Flexibility and lengths of bis-peptide nanostructures by electron spin resonance

We demonstrate the use of electron spin resonance (ESR) to determine long-range distances and flexibility in water-soluble bis-peptide molecular rods. Bis-peptide oligomers with 4-8 monomer units were synthesized. ESR determined that the end-to-end length of the peptides is linearly proportional to the number of monomers. The linear shape is, therefore, easily interpreted from the data. In addition, the flexibility of the rods was quantified directly from the ESR-determined distance distribution functions. Quantitative information on chain length and flexibility is important to develop the use of these oligomers as rodlike structural elements for applications such as bivalent display of ligands and as elements of future nanoscale devices.     

Spiroligomer-Based Macrocycles for Atomically Precise Membranes

Here, we report a new class of peptidomimetic macrocycles with well-defined three-dimensional structures and low conformational flexibility. They are assembled from fused-ring spiro-ladder oligomers (spiroligomers) by modular solid-phase synthesis. Two-dimensional nuclear magnetic resonance confirms their shape persistency. Triangular macrocycles of tunable sizes assemble into membranes with atomically precise pores, which exhibit size and shape-dependent molecular sieving towards a series of structurally similar compounds. The exceptional structural diversity and stability of spiroligomer-based macrocycles will be explored for more applications.     

Optical, redox, and NLO properties of tricyanovinyl oligothiophenes: comparisons between symmetric and asymmetric substitution patterns

A series of tricyanovinyl (TCV)-substituted oligothiophenes was synthesized and investigated with a number of physical methods including UV/Vis, IR, and Raman spectroscopy, nonlinear optical (NLO) measurements, X-ray diffraction, and cyclic voltammetry. Mono- or disubstituted oligomers were prepared by the reaction of tetracyanoethylene with mono- or dilithiated oligomers. The comparative effects of the symmetric and asymmetric substitutions in the electronic and molecular properties have been addressed. These oligomers display dramatic reductions in both their optical and electrochemical band gaps in comparison with unsubstituted molecules. The analysis of the electronic properties of the molecules was assisted by density functional theory calculations, which are in excellent agreement with the experimental data. TCV substitution influences the energies of the frontier orbitals, especially with respect to the stabilization of LUMO orbitals. X-ray structural characterization of a monosubstituted oligomer exhibits pi-stacking with favorable intermolecular interactions. NLO results agree with the role of the intramolecular charge-transfer feature in the asymmetric samples. These results furthermore exalt the role of conformational flexibility in the disubstituted compounds and reveal an unexpected nonlinear optical activity for symmetric molecules. Regarding the electronic structure, the interpretation of the vibrational data reflects the balanced interplay between aromatic and quinoid forms, finely tuned by the chain length and substitution pattern. The electronic and structural properties are consistent with the semiconducting properties exhibited by these materials in thin film transistors (TFTs).     

Spectroscopy and photophysics of methylphenylsiloxaneand diphenylsiloxane-based molecules and polymers

Spectroscopy and photophysics of various types of methylphenylsiloxane- and diphenylsiloxane-based oligomers and polymers are reviewed. The molecules treated here include homopolymers such as poly(methylphenylsiloxane) and copolymers such as poly(dimethylsiloxane-codiphenylsiloxane) as well as related oligomers or molecules such as diphenyltetramethyldisiloxane. These polymers and oligomers normally exhibit monomer fluorescence in fluid solution at temperatures near room temperature, and the monomer fluorescence and phosphorescence in rigid matrices at 77 K. In addition to these emissions, the excimer fluorescence is often observed depending on the molecular structure of the siloxanes. These emission properties are rationalized based on the molecular structure and kinetics of the excimer formation processes as well as on the flexibility of the Si-O-Si bonds.     

