Effect of the peptide secondary structure on the peptide amphiphile supramolecular structure and interactions

Bottom-up fabrication of self-assembled nanomaterials requires control over forces and interactions between building blocks. We report here on the formation and architecture of supramolecular structures constructed from two different peptide amphiphiles. Inclusion of four alanines between a 16-mer peptide and a 16 carbon long aliphatic tail resulted in a secondary structure shift of the peptide headgroups from α helices to β sheets. A concomitant shift in self-assembled morphology from nanoribbons to core-shell worm-like micelles was observed by cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM). In the presence of divalent magnesium ions, these a priori formed supramolecular structures interacted in distinct manners, highlighting the importance of peptide amphiphile design in self-assembly.     

Vibrational spectral signatures of peptide secondary structures: N-methylation and side chain hydrogen bond in cyclosporin A

Molecular dynamics simulations are performed to explore important conformations of cyclosporin A, an immunosuppressive cyclic undecapeptide drug, in different media including gas-phase, chloroform, and acetonitrile. Density functional theory calculations are used to refine the low-lying conformers and to predict their infrared and vibrational circular dichroism spectra. Vibrational spectral signatures in the important amide II, I, and A regions are identified for typical peptide secondary structures including β-turn (type II' or I), antiparallel β-sheet (flat or twisted), inverse γ-turn, N-methylated peptide bond, and side chain H-bond. New insights into the spectral signatures of secondary structures especially with N-methylation and side chain hydrogen bond are provided, which can be very useful for further peptide conformation analysis in general.     

Many-orbital cluster expansion for the exchange-repulsion energy in the interaction of closed-shell systems

The energy of exchange repulsion between two closed-shell systems described by determinantal wave functions has been represented as a sum of contributions arising from the interaction of two, three and four orbitals at a time. These contributions have been calculated for the interaction of two neon atoms. It has been found that in the van der Waals minimum region the two-orbital components are of secondary importance and that about 90% of the total exchange energy originates from the three-orbital interactions ofL-shell electrons. The four-orbital as well as the double-exchange terms have been found negligible. The approximate algorithms for evaluation of the exchange repulsion energy have been tested and discussed.This work was partly supported by the Polish Academy of Sciences within the project MR-I.9.     

NQR and NMR study of hydrogen bonding interactions in anhydrous and monohydrated guanine cluster model: A computational study

In this paper extensive systematic computational study has been carried out to justify hydrogen bonding interactions and their influence on the oxygen, nitrogen and hydrogen NQR and NMR parameters of the anhydrous and monohydrated guanine crystal structures at two different levels, B3LYP and MP2, using 6-311++G** and D95** basis sets. These theoretical data have been compared with experimental NMR and NQR measurements. For further investigation, results of cluster calculation have been compared with that of a single molecule. Our theoretical NQR and NMR parameters of ¹⁷O, ¹⁵N and ²H atoms of anhydrous and monohydrated guanine exhibited extreme sensitivity to electron distribution around mentioned nuclei caused by cooperative influences of various types of hydrogen bonding interactions. Fortunately, our calculated isotropic shielding values and CS tensors for the ¹⁷O and ¹⁵N nuclei as well as obtained ¹⁴N-NQR parameters are in excellent agreement with experimental data. Therefore, we can undoubtedly conclude that for anhydrous and monohydrated guanine tetrameric clusters including intermolecular interactions, our theoretical estimates are in better agreement with observed experimental values than those in which these interactions have been ignored.     

A closed-shell coupled-cluster treatment of the Breit-Pauli first-order relativistic energy correction

First-order relativistic corrections to the energy of closed-shell molecular systems are calculated, using all terms in the two-component Breit-Pauli Hamiltonian. In particular, we present the first implementation of the two-electron Breit orbit-orbit integrals, thus completing the first-order relativistic corrections within the two-component Pauli approximation. Calculations of these corrections are presented for a series of small and light molecules, at the Hartree-Fock and coupled-cluster levels of theory. Comparisons with four-component Dirac-Coulomb-Breit calculations demonstrate that the full Breit-Pauli energy corrections represent an accurate approximation to a fully relativistic treatment of such systems. The Breit interaction is dominated by the spin-spin interaction, the orbit-orbit interaction contributing only about 10% to the total two-electron relativistic correction in molecules consisting of light atoms. However, the relative importance of the orbit-orbit interaction increases with increasing nuclear charge, contributing more than 20% in H(2)S.     

