Dimers of N‐Heterocyclic Carbene Copper,Silver, and Gold Halides: Probing Metallophilic Interactions through Electron Density Based Concepts

Homobimetallic metallophilic interactions between copper, silver, and gold‐based [(NHC)MX]‐type complexes (NHC=N‐heterocyclic carbene, i.e, 1,3,4‐trimethyl‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ylidene; X=F, Cl, Br, I) were investigated by means of ab initio interaction energies, Ziegler–Rauk‐type energy‐decomposition analysis, the natural orbital for chemical valence (NOCV) framework, and the noncovalent interaction (NCI) index. It was found that the dimers of these complexes predominantly adopt a head‐to‐tail arrangement with typical M ??? M distance of 3.04–3.64 Å, in good agreement with the experimental X‐ray structure determined for [{(NHC)AuCl}₂], which has an Au ??? Au distance of 3.33 Å. The interaction energies between silver‐ and gold‐based monomers are calculated to be about ?25 kcal mol^?1, whereas that for the Cu congener is significantly lower (?19.7 kcal mol^?1). With the inclusion of thermal and solvent contributions, both of which are destabilizing, by about 15 and 8 kcal mol^?1, respectively, an equilibrium process is predicted for the formation of dimer complexes. Energy‐decomposition analysis revealed a dominant electrostatic contribution to the interaction energy, besides significantly stabilizing dispersion and orbital interactions. This electrostatic contribution is rationalized by NHC(δ⁺) ??? halogen(δ^?) interactions between monomers, as demonstrated by electrostatic potentials and derived charges. The dominant NOCV orbital indicates weakening of the π backdonation in the monomers on dimer formation, whereas the second most dominant NOCV represents an electron‐density deformation according to the formation of a very weak M ??? M bond. One of the characteristic signals found in the reduced density gradient versus electron density diagram corresponds to the noncovalent interactions between the metal centers of the monomers in the NCI plots, which is the manifestation of metallophilic interaction.     

Progress in the understanding of drug-receptor interactions, part 2: experimental and theoretical electrostatic moments and interaction energies of an angiotensin II receptor antagonist (C30H30N6(O)3S)

A combined experimental and theoretical charge density study of an angiotensin II receptor antagonist (1) is presented focusing on electrostatic properties such as atomic charges, molecular electric moments up to the fourth rank and energies of the intermolecular interactions, to gain an insight into the physical nature of the drug-receptor interaction. Electrostatic properties were derived from both the experimental electron density (multipole refinement of X-ray data collected at T=17 K) and the ab initio wavefunction (single molecule and fully periodic calculations at the DFT level). The relevance of SO and SN intramolecular interactions on the activity of 1 is highlighted by using both the crystal and gas-phase geometries and their electrostatic nature is documented by means of QTAIM atomic charges. The derived electrostatic properties are consistent with a nearly spherical electron density distribution, characterised by an intermingling of electropositive and -negative zones rather than by a unique electrophilic region opposed to a nucleophilic area. This makes the first molecular moment scarcely significant and ill-determined, whereas the second moment is large, significant and highly reliable. A comparison between experimental and theoretical components of the third electric moment shows a few discrepancies, whereas the agreement for the fourth electric moment is excellent. The most favourable intermolecular bond is show to be an NHN hydrogen bond with an energy of about 50 kJ mol(-1). Key pharmacophoric features responsible for attractive electrostatic interactions include CHX hydrogen bonds. It is shown that methyl and methylene groups, known to be essential for the biological activity of the drug, provide a significant energetic contribution to the total binding energy. Dispersive interactions are important at the thiophene and at both the phenyl fragments. The experimental estimates of the electrostatic contribution to the intermolecular interaction energies of six molecular pairs, obtained by a new model proposed by Spackman, predict the correct relative electrostatic energies with no exceptions.     

Binding propensity and selectivity of cationic,anionic, and neutral guests with model hydrophobic hosts: A first principles study

Computations play a critical role in deciphering the nature of host–guest interactions both at qualitative and quantitative levels. Reliable quantum chemical computations were employed to assess the nature, binding strength, and selectivity of ionic, and neutral guests with benzenoid hosts. Optimized complex structures reveal that alkali and ammonium ions are found to be in the hydrophobic cavity, while halide ions are outside, while both complexes elicit substantial binding energy. The origin of the selectivity of host toward the guest has been traced to the interaction and deformation energies, and the nature of associated interactions is quantified using energy decomposition and the Quantum Theory of Atoms in Molecules analyses. While the larger hosts lead to loosely bound complexes, as assessed by the longer intermolecular distances, the binding strengths are proportional to the size of the host systems. The binding of cationic complexes is electrostatic or polarization driven while exchange term dominates the anionic complexes. In contrast, dispersion contribution is a key in neutral complexes and plays a pivotal role in stabilizing the polyatomic complexes.     

