Steric Attraction Research Articles

Molecular Dynamics Simulations of Deformable Viral Capsomers.

Most coarse-grained models of individual capsomers associated with viruses employ rigid building blocks that do not exhibit shape adaptation during self-assembly. We develop a coarse-grained general model of viral capsomers that incorporates their stretching and bending energies while retaining many features of the rigid-body models, including an overall trapezoidal shape with attractive interaction sites embedded in the lateral walls to favor icosahedral capsid assembly. Molecular dynamics simulations of deformable capsomers reproduce the rich self-assembly behavior associated with a general T=1 icosahedral virus system in the absence of a genome. Transitions from non-assembled configurations to icosahedral capsids to kinetically-trapped malformed structures are observed as the steric attraction between capsomers is increased. An assembly diagram in the space of capsomer-capsomer steric attraction and capsomer deformability reveals that assembling capsomers of higher deformability into capsids requires increasingly large steric attraction between capsomers. Increasing capsomer deformability can reverse incorrect capsomer-capsomer binding, facilitating transitions from malformed structures to symmetric capsids; however, making capsomers too soft inhibits assembly and yields fluid-like structures.

Long but Strong C-C Single Bonds: Challenges for Theory.

Theoretical challenges in describing molecules with anomalously long single C-C bonds are analyzed in terms of the relative contributions of stabilizing and destabilizing intramolecular interactions. Diamondoid dimers that are stable despite the presence of C-C bonds up to 1.7 Å long, as well as other bulky molecules stabilized due to intramolecular noncovalent interactions (London dispersions) are discussed. The unexpected stability of highly crowded molecules, such as diamondoid dimers and tert-butyl-substituted hexaphenylethanes, calls for reconsideration of the "steric effect" traditionally thought to destabilize the molecule. Alternatively, "steric attraction" helps to understand bonding in sterically overloaded molecules, whose structural and energetic analysis requires a proper theoretical description of noncovalent interactions.

C-X Bond Activation by Palladium: Steric Shielding versus Steric Attraction.

The C−X bond activation (X = H, C) of a series of substituted C(n°)−H and C(n°)−C(m°) bonds with C(n°) and C(m°) = H3C− (methyl, 0°), CH3H2C− (primary, 1°), (CH3)2HC− (secondary, 2°), (CH3)3C− (tertiary, 3°) by palladium were investigated using relativistic dispersion‐corrected density functional theory at ZORA‐BLYP‐D3(BJ)/TZ2P. The effect of the stepwise introduction of substituents was pinpointed at the C−X bond on the bond activation process. The C(n°)−X bonds become substantially weaker going from C(0°)−X, to C(1°)−X, to C(2°)−X, to C(3°)−X because of the increasing steric repulsion between the C(n°)‐ and X‐group. Interestingly, this often does not lead to a lower barrier for the C(n°)−X bond activation. The C−H activation barrier, for example, decreases from C(0°)−X, to C(1°)−X, to C(2°)−X and then increases again for the very crowded C(3°)−X bond. For the more congested C−C bond, in contrast, the activation barrier always increases as the degree of substitution is increased. Our activation strain and matching energy decomposition analyses reveal that these differences in C−H and C−C bond activation can be traced back to the opposing interplay between steric repulsion across the C−X bond versus that between the catalyst and substrate.

Shape-driven, emergent behavior in active particle mixtures

Active particle systems can vary greatly from one-component systems of spheres to mixtures of particle shapes at different composition ratios. We investigate computationally the combined effect of anisotropy and stoichiometry on the collective behavior of two-dimensional active colloidal mixtures of polygons. We uncover three emergent phenomena not yet reported in active Brownian particle systems. First, we find that mixtures containing hexagons exhibit micro-phase separation with large grains of hexagonal symmetry. We quantify a measurable, implicit ‘steric attraction’ between the active particles as a result of shape anisotropy and activity. This calculation provides further evidence that implicit interactions in active systems, even without explicit attraction, can lead to an effective preferential attraction between particles. Next, we report stable fluid clusters in mixtures containing one triangle or square component. We attribute the fluidization of the dense cluster to the interplay of cluster destabilizing particles, which introduce grain boundaries and slip planes into the system, causing solid-like clusters to break up into fluid clusters. Third, we show that fluid clusters can coexist with solid clusters within a sparse gas of particles in a steady state of three coexisting phases. Our results highlight the potential for a wide variety of behavior to be accessible to active matter systems and establish a route to control active colloidal systems through simple parameter designs.