Basicity of bisperhalophenyl aurates toward closed-shell metal ions: metallophilicity and additional interactions

The interaction of bisperhalophenyl aurates [AuR₂]^? (R?=?C₆F₅, C₆F₃Cl₂, and C₆Cl₅) with the closed-shell Ag⁺, Cu⁺, and Tl⁺ ions has been studied theoretically and compared with the experimentally known X-ray diffraction crystal structures. Initially, the aurates have been fully optimized at MP2 level of theory in a D _2h symmetry. The analysis of the basicity of the three aurates [AuR₂]^? (R?=?C₆F₅, C₆F₃Cl₂ and C₆Cl₅) against Ag⁺ ions in a C _2v symmetry has been calculated in point-by-point bsse-corrected interaction energy analysis at HF and MP2 levels of theory. Taking into account the experimental observation of additional interactions between the heterometals and C _ipso atoms at the perhalophenyl rings or halogen atoms at the ortho position of the perhalophenyl rings, dinuclear models of the type [AuR₂]^?···Ag⁺ (R?=?C₆Cl₅, and C₆F₅); [AuR₂]^?···Cu⁺ (R?=?C₆F₅, and C₆Cl₅) and [AuR₂]^?···Tl⁺ (R?=?C₆F₅, and C₆Cl₅) with a C _2v , C ₂ , and C _s symmetries have been optimized at DFT-B3LYP level. The interaction energies have been computed through bsse-corrected single point HF and MP2 calculations. The energy stabilization provided and the heterometal preference have been analyzed and compared with the experimental results.     

A scattering study on intermicellar interactions and structures of polymeric micelles

The micellar structure is usually considered to be composed of a hard sphere (liquid) core and a heavily solvated corona. Therefore, the correction for intermicellar interactions at finite concentrations can be relatively complicated. In this article, small-angle neutron scattering of a copolymer, known as Pluronic L64 (PEO₁₃PPO₃₀PEO₁₃), in o-xylene in the presence of D₂O is used to demonstrate that, based on the hard sphere approximation, intermicellar interactions can be corrected by representing the micellar size as having an equivalent hard sphere radius. The procedure remains valid even if the micellar shape becomes asymmetric, with axial ratios of 3 ? 4. For the present system, the equivalent hard sphere radius corresponds to the micellar core radius plus one-half of the micellar shell thickness. With the equivalent hard sphere approach, the scattering behavior of the micelle could be described by using a core-shell structure. © 1994 John Wiley & Sons, Inc.     

Perturbed structures generated using coordinates derived from compliance constants in internal vibrations for QTAIM dual functional analysis: Intrinsic dynamic nature of interactions

Perturbed structures for QTAIM dual functional analysis (QTAIM‐DFA) are proposed to generate using the coordinates corresponding to the compliance force constants in internal vibrations (CIV). In QTAIM‐DFA, total electron energy densities H_b( r _c) are plotted versus H_b( r _c) – V_b( r _c)/2 at bond critical points (BCPs) of interactions in question, where V_b( r _c) are potential energy densities at BCPs. Each plot of an interaction based on the data from both perturbed structures and fully optimized one takes the form (θ_p, κ_p), where θ_p corresponds to the tangent line of the plot and κ_p is the curvature. The θ_p values evaluated with CIV are equal to those obtained by partial optimizations with the interaction distance in question being fixed suitably, within the calculation errors. Very high applicability of CIV is demonstrated to generate the perturbed structures for QTAIM‐DFA. Dynamic nature of interactions based on (θ_p, κ_p) with CIV is called “intrinsic dynamic nature of interactions.”     

