Substituent effects in parallel-displaced pi-pi interactions

High-quality quantum-mechanical methods are used to examine how substituents tune pi-pi interactions between monosubstituted benzene dimers in parallel-displaced geometries. The present study focuses on the effect of the substituent across entire potential energy curves. Substituent effects are examined in terms of the fundamental components of the interaction (electrostatics, exchange-repulsion, dispersion and induction) through the use of symmetry-adapted perturbation theory. Both second-order M?ller-Plesset perturbation theory (MP2) with a truncated aug-cc-pVDZ' basis and spin-component-scaled MP2 (SCS-MP2) with the aug-cc-pVTZ basis are found to mimic closely estimates of coupled-cluster with perturbative triples [CCSD(T)] in an aug-cc-pVTZ basis. Substituents can have a significant effect on the electronic structure of the pi cloud of an aromatic ring, leading to marked changes in the pi-pi interaction. Moreover, there can also be significant direct interactions between a substituent on one ring and the pi-cloud of the other ring.     

Substituent effects in pi-pi interactions: sandwich and T-shaped configurations

Sandwich and T-shaped configurations of benzene dimer, benzene-phenol, benzene-toluene, benzene-fluorobenzene, and benzene-benzonitrile are studied by coupled-cluster theory to elucidate how substituents tune pi-pi interactions. All substituted sandwich dimers bind more strongly than benzene dimer, whereas the T-shaped configurations bind more or less favorably depending on the substituent. Symmetry-adapted perturbation theory (SAPT) indicates that electrostatic, dispersion, induction, and exchange-repulsion contributions are all significant to the overall binding energies, and all but induction are important in determining relative energies. Models of pi-pi interactions based solely on electrostatics, such as the Hunter-Sanders rules, do not seem capable of explaining the energetic ordering of the dimers considered.     

Intermolecular pi-pi interactions in solids

A parameter-free DFT/CCSD(T) correction scheme is proposed for precise calculations (close to CCSD(T) accuracy) of weakly bound molecular solids. The correction scheme has been tested for solid benzene and graphite. The CCSD(T)/CBS correction to planewave DFT calculations reproduces the experimentally determined lattice constants for solid benzene. The calculated cohesive energy of benzene (457 meV per molecule) compares well with the experimental values of the heat of sublimation (460-560 meV per molecule). For graphite, the correction yields structural parameters (a = 2.46 A, c = 6.60 A) in good agreement with experiment (a = 2.46 A, c = 6.67 A). The calculated exfoliation energy of 54 meV per atom agrees fairly well with the most recent experimental value of 52 +/- 5 meV per atom.     

Functionalized [3 + 3]cycloalkynes: substituent effect on self-aggregation by nonplanar pi-pi interactions

[reaction: see text] Optically active (M)-2,11-dihydroxy-1,12-dimethylbenzo[c]phenanthrene-5,8-dicarbonitrile was synthesized from (M)-1,12-dimethyl-2,11-dinitrobenzo[c]phenanthrene-5,8-dicarbonitrile by the reduction and hydroxylation of nitro groups. The compound was converted to several oxygen-functionalized [3 + 3]cycloalkynes with -OH, -OSiMe2-t-Bu, -OAc, -OTf, or -ONf groups, which are chiral arylene ethynylene macrocycles containing three helicenes. The aggregation behaviors of these [3 + 3]cycloalkynes were examined in CHCl3, THF, and acetone using 1H NMR, CD, and vapor pressure osmometry (VPO) studies and were compared with that of the parent [3 + 3]cycloalkyne. An increasing strength of aggregation in CHCl3 was observed in the following order of the substituted derivatives: -H > -ONf > -OTf > -OAc > -OSiMe2-t-Bu. In THF the following strength of aggregation was observed: -OTf > -ONf > -OAc > -H > -OSiMe(2)-t-Bu > -OH. The aggregation of the functionalized [3 + 3]cycloalkynes is stronger for the compounds with electron-withdrawing substituents than for those with electron-donating substituents. (M)-1,12-dimethylbenzo[c]phenanthrene-2,5,8,11-tetraol was also synthesized from the same intermediate. This electron-rich helicene was readily oxidized to 5,6-quinone in air, and the quinone was suggested to form a self-charge-transfer complex in solid state.     