Distinctive dielectric properties of nematic liquid crystal dimers

ABSTRACT

We provide an overview of the effect of the molecular structure on the dielectric properties of dimers exhibiting nematic and twist-bend nematic phases with special focus on how the conformational distribution changes are reflected by the dielectric behaviour. Nematic dimers show distinctive dielectric properties which differ from those of archetypical nematic liquid crystals, as for example, unusual temperature dependence of the static permittivity or dielectric spectra characterised by two low-frequency relaxation processes with correlated strengths. The interpretation of such characteristic behaviour requires that account is taken of the effect of molecular flexibility on the energetically favoured molecular shapes. The anisotropic nematic interactions greatly influence the conformational distribution. Dielectric behaviour can be used to track those conformational changes due to dependence of the averaged molecular dipole moment on the averaged molecular shape. Results for a number of dimers are compared and analysed on the basis of the influence of details of the molecular structure, using a recently developed theory for the dielectric properties of dimers.     

Molecular similarity studies on sandalwood odour molecules: Investigations of the conformational space

Summary Odour differences of some campholene and fencholene derivatives are explained by the analysis of the conformational space and the molecular shape of these molecules. The high flexibility caused by free rotation of some carbon-carbon bonds leads in one case to a large number of energetically possible conformations which have to be taken into account for a study of molecular similarity. In another case, steric restrictions reduce the number of relevant conformations such that no active conformation exists in a thermodynamic equilibrium.Conformational Calculations on Sandalwood Odour XII; for part XI, see Ref. [1]     

ELECT++: Faster conformational search method for docking flexible molecules using molecular similarity

We have developed a program, ELECT++ (Effective LEssening of Conformations by Template molecules in C++), to speed up the conformational search for small flexible molecules using the similar property principle. We apply this principle to molecular shape and, importantly, to molecular flexibility. After molecules in a database are clustered according to flexibility and shape (FCLUST++), additional reagents are generated to screen the conformational space of molecules in each cluster (TEMPLATE++). We call these representative reagents of each cluster template reagents. Template reagents and clustered reagents produce, after reaction, template molecules and clustered molecules, respectively (tREACT++). The conformations of a template molecule are searched in the context of a macromolecular target. Acceptable conformational choices are then applied to all molecules in its cluster, thus effectively biasing conformational space to speed up conformational searches (tSEARCH++). In our incremental search method, it is necessary to calculate the root-mean-square deviations (RMSD) matrix of distances between different conformations of the same molecule to reduce the number of conformations. Instead of calculating the RMSD matrix for all molecules in a cluster, the RMSD matrix of a template molecule is chosen as a reference and applied to all the molecules in its cluster. We demonstrate that FCLUST++ clusters the primary amine reagents from the Available Chemicals Directory (ACD) successfully. The program tSEARCH++ was applied to dihydrofolate reductase with virtual molecules generated by tREACT++ using clustered primary amine reagents. The conformational search by the program tSEARCH++ was about 4.8 times faster than by SEARCH++, with an acceptable range of errors. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1834–1852, 1998     

Synthesis of molecular objects: Two-dimensional polymers

Throughout this century polymer science has studied the linear chain and its architectural derivatives which include familiar forms such as the branched chain and the three dimensional network. Other derivatives with unique properties have been investigated more recently and include macromolecular rings, dendrimers, stars, combs and ladders. The objective of this work is to depart from the focus on linear chains and explore the “bulk” synthesis and properties of polymer molecules that can be considered molecular objects. Ideal molecular objects should be macromolecules with well defined shapes that persist as systems transform reversibly from solids to melts or solutions. The limited access to conformational space which is required in order to define and maintain shape in liquid and solid states of the system is an unusual molecular characteristic in common polymers. Our ability to create such objects through bulk reactions of reasonable scale will undoubtedly extend the current boundaries of polymer science and technology. Shapes that are particularly interesting are those not common in the conformational space of linear chains, for example, two-dimensional polymers shaped as plates and macromolecular bundles shaped as cylinders or parallelepipeds. The molecular object to be discussed in this lecture is a rigid and anisotropic two-dimensional polymer with planar dimensions greater than its thickness and a shape-granting skeleton built by covalent bonds. We have so far developed three different strategies for their synthesis, all involving systems in which reactive oligomers organize spontaneously into the necessary planar assemblies to form the object. In one strategy molecular recognition driven by homochiral interactions plays a key role in the formation of two-dimensional polymers.¹ A different methodology relies on entropy-driven nanophase separation in rodcoil block molecules in which a rigid segment is covalently bonded to a flexible one sharing the same backbone. The third strategy involves the folding of oligomers into hairpin structures which self assemble into two-dimensional liquids. The lecture will also describe examples of unique properties that could be achieved in materials containing these rigid two-dimensional objects. These examples will include bulk materials with self-organized surfaces and also remarkably stable nonlinear optical properties.     