Probing the competition between secondary structures and local preferences in gas phase isolated peptide backbones

Combining laser desorption with a supersonic expansion together with the selectivity of IR/UV double resonance spectroscopy makes it possible to isolate and characterise the gas phase of remarkable backbone conformations of short peptide chains mimicking protein segments. A systematic bottom-up approach involving a conformer-specific IR study of peptide sequences of increasing sizes has enabled us to map the spectral signatures of the intramolecular interactions, which shape the peptide backbone, in particular H-bonds. The precise data collected are directly comparable to the most sophisticated quantum chemistry calculations of these species and therefore constitute a stringent test for the theoretical methods used. One-residue chains reveal the local conformational preference of the backbone and its dependence upon the nature of the residue. The investigation of longer chains provides evidence for a competition between simple successions of local conformational preferences along the chain and more folded structures, in which a new H-bonding network, involving distant H-bonding sites along the backbone, takes place. From three residues, the issue of helical folding can also be addressed. The present review of the gas phase literature data emphasizes the observation of remarkable secondary structures of biology, including short segments of beta-strands, gamma- and beta-turns, combinations of turns, including a 3(10) helix. It also provides evidence for the flexibility of the peptide chains, i.e., a critical influence of rather minor interactions (like side-chain/backbone interactions) on the conformational stability. Finally, the paper will discuss future promising directions of the present approach.     

A theoretical study of electronic structures and intermolecular magnetic interactions for spiro-biphenalenyls

In order to inquire into the mechanism of the change in the magnetism of spiro-biphenalnyls, intermolecular magnetic interaction has been investigated in terms of the effective exchange integral of the Heisenberg model for dimeric pairs of diethyl-substituted spiro-biphenalenyl. Variation of the magnetic interaction with respect to temperature has been evaluated for X-ray crystallographic structures at several temperature points by Kohn–Sham hybrid-DFT. The intermolecular magnetic interactions have been calculated for the π-dimers to be antiferromagnetic at each temperature, which has decreased by approximately 30% in the magnitude from 100 to 173 K. In addition, the interactions have been almost none at 100 and 173 K except for one pair and the remaining pair had ferromagnetic interaction. Therefore, it has been found that the change in their magnetism is understood by the formation of a ferromagnetic dimer-pair at 173 K. Moreover, the natural orbital analysis for the electronic structure of diethyl-substituted spiro-biphenelenyl has shown our solutions are essentially identified to Haddon’s proposal in terms of the valence bond picture.     

Protonolysis of the Hg-C bond of chloromethylmercury and dimethylmercury. A DFT and QTAIM study

Possible mechanisms for degrading chloromethylmercury (CH(3)HgCl) and dimethylmercury [(CH3)2Hg] involving thiol and ammonium residues were investigated by DFT and atoms-in-molecules (QTAIM) calculations. Using H2S and HS- as models for thiol and thiolate groups RSH and RS-, respectively, we obtained transition states and energy barriers for possible decomposition routes to Hg(SH)2 based on a model proposed by Moore and Pitts (Moore, M. J.; Distefano, M. D.; Zydowsky, L. D.; Cummings, R. T.; Walsh, C. T. Acc. Chem. Res. 1990, 23, 301. Pitts, K. E.; Summers, A. O. Biochemistry 2002, 41, 10287). Demethylation was found to be a multistep process that involved initial substitution of Cl- by RS-. We found that successive coordination of Hg with thiolates leads to increased negative charge on the methyl group and facilitates the protonolysis of the Hg-C bond by H-SH. This was also found to be the case for (CH3)2Hg. We found that NH4(+) readily protonolyzes the Hg-C bond of these thiolate complexes, suggesting that ammonium residues of protonated amino acids might also act as effective proton donors.     