Local nature of substituent effects in stacking interactions

Popular explanations of substituent effects in π-stacking interactions hinge upon substituent-induced changes in the aryl π-system. This entrenched view has been used to explain substituent effects in countless stacking interactions over the past 2 decades. However, for a broad range of stacked dimers, it is shown that substituent effects are better described as arising from local, direct interactions of the substituent with the proximal vertex of the other ring. Consequently, substituent effects in stacking interactions are additive, regardless of whether the substituents are on the same or opposite rings. Substituent effects are also insensitive to the introduction of heteroatoms on distant parts of either stacked ring. This local, direct interaction viewpoint provides clear, unambiguous explanations of substituent effects for myriad stacking interactions that are in accord with robust computational data, including DFT-D and new benchmark CCSD(T) results. Many of these computational results cannot be readily explained using traditional π-polarization-based models. Analyses of stacking interactions based solely on the sign of the electrostatic potential above the face of an aromatic ring or the molecular quadrupole moment face a similar fate. The local, direct interaction model provides a simple means of analyzing substituent effects in complex aromatic systems and also offers simple explanations of the crystal packing of fluorinated benzenes and the recently published dependence of the stability of protein-RNA complexes on the regiochemistry of fluorinated base analogues [J. Am. Chem. Soc.2011, 133, 3687-3689].     

Implementation of pi-pi interactions in molecular dynamics simulation

No explicit pi-pi interaction term has been incorporated in the conventional molecular dynamics (MD) simulation programs in spite of its significant role in the folding of biomolecules and the clustering of organic chemicals. In this article, we propose a technique to emphasize the effect of pi-pi interactions using a function of energy and implement it into an MD simulation program. Several trial calculations show that the pi-pi incorporated program gives improved results consistent with experimental data on atom geometry and has no unfavorable interference with the conventional computational framework. This indicates an importance of the explicit consideration of pi-pi interactions in MD simulation.     

Unexpected halogen substituent effects on the complex thermal relaxation of naphthopyrans after UV irradiation

The kinetics of the thermal fading of four halogenated naphthopyrans (NP) have been analyzed using NMR spectroscopy in CD(3)CN. Two photomerocyanines (TT and TC) were detected after UV irradiation. The main relaxation process TC --> NP was coupled with TT/TC isomerization. The activation parameters of the various processes were rationalized by considering electronegativity and polarizability of the halogen substituents and their selective solvation by the electronegative nitrogen of acetonitrile.     

Aggregation of imine-based metallo-supramolecular architectures through pi-pi interactions

The design of supramolecular architectures based on isoquinoline-imine ligand systems is described. The isoquinoline affords an extended pi surface and the use of this surface to obtain self-recognition and consequent pi-pi aggregation is investigated. The approach is effective in that each of four complexes is observed to aggregate through these interactions. Other pi-pi interactions can interfere with the aggregation indicating that a larger pi-surface may be required to obtain complete control over the aggregation of the units.     

Tuning aryl, hydrazine radical cation electronic interactions using substituent effects

Absorption spectra for 2,3-diaryl-2,3-diazabicyclo[2.2.2]octane radical cations (2(X)(*+)) and for their monoaryl analogues 2-tert-butyl-3-aryl-2,3-diazabicyclo[2.2.2]octane radical cations (1(X)(*+)) having para chloro, bromo, iodo, cyano, phenyl, and nitro substituents are reported and compared with those for the previously reported 1- and 2(H)(*+) and 1- and 2(OMe)(*+). The calculated geometries and optical absorption spectra for 2(Cl)(*+) demonstrate that p-C6H4Cl lies between p-C6H4OMe and C6H5 in its ability to stabilize the lowest energy optical transition of the radical cation, which involves electron donation from the aryl groups toward the pi*(NN)(+)-centered singly occupied molecular orbital of 2(X)(*+). Resonance Raman spectral determination of the reorganization energy for their lowest energy transitions (lambda(v)(sym)) increase in the same order, having values of 1420, 5300, and 6000 cm(-1) for X = H, Cl, and OMe, respectively. A neighboring orbital analysis using Koopmans-based calculations of relative orbital energies indicates that the diabatic aryl pi-centered molecular orbital that interacts with the dinitrogen pi system lies closest in energy to the bonding pi(NN)-centered orbital and has an electronic coupling with it of about 9200 +/- 600 cm(-1), which does not vary regularly with electron donating power of the X substituent.     