Ionic peptide aggregation: exploration of conformational dynamics in aqueous solution by computational techniques

The effects of end groups on KEK peptide conformational characteristics and self-assembling properties in water solution are investigated by using long lasting all-atom molecular dynamics simulations. The analysis of the structural macroscopic and microscopic properties and the examination of intra- and intermolecular interactions suggest, in agreement with experimental observations, the role played by side chains and terminal regions in determining the characteristic features of the assemblages. Competition between intra- and interchain interactions greatly affects the diffusivity of peptide molecules and the conformational space that they can sample, ultimately controlling the shape, size, and distribution of the aggregate configurations. Different peptide end groups influence peptide flexibility and seem to play a crucial role in determining the aggregates' supramolecular architectures.     

Cages, baskets, ladders, and tubes: conformational studies of polyhedral oligomeric silsesquioxanes

The conformational flexibility of a series of cage, basket, ladder, and tube polyhedral oligomeric silsesquioxanes (POSS) has been examined using the Low Mode:Monte Carlo conformational search method in conjunction with the MM3/GBSA(CHCl3) surface. An ensemble of low energy structures was generated and used to explore the molecular shape and flexibility of each system. The results indicate that, except for the ladder molecule, the incompletely condensed systems that are studied are relatively rigid. Even in cases where the molecule is able to adopt numerous low energy conformations, the overall shape remains cage-like and the conformations differ only by small angles or substituent orientations. The ladder molecule is the most flexible and this ensemble clusters into two families: one that is cage-like and the other that is more open and ladder-like. The conformational flexibilities in the gas and solvent phases, as approximated using the GBSA continuum solvent model, are very similar.     

Minimizing the Entropy Penalty for Ligand Binding: Lessons from the Molecular Recognition of the Histo Blood‐Group Antigens by Human Galectin‐3

Ligand conformational entropy plays an important role in carbohydrate recognition events. Glycans are characterized by intrinsic flexibility around the glycosidic linkages, thus in most cases, loss of conformational entropy of the sugar upon complex formation strongly affects the entropy of the binding process. By employing a multidisciplinary approach combining structural, conformational, binding energy, and kinetic information, we investigated the role of conformational entropy in the recognition of the histo blood‐group antigens A and B by human galectin‐3, a lectin of biomedical interest. We show that these rigid natural antigens are pre‐organized ligands for hGal‐3, and that restriction of the conformational flexibility by the branched fucose (Fuc) residue modulates the thermodynamics and kinetics of the binding process. These results highlight the importance of glycan flexibility and provide inspiration for the design of high‐affinity ligands as antagonists for lectins.     

Elution Behaviors and Rationalized Calibration for Low-Molecular-Weight Polymers in Size Exclusion Chromatography

Abstract

Molecular weight relationships among oligostyrene, n-hydrocarbon, epoxy resin, p-cresol novolak resin, and oligoethylene glycol having the same retention volume were discussed using SEC gels of different pore sizes in chloroform and tetrahydrofuran. Gel capacity and the maximum number of components resolvable increased with the use of chloroform except the case of epoxy resin. Different elution behaviors of oligomers in different eluents make it difficult to use molar volumes or effective chain lengths as calibration parameters. The influence of the pore size and shape of the gel on the elution order among oligomers was negligible except some cases. Molecular weight conversion equations for several oligomers based on molecular weight of oligostyrene or n-hydrocarbon were derived. These equations make it possible to use oligostyrene or n-hydrocarbon as a reference standard when molecular weights of oligomers are measured.     