Hydrogen-bonding interactions in peptide nucleic acid and deoxyribonucleic acid: a comparative study

Peptide nucleic acid (PNA) is a synthetic analogue of deoxyribonucleic acid (DNA) capable of tightly binding to itself and DNA with high specificity. Using hybrid density functional methods, hydrogen-bond (H-bond) strengths have been evaluated for isolated Watson-Crick base pairs, PNA base pairs, and charged as well as neutral DNA base pairs. Heterogeneous base pairs of PNA with charged and neutral DNA have also been investigated. The competing effects of short-range H-bonding and long-range Coulombic repulsions in charged DNA base pairs have been analyzed. Polarizable continuum models have been employed to evaluate solvation effects on the binding energies.     

On the electronic origin of strain energy: QTAIM study of perfluorocycloalkanes

The strain energies (SE) of the five smallest perfluorocycloalkanes (c-CnF2n; n=3, 4, 5, 6, and 7) were calculated by means of several homodesmotic processes using B3LYP/6-31++G(d,p) optimized molecular energies. These values were compared with the energy difference between the linear and cyclic CF2 groups calculated by means of the quantum theory of atoms in molecules (QTAIM) applied on charge densities obtained at the same computational level. The differences between the values computed with both methods vary from 255 (n=3) to 629 (n=7) kJ mol-1. These differences arise because QTAIM-computed SE contain the energy involved in opening the ring to give rise to nearly transferable central CF2 fragments of linear perfluoroalkanes, whereas homodesmotic energies contain energy terms corresponding to transformation of nontransferable linear CF2 fragments and a ring-opening energy, which depending on the process, transforms CF2 cyclic compounds into nearly transferable or nontransferable linear CF2 groups.     

Aromatic-aromatic interactions in crystal structures of helical peptide scaffolds containing projecting phenylalanine residues

Aromatic-aromatic interactions between phenylalanine side chains in peptides have been probed by the structure determination in crystals of three peptides: Boc-Val-Ala-Phe-Aib-Val-Ala-Phe-Aib-OMe, I; Boc-Val-Ala-Phe-Aib-Val-Ala-Phe-Aib-Val-Ala-Phe-Aib-OMe, II; Boc-Aib-Ala-Phe-Aib-Phe-Ala-Val-Aib-OMe, III. X-ray diffraction studies reveal that all three peptides adopt helical conformations in the solid state with the Phe side chains projecting outward. Interhelix association in the crystals is promoted by Phe-Phe interactions. A total of 15 unique aromatic pairs have been characterized in the three independent crystal structures. In peptides I and II, the aromatic side chains lie on the same face of the helix at i/i + 4 positions resulting in both intrahelix and interhelix aromatic interactions. In peptide III, the Phe side chains are placed on the opposite faces of the helix, resulting in exclusive intermolecular aromatic interactions. The distances between the centroids of aromatic pair ranges from 5.11 to 6.86 A, while the distance of closest approach of ring carbon atoms ranges from 3.27 to 4.59 A. Examples of T-shaped and parallel-displaced arrangements of aromatic pairs are observed, in addition to several examples of inclined arrangements. The results support the view that the interaction potential for a pair of aromatic rings is relatively broad and rugged with several minima of similar energies, separated by small activation barriers.     

Role of donor and secondary interactions in the structures and thermal properties of alkaline-earth and rare-earth metal pyrazolates

