomolecule interactions which could be applied to a wide range of systems.

Ab initio investigation of substituent effects on bond dissociation enthalpies in siloxanes and silanols

Silicon–oxygen Bond Dissociation Enthalpies (BDEs) were computed at the Gaussian-2 level of theory (using isodesmic reactions) for a series of substituted siloxanes and silanols, SiRnH3−nOSiH3 and SiRnH3−nOH, R=F, Cl, Br, OH, CH3. If was found that all substituents induce substantial increases in the bond strengths of the adjacent Si–O bonds. The magnitude of the effect roughly parallels the substituent electronegativity, and can be explained on the basis of an inductive increase of the bond polarity. Three of the substituents, fluorine, chlorine and hydroxyl groups, also cause relatively large increases in the dissociation enthalpies of the remote silicon–oxygen bond in the siloxanes. This latter effect was found to correlate negatively with Si–O bond length variations in the siloxy radicals. This correlation provides evidence that the bond enthalpy increases of the remote silicon–oxygen bonds arises from either inductive effects or π-backbonding, either of which would destabilize the radical center.