Structure–affinity relationships for the binding of actinomycin D to DNA

Molecular models of the complexes between actinomycin D and 14 different DNA hexamers were built based on the X-ray crystal structure of the actinomycin–d(GAAGCTTC)2 complex. The DNA sequences included the canonical GpC binding step flanked by different base pairs, nonclassical binding sites such as GpG and GpT, and sites containing 2,6-diamino- purine. A good correlation was found between the intermolecular interaction energies calculated for the refined complexes and the relative preferences of actinomycin binding to standard and modified DNA. A detailed energy decomposition into van der Waals and electrostatic components for the interactions between the DNA base pairs and either the chromophore or the peptidic part of the antibiotic was performed for each complex. The resulting energy matrix was then subjected to principal component analysis, which showed that actinomycin D discriminates among different DNA sequences by an interplay of hydrogen bonding and stacking interactions. The structure–affinity relationships for this important antitumor drug are thus rationalized and may be used to advantage in the design of novel sequence-specific DNA-binding agents.     

Electrostatics and Polarization in σ- and π-Hole Noncovalent Interactions: An Overview

The energetics of σ- and π-hole interactions can be described very well in terms of electrostatics and polarization, consistent with their Coulombic natures. When both of these components are taken into account, very good correlations with quantum-chemically computed interaction energies are obtained. If polarization is only minor, as when the interactions are quite weak, then electrostatics can suffice, as represented by the most positive electrostatic potential associated with the σ- or π-hole. For stronger interactions, the combination of electrostatics plus polarization is very effective even for interaction energies considerably greater in magnitude than what is normally considered noncovalent bonding. Several procedures for treating polarization are summarized, including the use of point charges and the direct inclusion of electric fields.     

Attraction between electrophilic caps: A counterintuitive case of noncovalent interactions

Intermolecular attractive interaction between electrophilic sites is a counterintuitive phenomenon, as the electrostatic interaction therein is repulsive and destabilizing. Here, we confirm this phenomenon in four representative complexes, using state-of-the-art quantum mechanical methods. By employing the block-localized wavefunction (BLW) method, which can turn off intermolecular charge transfer interactions, we profoundly demonstrated the significance of charge transfer interactions in these seemingly counterintuitive complexes. Indeed, after being “turned off” the intermolecular charge transfer interaction in, for example, the FNSi···BrF complex, the originally attractive intermolecular interaction turns to be repulsive. The energy decomposition approach based on the BLW method (BLW-ED) can partition the overall stability gained on the formation of intermolecular noncovalent interaction into several physically meaningful components. According to the BLW-ED analysis, the electrostatic repulsion in these counterintuitive cases is overwhelmed by the stabilizing polarization, dispersion interaction, and most importantly, the charge transfer interaction, resulting in the eventual counterintuitive overall attraction. The present study suggests that, predicting bonding sites of noncovalent interactions using only the “hole” concept may be not universally sufficient, because other significant stabilizing factors will contribute to the stability and sometimes, play even bigger roles than the electrostatic interaction and consequently govern the complex structures. © 2018 Wiley Periodicals, Inc.     

The Balance between Hydrogen Bonds,Halogen Bonds,and Chalcogen Bonds in the Crystal Structures of a Series of 1,3,4-Chalcogenadiazoles

In order to explore how specific atom-to-atom replacements change the electrostatic potentials on 1,3,4-chalcogenadiazole derivatives, and to deliberately alter the balance between intermolecular interactions, four target molecules were synthesized and characterized. DFT calculations indicated that the atom-to-atom substitution of Br with I, and S with Se enhanced the σ-hole potentials, thus increasing the structure directing ability of halogen bonds and chalcogen bonds as compared to intermolecular hydrogen bonding. The delicate balance between these intermolecular forces was further underlined by the formation of two polymorphs of 5-(4-iodophenyl)-1,3,4-thiadiazol-2-amine; Form I displayed all three interactions while Form II only showed hydrogen and chalcogen bonding. The results emphasize that the deliberate alterations of the electrostatic potential on polarizable atoms can cause specific and deliberate changes to the main synthons and subsequent assemblies in the structures of this family of compounds.     

Theoretical investigations on chalcogen-chalcogen interactions: what makes these nonbonded interactions bonding?