The Unique Bioorthogonal Chemistry of Isonitriles

The isocyano group is the structurally most compact bioorthogonal group known. It reacts with tetrazines under physiological conditions and has great potential for widespread use in the biosciences. In this account, we highlight the unique properties of the isocyano group as a bioorthogonal functionality. Protecting group chemistry based on the reaction of isonitriles and tetrazines that allows releasing payloads is a particular focus of the article. We further discuss the atypical steric attractions that take place in the transition state of the reaction between isonitriles and tetrazines, which result in an increase in the rate of the reaction with steric bulk of the tetrazine substituents. These findings will open up new possibilities in bioorthogonal chemistry where reactivity and stability are simultaneously desired.1 Introduction2 The Isocyano Group: A Structurally Compact Group for Bioorthogonal Chemistry3 Bioorthogonal Protecting Group Chemistry4 Steric Attractions in the Transition State Accelerate the Cycloaddition of Isonitriles and Tetrazines5 Reactions of Tetrazines and Isonitriles are Compatible with Biomolecules and Living Organisms6 Conclusions

Janus Face of the Steric Effect in a Lewis Acid Catalyst with Size-Exclusion Design: Steric Repulsion and Steric Attraction in the Catalytic Exo-Selective Diels–Alder Reaction

An exo-selective catalytic Diels–Alder reaction was developed using a Lewis acid catalyst with size-exclusion structural design. Exploiting the steric effect, especially the steric attraction, the Lewis acid catalyst was able to reroute the reaction along a higher-energy pathway. The experimental findings were also supported by theoretical calculations. This catalyst development allows an easy and practical access to highly complex and pharmaceutically relevant compounds.

Steric "attraction": not by dispersion alone.

Non-covalent interactions between neutral, sterically hindered organic molecules generally involve a strong stabilizing contribution from dispersion forces that in many systems turns the ‘steric repulsion’ into a ‘steric attraction’. In addition to London dispersion, such systems benefit from electrostatic stabilization, which arises from a short-range effect of charge penetration and gets bigger with increasing steric bulk. In the present work, we quantify this contribution for a diverse set of molecular cores, ranging from unsubstituted benzene and cyclohexane to their derivatives carrying tert-butyl, phenyl, cyclohexyl and adamantyl substituents. While the importance of electrostatic interactions in the dimers of sp2-rich (e.g., π-conjugated) cores is well appreciated, less polarizable assemblies of sp3-rich systems with multiple short-range CH···HC contacts between the bulky cyclohexyl and adamantyl moieties are also significantly influenced by electrostatics. Charge penetration is drastically larger in absolute terms for the sp2-rich cores, but still has a non-negligible effect on the sp3-rich dimers, investigated herein, both in terms of their energetics and equilibrium interaction distances. These results emphasize the importance of this electrostatic effect, which has so far been less recognized in aliphatic systems compared to London dispersion, and are therefore likely to have implications for the development of force fields and methods for crystal structure prediction.

On the structure of the P-iodo-, bromo- and chloro-bis(imino)phosphoranes: A DFT study

Abstract As demonstrated by DFT calculations, the bonding situation of P-iodo, bromo and chloro-bis(imino)phosphoranes XP(NR)2, X=Cl, Br, I, differs from that of conventional amino-bis(imino)phosphoranes (X=NR2). The monomers are highly reactive compounds with relatively small adiabatic singlet-triplet energy differences. They can dimerize by a mutual polarization mechanism between the electropositive iodine center of one monomeric unit and the more electronegative nitrogen centers of the other unit. It causes a slight depletion of p-electron density at iodine and an accumulation at the nitrogen atoms. The polarization induces electrostatic attraction, attenuated by stack formation into a one-dimensional array of monomers. The weak electrostatic binding is strongly superimposed by steric attraction among the bulky substituents of the stack array, which can end up essentially stronger than the electrostatic interaction forces. The factors which govern the dispersion forces are evaluated. The substituent effects for stack formation are studied in detail for the association of two monomers.

Role of Steric Attraction and Bite-Angle Flexibility in Metal-Mediated C–H Bond Activation

We show quantum chemically that, contrary to common believe, bulky ligands in d10-ML2 complexes may enhance, instead of counteract, L–M–L bite-angle bending. The resulting more flexible or even nonlinear geometry translates into lower barriers for oxidative addition of the methane C–H bond to these complexes. This follows from our quantum chemical analyses of the bonding in and reactivity of bisphosphine palladium complexes Pd(PR3)2 with varying steric bulk, based on relativistic dispersion-corrected DFT computations in combination with the activation strain model and quantitative MO theory. Ligands that are large but to some extent flat (instead of isotropically bulky) are shown to build up relatively strong dispersion interactions between their large surfaces (“sticky pancakes”) when they bend toward each other. The resulting stabilization, a form of steric attraction, favors bending and thus enhances bite-angle flexibility. This leads to surprisingly low reaction barriers for methane C–H activation by ...