The pi-pi stacked geometries and association thermodynamics of quinacridone derivatives studied by 1H NMR

The pi-pi stacked associations of three N,N'-di(n-butyl) quinacridone derivatives, widely used dopants in organic light-emitting diodes, with different sizes of substituents were investigated in solution at various temperatures by (1)H NMR spectroscopy. The pi-pi stacked geometries were estimated by both the magnitudes of peak shifts with concentration and the directions of peak shifts induced by polar solvents. Two patterns of geometries with different pi-pi interaction strengths were found to coexist in solution for all the three samples. In both of the patterns, the preferential orientation of the stacking is the approach of the carbonyl groups on one molecule to the nitrogen atoms on the stacked partner, which makes the pi-deficient aromatic atoms interact with both pi-rich and pi-deficient aromatic atoms of the stacked partner to maximize the electrostatic complementarity. Differently, whereas the molecules in one pattern are face-to-face stacked in a parallel fashion and slip two rings relative to one another along with the long axis of the conjugated ring systems, the molecules in the other are either face-to-face stacked in an antiparallel fashion with slight slipping between layers or stacked in a turning fashion. Both association constants obtained by fitting the dilution curves and thermodynamic parameters obtained from van't Hoff analyses revealed unexpectedly three thermodynamic processes of aggregations for all the three samples in the temperature region of 298-213 K. The size of substituents on the outer aromatic rings significantly influences the pi-pi stacked structures and association thermodynamics.     

High-accuracy quantum mechanical studies of pi-pi interactions in benzene dimers

Although supramolecular chemistry and noncovalent interactions are playing an increasingly important role in modern chemical research, a detailed understanding of prototype noncovalent interactions remains lacking. In particular, pi-pi interactions, which are ubiquitous in biological systems, are not fully understood in terms of their strength, geometrical dependence, substituent effects, or fundamental physical nature. However, state-of-the-art quantum chemical methods are beginning to provide answers to these questions. Coupled-cluster theory through perturbative triple excitations in conjunction with large basis sets and extrapolations to the complete basis set limit have provided definitive results for the binding energy of several configurations of the benzene dimer, and benchmark-quality ab initio potential curves are being used to calibrate new density functional and force-field models for pi-pi interactions. Studies of substituted benzene dimers indicate flaws in the conventional wisdom about substituent effects in pi-pi interactions. Three-body and four-body interactions in benzene clusters have also been examined.     

Hydrophobic substituent effects on proline catalysis of aldol reactions in water

Derivatives of 4-hydroxyproline with a series of hydrophobic groups in well-defined orientations have been tested as catalysts for the aldol reactions. All of the modified proline catalysts carry out the intermolecular aldol reaction in water and provide high diastereoselectivity and enantioselectivity. Modified prolines with aromatic groups syn to the carboxylic acid are better catalysts than those with small hydrophobic groups (1a is 43.5 times faster than 1f). Quantum mechanical calculations provide transition structures, TS-1a(water) and TS-1f(water), that support the hypothesis that a stabilizing hydrophobic interaction occurs with 1a.     

Interplay between cation-pi, anion-pi and pi-pi interactions.

The interplay between three important noncovalent interactions involving aromatic rings is studied by means of high level ab initio calculations. They demonstrate that very strong synergic effects are present in complexes where either cation–π or anion–π and π‐‐π interactions coexist. These strong synergic effects have been studied using the “atoms in molecules” theory and the physical nature of the interactions investigated by means of the molecular interaction potential with polarization (MIPp).     

Solid-state caging of 1,10-phenanthroline pi-pi stacked dimers by calix[4]arene dihydroxyphosphonic acid

The calix[4]arene dihydroxyphosphonic acid-1,10-phenanthroline complex shows caging of the guest molecules as a pi-pi stacked dimer in a cavity formed by intermolecular hydrogen bonds and aromatic walls formed by the calixarene.     