To understand the intermolecular interactions between chalcogen centers (O, S, Se, Te), quantum chemical calculations on pairs of model systems were carried out. For the oxygen derivatives, one of the components of the supermolecules consists of dimethyl ether, while the second component is either dimethyl ether (1) or ethynyl methyl ether (2) or methyl cyanate (3). The model calculations were also extended to the sulfur (4-6), selenium (7-9), and tellurium congeners (10-12). The MP2/SDB-cc-pVTZ, 6-311G level of theory was used to derive the geometrical parameters and the global energies of the model systems. A detailed analysis based on symmetry adapted perturbation theory (SAPT) reveals that induction and dispersion forces contribute to the bonding in each case. For 1-3 the electrostatic energy also contributes to the intermolecular bonding, but not for 4-12. The NBO analysis reveals that the interaction in the dimers 1-3 is mainly due to weak hydrogen bonding between methyl groups and chalcogen centers. Similar hydrogen bonding is also found in the case of 4 and to a lesser extent in 5 and 7. For the aggregates with heavier centers the chalcogen-chalcogen interaction dominates, and hydrogen bonding only plays a minor role. Electron-withdrawing groups on the chalcogen centers increase the interaction energy and reduce the intermolecular distance dramatically. The one-electron picture of an interaction between the lone pair of the donor and the chalcogen carbon sigma orbital allows a qualitatively correct reproduction of the observed trend.     

Structure and bonding in beta-HMX-characterization of a trans-annular N...N interaction

Chemical bonding in the beta-phase of the 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX) crystal based on the experimental electron density obtained from X-ray diffraction data at 20 K, and solid state theoretical calculations, has been analyzed in terms of the quantum theory of atoms in molecules. Features of the intra- and intermolecular bond critical points and the oxygen atom lone-pair locations are discussed. An unusual N...N bonding interaction across the 8-membered ring has been discovered and characterized. Hydrogen bonding, O...O and O...C intermolecular interactions are reported. Atomic charges and features of the electrostatic potential are discussed.     

Hydrogen Bonding between Metal‐Ion Complexes and Noncoordinated Water: Electrostatic Potentials and Interaction Energies

The hydrogen bonding of noncoordinated water molecules to each other and to water molecules that are coordinated to metal‐ion complexes has been investigated by means of a search of the Cambridge Structural Database (CSD) and through quantum chemical calculations. Tetrahedral and octahedral complexes that were both charged and neutral were studied. A general conclusion is that hydrogen bonds between noncoordinated water and coordinated water are much stronger than those between noncoordinated waters, whereas hydrogen bonds of water molecule in tetrahedral complexes are stronger than in octahedral complexes. We examined the possibility of correlating the computed interaction energies with the most positive electrostatic potentials on the interacting hydrogen atoms prior to interaction and obtained very good correlation. This study illustrates the fact that electrostatic potentials computed for ground‐state molecules, prior to interaction, can provide considerable insight into the interactions.     

Differences in structure, energy, and spectrum between neutral, protonated, and deprotonated phenol dimers: comparison of various density functionals with ab initio theory

We have carried out extensive calculations for neutral, cationic protonated, anionic deprotonated phenol dimers. The structures and energetics of this system are determined by the delicate competition between H-bonding, H-π interaction and π-π interaction. Thus, the structures, binding energies and frequencies of the dimers are studied by using a variety of functionals of density functional theory (DFT) and M?ller-Plesset second order perturbation theory (MP2) with medium and extended basis sets. The binding energies are compared with those of highly reliable coupled cluster theory with single, double, and perturbative triple excitations (CCSD(T)) at the complete basis set (CBS) limit. The neutral phenol dimer is unique in the sense that its experimental rotational constants have been measured. The geometry of the neutral phenol dimer is governed by the hydrogen bond formed by two hydroxyl groups and the H-π interaction between two aromatic rings, while the structure of the protonated/deprotonated phenol dimers is additionally governed by the electrostatic and induction effects due to the short strong hydrogen bond (SSHB) and the charges populated in the aromatic rings in the ionic systems. Our salient finding is the substantial differences in structure between neutral, protonated, and deprotonated phenol dimers. This is because the neutral dimer involves in both H(π)···O and H(π)···π interactions, the protonated dimer involves in H(π)···π interactions, and the deprotonated dimer involves in a strong H(π)···O interaction. It is important to compare the reliability of diverse computational approaches employed in quantum chemistry on the basis of the calculational results of this system. MP2 calculations using a small cc-pVDZ basis set give reasonable structures, but those using extended basis sets predict wrong π-stacked structures due to the overestimation of the dispersion energies of the π-π interactions. A few new DFT functionals with the empirical dispersion give reliable results consistent with the CCSD(T)/CBS results. The binding energies of the neutral, cationic protonated, and anionic deprotonated phenol dimers are estimated to be more than 28.5, 118.2, and 118.3 kJ mol(-1), respectively. The energy components of the intermolecular interactions for the neutral, protonated and deprotonated dimers are analyzed.     