Protein resistance of (ethylene oxide)n monolayers at the air/water interface: effects of packing density and chain length

Protein adsorption on poly(ethylene oxide) (PEO) and oligo(ethylene oxide) (OEO) monolayers is studied at different packing densities using the Langmuir technique. In the case of a PEO monolayer, a protein adsorption minimum is revealed at sigma(-1) = 10 nm(2) for both lysozyme and fibrinogen. Manifested are two packing density regimes of steric repulsion and compressive attraction between PEO and a protein on top of the overall attraction of the protein to the air/water interface. The observed protein adsorption minimum coincides with the maximum of the surface segment density at sigma(-1) = 10 nm(2). However, OEO monolayer presents a different scenario, namely that the amount of protein adsorbed decreases monotonically with increasing packing density, indicating that the OEO chains merely act as a steric barrier to protein adsorption onto the air/water interface. Besides, in the adsorption of fibrinogen, three distinct kinetic regimes controlled by diffusion, penetration and rearrangement are recognized, whereas only the latter two were made out in the adsorption of lysozyme.

Studies of Hypervalency at Phosphorus (III) by Conformational “Sonde” Method

The compounds exhibiting hypervalent interactions of nonbonded atoms may be used as models of prereaction and transition states of nucleophilic substitution reactions. Our studies of the molecules X(CH2)2-O-PCl2 (X ˭ H (1); SCN (2); C2H5 (3); CH3O (4); Cl (5) revealed the possibility of subtle intramolecular 1–5 attractions between the sulfur (2) [I] or the oxygen (4) or the chlorine (5) and the phosphorus atoms. The attractions influenced perceptibly only the energy of the conformers with intramolecular contacts between the heteroatoms. A substantial energetical preference of the convoluted conformers (B) in the liquid state was observed in the case of 2. 4 and 5. In contrast. the molecules 1 and 3 preferred to exist in liquid in extended conformations (A). These dramatic changes cannot be explained by steric reasons or Coulomb attractions, and thus were attributed to hypervalent attractions between the heteroatoms. The relative energies of (A) and (B) conformers were used in quantitative assessing of the hypervalent interactions. The energetical effect of the interactions was evaluated to be ∼2 − 4.5 kcal/mole in the liquid state.

Steric Attraction: The Far Side

The concept of steric attractions is discussed in terms of the individual contributions of repulsive and attractive terms. Examples are given in which the attractive term dominates in the equilibrium distributions of conformers, the "more crowded" confromer is lower in energy. A molecular mechanics experiment is described that emphasizes the importance of steric attractive forces in defining the steric energy of two conformations, extended vs folded, of of ethylene glycol distearate.

Conformations and conformational changes of 3-isobutyl- and 3-neopentyl-rhodanines. A case of steric attraction studied by X-ray crystallography, NOE effects and force-field calculations

An X-ray crystallographic study of 3-neopentyl-5-phenylrhodanine [3-neopentyl-5-phenyl-2-thioxo-2,3dihydro-1,3-thiazol-4(5H)-one 4] shows that the crystal is composed of the syn form, previously supposed to be less stable than the anti form. MM2(91) calculations also predict the syn form to be the most stable one due to an attractive steric effect, mainly between two methyl groups of the tert-butyl group and the nearest carbon and hydrogen atoms in the benzene ring. MM2 calculations of the barriers to rotation the 3-isobutylrhodanines 1 and 3 and on the 3-neopentyl analogues 2 and 4 reproduce the experimental barriers quite well and indicate that the preferred path of rotation of the 3-substituent is with the isopropyl or tert-butyl group passing the carbonyl rather than passing the thiocarbonyl group.A substantial NOE enhancement was observed between tert-butyl and phenyl protons, but this was not strong enough to exclude the possibility that it was caused by a minor form present in ca. 30%.

Relative stability of 1,2-difluoroethylenes

The relative energy of cis- and trans-1,2-difluoroethylene is investigated by ab initio molecular orbital theory. Hartree—Fock theory predicts the cis isomer to be most stable with the largest basis set used. Some evidence is found for steric attraction between fluorine atoms. Møl·er—Plesset theory indicates that correlation energy corrections further increase the relative stability of the cis structure.

Steric attraction

Steric attraction