Direct Observation of Kinetic Pathways of Biomolecular Recognition

The pathways of molecular recognition, which is a central event in all biological processes, belong to the most important subjects of contemporary research in biomolecular science. By using fluorescence spectroscopy in a microfluidics channel, it can be determined that molecular recognition of α‐chymotrypsin in hydrous surroundings at two different pH values (3.6 and 6.3) follows two distinctly different pathways. Whereas one corroborates an induced‐fit model (pH 3.6), the other one (pH 6.3) is consistent with the selected‐fit model of biomolecular recognition. The role of massive structural perturbations of differential recognition pathways could be ruled out by earlier XRD studies, rather was consistent with the femtosecond‐resolved observation of dynamic flexibility of the protein at different pH values. At low concentrations of ligands, the selected‐fit model dominates, whereas increasing the ligand concentration leads to the induced‐fit model. From molecular modelling and experimental results, the timescale associated with the conformational flexibility of the protein plays a key role in the selection of a pathway in biomolecular recognition.     

(Thermo)dynamic Role of Receptor Flexibility,Entropy, and Motional Correlation in Protein–Ligand Binding

The binding of 2‐amino‐5‐methylthiazole to the W191G cavity mutant of cytochrome c peroxidase is an ideal test case to investigate the entropic contribution to the binding free energy due to changes in receptor flexibility. The dynamic and thermodynamic role of receptor flexibility are studied by 50 ns‐long explicit‐solvent molecular dynamics simulations of three separate receptor ensembles: W191G binding a K⁺ ion, W191G–2a5mt complex with a closed 190–195 gating loop, and apo with an open loop. We employ a method recently proposed to estimate accurate absolute single‐molecule configurational entropies and their differences for systems undergoing conformational transitions. We find that receptor flexibility plays a generally underestimated role in protein–ligand binding (thermo)dynamics and that changes of receptor motional correlation determine such large entropy contributions.     

Structural features of fullerene-containing star-shaped polystyrene molecules with Oligomer arms in solutions

The structure and conformational properties of star-shaped oligostyrenes containing fullerene C₆₀ as a branching center and short arms with lengths at the level of the persistent length or a segment of a polystyrene chain are studied by small-angle neutron scattering in deuterotoluene. The gyration radii of linear precursor oligomers (～0.4 and 0.6 nm) and corresponding star-shaped molecules (～1.1 and 1.4 nm) are calculated under the Guinier approximation. The linear oligomer (4–5 units) is found to be a rodlike molecule; arms of star-shaped molecules based on it assume the straightened conformations as well. Linear oligomer chains composed of 6–7 units deviate from the rodlike shape and acquire a certain flexibility in solution, but oligomer chains grafted onto the C₆₀ center preserve the extended conformations. There is no marked tendency toward screening of fullerene by radially extended arms. The number of branches in the star-shaped oligostyrenes corresponds to a functionality of f = 6 preset by the conditions of synthesis.     

Optical and electro-optical properties of silicon-contaning thiophene derivatives of star-shaped and dendritic structure

Star-thiophene derivatives with a silicon atom as the branching center were investigated by absorption spectroscopy and electro-optical Kerr effect in solutions at variations in a number and chemical structure of branches. The star-shaped oligomers were compared with dendritic analogues containing silicon atoms at the points of branching. It is shown that thiophene-containing moieties determine both spectral and electrooptical properties of the molecules. Molecular parameters of the star-shaped oligomers of various structure vary identically with increasing the number of branches. The absorption of star-shaped oligomers is additive due to the autonomy of the absorption of radiation by the separate branches. For dendritic molecules the additive nature of the absorption is kept, but their electro-optical properties are independent of a generation number. It was shown that the latter is a consequence of the manifestation by dendrimers of deformation flexibility, which is not peculiar to the starshaped derivatives.     