Pancake Bonding: An Unusual Pi-Stacking Interaction

A category of parallel π-stacking interaction, termed pancake bonding, is surveyed. The main characteristics are: the interaction occurs among radicals with highly delocalized π-electrons in their singly occupied molecular orbitals (SOMOs), the contact distances in the π-stacking direction are shorter than the typical van der Waals distances, and the stabilization obtained by the bonding combination of the SOMO orbitals leads to direct atom-to-atom overlap with strong orientational preferences. These atypical intermolecular interactions contain a component of electron sharing between the radicals that can be viewed as covalent-like. Pancake bonded dimers characteristically have low-lying singlet and triplet states and show characteristic interlayer vibrational modes. Pancake bonded aggregates serve as molecular components in many conducting and other functional organic materials. The role of van der Waals (vdW) interactions in pancake bonded dimers, chains, and other aggregates is different from closed shell vdW aggregates: here the Pauli repulsions reduce the attractive dispersion interaction significantly. Fluxionality between π- and σ-bonded aggregates often occur in the context of pancake bonding. Both experimental and computational aspects are reviewed.     

Critical examination of the supermolecule density functional theory calculations of intermolecular interactions

The results of calculations employing twelve different combinations of exchange and correlation functionals are compared with results of ab initio calculations for two different configurations of the water dimer and three different configurations of the thymine-adenine complex. None of the density functional theory (DFT) treatments could properly reproduce the results of coupled-cluster calculations for all configurations examined. The DFT approaches perform well when the interaction energy is dominated by the electrostatic component and the dispersion energy is less important. Two mechanisms that compensate for the missing dispersion component were identified. The first one is the decrease of the magnitude of the intermolecular exchange-repulsion and the second one is the increase of the magnitude of the attractive deformation energy. For some functionals both effects are observed together, but for some other ones only the second effect occurs. The three correlation functionals that were examined were found to make only very small contributions to the deformation energy. The examination of angular and distance dependence of the interactions shows that the currently available DFT approaches are not suitable for developing intermolecular potential energy surfaces. They could however be used to find global minima on potential energy surfaces governed by intermolecular electrostatic interactions. Additional single point ab initio calculations are recommended as the means of validating optimized structures.     

Amphiphilic organic ion pairs in solution: a theoretical study.

The macroscopic manifestation of hydrophobic interactions for amphiphilic organic ion pairs (tetraalkylammonium-anion) has been shown experimentally by measuring their association constants and their affinity with the organic phase. Beyond a certain size, there is a direct relation between association constants and chain lengths in tetraalkylammonium ions. We propose to cast a bridge between these results and geometrical properties considered at the level of a single ion pair by means of quantum chemistry calculations performed on model systems: trimethylalkylammonium-pentyl sulfate instead of tetraalkylammonium-dodecyl sulfate. Two limiting cases are considered: head-to-head configurations, which yield an optimal electrostatic interaction between polar heads, and parallel configurations with a balance between electrostatic and hydrophobic interactions. All properties (geometries, complexation energies, and atomic charges) were obtained at the MP2 level of calculation, with water described by a continuum model (CPCM). Dispersion forces link hydrocarbon chains of tetraalkylammonium ions and pentyl sulfate, thus yielding (for the largest ion pairs) parallel configurations favored with respect to head-to-head geometries by solute-solvent electrostatic interactions. Given the small experimental association energies, we probe the accuracy limit of the MP2 and CPCM methods. However, clear trends are obtained as a function of chain length, which agree with the experimental observations. The calculated monotonic stabilization of ion pairs when the hydrocarbon chain increases in length is discussed in terms of electrostatic interactions (between ions and between ion pairs and water), dispersion forces, and cavitation energies.     