The addition of neutral coligands to reduce the aggregation and improve the volatility of potential heavy alkaline-earth metal chemical vapor deposition (CVD) precursors has typically resulted in liberation of the coligand upon heating. A new series of dinuclear alkaline-earth and rare-earth metal pyrazolates, bis[bis(3,5-di-tert-butylpyrazolato)(tetrahydrofuran)calcium] (1), bis[bis(3,5-di-tert-butylpyrazolato)(tetrahydrofuran)strontium] (2), and bis[bis(3,5-di-tert-butylpyrazolato)bis(tetrahydrofuran)barium] (3), have been obtained from our previous donor-free oligonuclear complexes [{M(3,5-tBu2pz)2}n] (5, M = Ca, n = 3; 6, M = Sr, n = 4; 7, M = Ba, n = 6) by treatment with tetrahydrofuran (THF). Compounds 1-3, as well as the europium analogue bis[bis(3,5-di-tert-butylpyrazolato)(tetrahydrofuran)europium(II)] (4), can also be prepared by direct reaction of the metals and pyrazole in THF and anhydrous liquid ammonia. Recrystallization from hexane led to single crystals of 2-4, while the powder diffraction pattern of 1 revealed it to be isostructural with the previously published bis[bis(3,5-di-tert-butylpyrazolato)(tetrahydrofuran)ytterbium(II)] (8), providing important insight into differences and similarities between the two groups of metals. Detailed structural analysis of the compounds reveals secondary interactions including pi-bonding and agostic interactions, which are considered essential in stabilizing the metal complexes. The direct comparison of structural features and thermal properties (as evaluated by thermogravimetric analysis and sublimation studies) of the donor-free oligonuclear and the donor-containing dinuclear species offers a better understanding of the role of donors and secondary interactions.     

Twisting of conjugated oligomers and polymers: case study of oligo- and polythiophene

Interring twisting (change in the dihedral angle between conjugated rings) of polythiophene was studied theoretically using periodic boundary conditions (PBC) at the B3LYP/6-31G(d) level. We find that the band gap of polymers is strongly dependent on the interring twist angle; yet twisting requires very little energy. A twist of 30 degrees increases the band gap by 0.75 eV in polythiophene, while requiring only 0.41 kcal mol(-1) per monomer unit. Such a small energetic value is of the order of crystal packing or van der Waals forces. These results are compared with calculations performed on model oligomers. Sexithiophene, its radical cations, and its dication are optimized at 0-180 degrees end-to-end twist angles (which correspond to 0-36 degrees interring dihedral angles) using the B3LYP/6-31G(d) method. The theoretical results suggest that the HOMO-LUMO gap, ionization potential, and charge distribution of oligomers are strongly dependent on twisting, whereas, similar to the case of polythiophene, twisting of neutral oligothiophenes costs very little energy. In the case of the radical cation, the lowest energy transition is shifted to a longer wavelength region on twisting, while the second-lowest energy transition is shifted to a shorter wavelength region. This implies that twisted, doped conducting polymers (modeled here by an oligomer radical cation), in contrast to planar, doped polymers, should be transparent within a certain optical window (in the far-visible region, at approximately 1.5 eV). This observation is explained on the basis of changes in the shape and overlap of the frontier molecular orbitals.     

QTAIM application in drug development: prediction of relative stability of drug polymorphs from experimental crystal structures

Prediction of the most stable crystal form based on the strongest intermolecular hydrogen bonds (HBs) only, was successfully applied to ten polymorphic drug systems, using the Quantum Theory of Atoms in Molecules (QTAIM). The results of the predictions were demonstrated to be superior to the thermodynamic stability ranking based on molecular mechanical (COMPASS forcefield), DFT and DFT-D calculations, as well as on the QTAIM predictions based on the total intermolecular HBing interactions strength. The obtained results support the validity of the best donor/best acceptor hierarchical approach for polymorph stability analysis of drug-like molecules: weak interactions are not as important for stability ranking as the strongest HBs. In addition, the proposed QTAIM approach allowed a reasonable ranking of the relative stability of multiple polymorphic crystalline forms of two test systems, axitinib and sulfathiazole.     

A DV-Xα study on the electronic structures of cubane-like iron-sulfur cluster compounds

The electronic structures of six cubane-like cluster compounds of the type [Fe₄S₄L₄]ⁿ (L = SH, OH, and Cl, n=-2 and ?3; L=NO, n = 0 and ?1) have been calculated by using DV-X_α method, and the bonding properties are discussed with emphasis on the ligand effect on cluster bonding. The comparisons of MO energies and cluster charge distributions with the experimental data are made, and the differences between the early studies and the present one are also briefly commented.