Alkylenesulfanyl-bridged bithienyl cores for simultaneous tuning of electronic, filming, and thermal properties of oligothiophenes

DPY and DPE alkylenesulfanyl-bridged bithienyls were prepared by a highly effective ring-closing reaction via arylalkylsulfonium intermediate and used as inner cores in oligothiophenes. HOMO-LUMO energy levels, conformational flexibility, and intrinsic asymmetry of the cores are reflected in the electronic, film-forming, and thermal properties of the corresponding oligomers.     

Molecular dynamics and X-ray scattering simulations of cyclic siloxane-based liquid crystal mesogens

Molecular dynamics simulations of cyclic siloxane-based liquid crystals offer new insights into the conformational flexibility of these materials. Interdigitation between the cholesteryl-4'-allyloxybenzoate and biphenyl-4'-allyloxybenzoate mesogens pendant on the cyclic siloxane ring is observed in the simulated structures. All molecular models considered viz. disc, cone, and cylinder, display a large conformational flexibility, which is important regarding the liquid crystalline phase behavior. The disc molecular model exhibits the largest flexibility as indicated by mean dihedral angles and their range for certain principal torsions, evaluated from the molecular dynamics simulations. Results from the dynamics simulations of cylinder molecular pairs indicate a significant amount of conformational flexibility in the siloxane rings. The degree of interdigitation between mesogens is dependent on the flexibility of the siloxane rings, as shown by calculations for a fixed ring system resulting in less interdigitation, also reflected in calculated X-ray scattering sections along the starting molecular direction. Weaker molecular transforms were observed for the non-fixed system due to a lack of boundary conditions. In general, the qualitative agreement of the starting structure's reflections and those shown by the experimental data is encouraging.     

Nitroxyls and PELDOR: Nitroxyl radicals in pulsed electron-electron double resonance spectroscopy

The review considers the main propositions of PELDOR theory. It is shown how from the analysis of PELDOR time traces it is possible to find the parameters of a spin system such as the distance and the distance distribution (spectrum), number of spins in aggregates and complexes, exchange integral and how to separate for the following analysis the inter- and intramolecular contributions to the general dipole interaction. Examples of PELDOR application in the studies of the spatial distribution of nitroxyl radicals, the charge effect of dipolar interacting nitroxyls on their spatial distribution are given and the results of the determination of distances and the spectrum of distances for nitroxyl bi-, tri-, and tetraradicals are presented. The works on nitroxyl radicals in which the orientation selectivity effect, spin exchange, and conformational properties of the radicals are examined by the PELDOR method are analyzed. The studies of the structure of paramagnetic ion-nitroxyl radical pairs and the PELDOR data on nitroxyls at high frequencies (high fields) are considered. The last section of the review is devoted to the works examining the properties such as the molecular flexibility of oligomers and supramolecules contains nitroxyl radicals.     

Structural biology of the cell adhesion protein CD2: alternatively folded states and structure-function relation

Cluster of differentiation 2 (CD2) is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells and plays an important role in mediating cell adhesion in both T-lymphocytes and in signal transduction. The understanding of the biochemical basis of molecular recognition by the cell adhesion molecule CD2 has been advanced greatly through the determination of structures and the dynamic properties of the complexes and their individual components and through site-directed mutagenesis. A number of general principles can be derived from the structural and functional studies of the extracellular domains of CD2 and CD58 and their complex. Significant electrostatic interactions within the protein-protein interfaces contribute directly to the formation of macromolecular complexes of CD2 and CD58. Also, residues located on the protein-protein interface demonstrate a certain degree of conformational change upon the formation of a complex. Structural analysis of CD2 has revealed that this adhesion molecule exhibits strong conformational flexibility with a partial non-native helical conformation at high temperatures and in the presence of an organic solvent. In addition, it can be converted into a domain swapped dimer, or trimer and tetramer through hinge deletion. Thus, the conformational status of the adhesive proteins contributes to the regulation of cell adhesion and the folding of CD2.