Polyelectrolyte-mediated bridging interactions

Polyelectrolyte chains confined by macroions bearing electrostatic charges of opposite sign can mediate an effective attraction between the macroions. This polyelectrolyte-mediated attraction is usually referred to as the bridging interaction. I review the theories of polyelectrolyte-mediated interactions based on analytic mean-field and variational approaches. I will describe the origin and the salient properties of this interaction in the context of planar and point macroions with special emphasis on the connection between the polymer chain conformations and the ensuing polymer mediated interactions. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3539–3556, 2004     

Molecular dynamics simulations of polyelectrolyte-polyampholyte complexes. Effect of solvent quality and salt concentration

Complexation between polyelectrolyte and polyampholyte chains in poor solvent conditions for the polyelectrolyte backbone has been studied by molecular dynamics simulations. In a poor solvent a polyelectrolyte forms a necklace-like structure consisting of polymeric globules (beads) connected by strings of monomers. The simulation results can be explained by assuming the existence of two different mechanisms leading to the necklace formation. In the case of weak electrostatic interactions, the necklace formation is driven by optimization of short-range monomer-monomer attraction and electrostatic repulsion between charged monomers on the polymer backbone. In the case of strong electrostatic interactions, the necklace structure appears as a result of counterion condensation. While the short-range attractions between monomers are still important, the correlation-induced attraction between condensed counterions and charged monomers and electrostatic repulsion between uncompensated charges provide significant contribution to optimization of the necklace structure. Upon forming a complex with both random and diblock polyampholytes, a polyelectrolyte chain changes its necklace conformation by forming one huge bead. The collapse of the polyelectrolyte chain occurs due to the neutralization of the polyelectrolyte charge by polyampholytes. In the case of the random polyampholyte, the more positively charged sections of the chain mix with negatively charged polyelectrolyte forming the globular bead while more negatively charged chain sections form loops surrounding the collapsed core of the aggregate. In the case of diblock polyampholyte, the positively charged block, a part of the negatively charged block, and a polyelectrolyte chain form a core of the aggregate with a substantial section of the negatively charged block sticking out from the collapsed core of the aggregate. In both cases the core of the aggregate has a layered structure that is characterized by the variations in the excess of concentration of monomers belonging to polyampholyte and polyelectrolyte chains throughout the core radius. These structures appear as a result of optimization of the net electrostatic energy of the complex and short-range attractive interactions between monomers of the polyelectrolyte chain.     

A generalized formulation of ion-π electron interactions: role of the nonelectrostatic component and probe of the potential parameter transferability

The intermolecular potentials for hexafluorobenzene (HFBz) and 1,3,5-trifluorobenzene (TFBz) interacting with alkali (M(+); M = Li, Na, K, Rb, Cs) and halogen (X(-); X = F, Cl, Br, I) ions are provided as a combination of electrostatic and nonelectrostatic terms. The ion-HFBz and ion-TFBz electrostatic components are formulated as a sum of Coulombic potentials associated with the interactions between the ion charge and point charges on the molecular frame, whose distributions are consistent with the permanent quadrupole moment of HFBz and TFBz, respectively. The corresponding nonelectrostatic components are represented as a sum of effective potential functions, each one having a specific physical meaning, related to ion-molecular bond pair interactions. In the present paper, we test the transferability of the ion-bond potential parameters. Moreover, the powerfulness of the model is analyzed by comparing predicted binding energies and equilibrium geometries for the family of M(+)-HFBz, X(-)-HFBz, M(+)-TFBz, and X(-)-TFBz systems with available ab initio results.     

The Effect of Deoxyfluorination on Intermolecular Interactions in the Crystal Structures of 1,6-Anhydro-2,3-epimino-hexopyranoses

The effect of substitution on intermolecular interactions was investigated in a series of 1,6-anhydro-2,3-epimino-hexopyranoses. The study focused on the qualitative evaluation of intermolecular interactions using DFT calculations and the comparison of molecular arrangements in the crystal lattice. Altogether, ten crystal structures were compared, including two structures of C4-deoxygenated, four C4-deoxyfluorinated and four parent epimino pyranoses. It was found that the substitution of the original hydroxy group by hydrogen or fluorine leads to a weakening of the intermolecular interaction by approximately 4 kcal/mol. The strength of the intermolecular interactions was found to be in the following descending order: hydrogen bonding of hydroxy groups, hydrogen bonding of the amino group, interactions with fluorine and weak electrostatic interactions. The intermolecular interactions that involved fluorine atom were rather weak; however, they were often supported by other weak interactions. The fluorine atom was not able to substitute the role of the hydroxy group in molecular packing and the fluorine atoms interacted only weakly with the hydrogen atoms located at electropositive regions of the carbohydrate molecules. However, the fluorine interaction was not restricted to a single molecule but was spread over at least three other molecules. This feature is a base for similar molecule arrangements in the structures of related compounds, as we found for the C4-F_ax and C4-F_eq epimines presented here.