Ab initio study of substituent effects in the interactions of dimethyl ether with aromatic rings

Ab initio calculations have been used to investigate the interaction energies of dimers of dimethyl ether with benzene, hexafluorobenzene, and several monosubstituted benzenes. The potential energy curves were explored at the MP2/aug-cc-pVDZ level for two basic configurations of the dimers, one in which the oxygen atom of the dimethyl ether was pointed towards the aromatic ring and the other in which the oxygen atom was pointed away from the aromatic ring. Once the optimum intermolecular distances between the dimethyl and the aromatic ring had been determined for each of the dimers in both configurations at the MP2/aug-cc-pVDZ level, single point energy calculations were performed at the MP2/aug-cc-pVTZ level. A CCSD(T) correction term to the energy was determined and this was combined with the MP2/aug-cc-pVTZ energies to estimate the CCSD(T)/aug-cc-pVTZ interaction energies of the dimers. The estimated CCSD(T)/aug-cc-pVTZ interaction energies are predicted to be attractive for all of the dimers in both configurations and dispersion interactions are found to be a large component of the stabilization of the dimers. For the dimers with the dimethyl ether oxygen pointing towards the aromatic ring, the strengths of interaction energies are found to increase as the aromatic ring becomes more electron deficient, while for the dimers with the dimethyl ether oxygen pointing away from the aromatic ring, they increase as the aromatic ring becomes more electron rich. In both cases, the trends can be explained in terms of the electrostatic potentials of the dimethyl ether and the aromatic rings.     

Self-assembled monolayers of aromatic thiols stabilized by parallel-displaced pi-pi stacking interactions

Parallel-displaced pi-pi stacking interactions have been known to be the dominant force in stabilizing the double helical structure of DNA and the tertiary structure of proteins. However, little is known about their roles in self-assembled monolayers of other large pi molecules such as aromatic thiols. Here we report on a systematic study of the self-assembled monolayers of four kinds of anthracene-based thiols, 9-mercaptoanthracene (MA), (4-mercaptophenyl) (9-anthryl) acetylene (MPAA), (4-mercaptophenyl) (10-nitro-9-anthryl) acetylene (MPNAA), and (4-mercaptophenyl) (10-carboxyl-9-anthryl) acetylene (MPCAA) on Au(111), in which a spacer and different functional groups (NO2 and COOH) are intentionally designed to introduce and thus allow the investigation of various intermolecular interactions, in addition to pi-pi interactions in the base molecules. We find that all molecules form long-range-ordered monolayers and, more interestingly, that these assembled monolayers exhibit essentially the same fundamental packing structure. On the basis of high-resolution scanning tunneling microscopy observations, we propose the space-filling models for the observed superstructures and demonstrate that all superstructures can be understood in terms of the parallel-displaced pi-pi stacking interactions, despite the presence of competing dipole-dipole and H-bonding interactions associated with these specially designed functional groups.     

Anion-pi and pi-pi cooperative interactions regulating the self-assembly of nitrate-triazine-triazine complexes

We theoretically investigate the cooperative enhancement of the interactions between anions and electron-deficient aromatics by pi-pi stacking, focusing on the recent crystallographic observation of anion-pi-pi interactions in a synthesized coordination compound based on 1,3,5-triazine moieties. Using a combination of state-of-the-art dispersion-corrected density functional and quantum Monte Carlo calculations, we rationalize the unusual structural features observed in this nitrate-triazine-triazine complex. We show that the triazine rings are staggered and bent and slip with respect to each other with the nitrate bound off-center in a T-like configuration. Our results indicate that this pi-pi stacking is not simply enforced by the coordination of the triazines within the particular crystal structure but is regulated by cooperative anion-pi and pi-pi interactions. In the nitrate-triazine-triazine complex, this cooperative effect amounts to 6% of the total binding energy. Ways to further increase this energetic enhancement in the design of anion-host architectures are discussed.     

The effect of multiple substituents on sandwich and T-shaped pi-pi interactions

Sandwich and T-shaped configurations of substituted benzene dimers were studied by second-order perturbation theory to determine how substituents tune pi-pi interactions. Remarkably, multiple substituents have an additive effect on the binding energy of sandwich dimers, except in some cases when substituents are aligned on top of each other. The energetics of substituted T-shaped configurations are more complex, but nevertheless a simple model that accounts for electrostatic and dispersion interactions (and direct contacts between substituents on one ring and hydrogen atoms on the other), provides a good match to the quantum mechanical results. These results provide insight into the manner by which substituents csan be utilized in supramolecular design.     

Dibenzoeilatin: a novel ligand exhibiting remarkable complementary pi-pi stacking interactions

The complex [Ru(bpy)2(dbneil)][PF6]2 forms discrete dimers in solution held by strong pi-pi stacking interactions via its distorted dibenzoeilatin ligand, indicating that planarity is not an obligatory requirement for achieving strong pi-stacking, as long as complementarity between the stacking moieties can be achieved.