Reversible formation of DNA G-quadruplex hairpin dimers from stilbenediether conjugates

Rapid and reversible G-quadruplex hairpin dimer formation is observed for bis(oligonucleotide) conjugates possessing stilbenediether (Sd) linkers connecting two short poly(G) sequences.     

A hybrid consisting of coordination polymer and noncovalent organic networks: a highly ordered 2-D phenol network assembled by edge-to-face pi-pi interactions

A 2-D metal-organic open framework having 1-D channels, [Cu(C(10)H(26)N(6))](3)[C(6)H(3)(COO)(3)](2).18H(2)O (1), was constructed by the self-assembly of the Cu(II) complex of hexaazamacrocycle A (A = C(10)H(26)N(6)) with sodium 1,3,5-benzenetricarboxylate (BTC(3)(-)) in DMSO-H(2)O solution. 1 crystallizes in the trigonal space group P with a = b = 17.705(1) A, c = 6.940(1) A, alpha = beta = 90 degrees, gamma = 120 degrees, V = 1884.0(3) A(3), Z = 1, and rho(calcd) = 1.428 g cm(-3). The X-ray crystal structure of 1 indicates that each Cu(II) macrocyclic unit binds two BTC(3-) ions in a trans position and each BTC(3-) ion coordinates three Cu(II) macrocyclic complexes to form 2-D coordination polymer layers with honeycomb cavities (effective size 8.1 A), and the layers are packed to generate 1-D channels perpendicularly to the 2-D layers. Solid 1 binds guest molecules such as MeOH, EtOH, and PhOH with different binding constant and capacity. By the treatment of 1 with aqueous solution of phenol, a hybrid solid [Cu(C(10)H(26)N(6))](3)[C(6)H(3)(COO)(3)](2).9PhOH.6H(2)O (2) was assembled. 2 crystallizes in the trigonal R3 space group with a = b = 20.461(1) A, c = 24.159(1) A, alpha = beta = 90 degrees, gamma = 120 degrees, V = 8759.2(7) A(3), Z = 3, and rho(calcd) = 1.280 g cm(-3). In 2, highly ordered 2-D noncovalent phenol layers are formed by the edge-to-face pi-pi interactions between the phenol molecules and are alternately packed with the coordination polymer layers in the crystal lattice.     

Interplay between edge-to-face aromatic and hydrogen-bonding interactions

The interplay between two important noncovalent interactions involving aromatic rings is studied by means of MP2/6-31++G** ab initio calculations. They indicate that synergistic effects are present in complexes where edge-to-face aromatic interactions and hydrogen-bonding interactions coexist. These synergistic effects have been studied bu using the atoms in molecules theory and the molecular interaction potential with polarization partition scheme. Experimental evidence for such interactions has been obtained from the Cambridge Structural Database.     

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.     

Stereodynamics and edge-to-face CH-pi aromatic interactions in o-phenethyl-substituted biaryls

As part of a search for systems that exhibit intramolecular aromatic edge-to-face interactions, a series of four biaryl compounds containing a phenethyl side chain were prepared. These compounds exist as a slowly interconverting mixture of two atropisomers due to steric hindrance to rotation about the biaryl bond. The more thermodynamically stable isomer exhibits an abnormal shielding of an ortho-proton in solution indicative of an edge-to-face CH-pi interaction with the terminal phenyl ring on the side chain. This tilted-T type of geometry was observed in the X-ray crystal structure of one of the compounds. The edge-to-face conformation in solution is estimated by variable temperature NMR studies to be energetically favored by ca. 1.6 kcal mol(-1) but entropically disfavored by ca. 5.0 cal K(-1) mol(-1).     

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.     

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 substituent effects in offset pi-pi stacked interactions in water

We have measured the rotational barriers of meta- and para-substituted N-benzyl-2-(2-fluorophenyl)pyridinium bromides in aqueous solution by dynamic NMR as a model system for offset-stacking interactions in proteins. Because the benzyl ring can stack with the 2-fluorophenyl ring in the offset conformation in the ground state, but not the transition state, the rotational barrier reflects the magnitude of the stacking interaction. Only a small (0.1 kcal/mol) change in rotational barrier was found for para substituents relative to hydrogen. A much larger energy difference was found for electronegative meta substituents (up to 0.66 kcal/mol for CF3). Evidence suggests that this is due at least in part to an electrostatic interaction between electron-poor hydrogens on one ring with the electronegative substituents on 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.     

An electrochemically controllable nanomechanical molecular system utilizing edge-to-face and face-to-face aromatic interactions

[formula: see text] A new molecular system, 2,11-dithio[4,4]metametaquinocyclophane containing a quinone moiety, was designed and synthesized. As the quinone moiety can readily be converted into an aromatic pi-system (hydroquinone) upon reduction, the nanomechanical molecular cyclophane system exhibits a large flapping motion like a molecular flipper from the electrochemical redox process. The conformational changes upon reduction and oxidation are caused by changes of nonbonding interaction forces (devoid of bond formation/breaking) from the edge-to-face to face-to-face aromatic interactions and vice versa, respectively.     

Luminescent 1D chain of platinum(II) terpyridyl units with p-dithiobenzoquinone organometallic linker: self-aggregation imparted from Pt...Pt/pi-pi interactions

Unlike p-dithiobenzoquinone (), which is extremely reactive and has never been isolated, the metal-stabilised p-dithiobenzoquinone [Cp*Ir(eta4-C6H4S2)] () was prepared and used as an efficient organometallic linker to construct novel supramolecular assemblies. Treatment of with the electrophilic Pt(II)(terpy) building blocks produced the supramolecular assembly {[Pt(terpy){Cp*Ir-p-(eta4-C6H4S2)}Pt(terpy)][OTf]4}n (), which was fully characterised and its molecular structure was determined by X-ray crystallography. The structure of revealed the presence of pi-pi and Pt[dot dot dot]Pt interactions among individual molecules describing a 1D chain. Complex showed unusual UV/Vis absorption and luminescence behaviour at low temperature, imparted from self-aggregation mediated by pi-pi and Pt...Pt interactions.     

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).     

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.     

Impact of methanol and acetonitrile on separations based on pi-pi interactions with a reversed-phase phenyl column

Studies were performed to investigate the roles of methanol and acetonitrile on the retention mechanism of an active pharmaceutical ingredient (API) and related compounds with a reversed phase phenyl column. Different retention orders were observed depending upon whether acetonitrile or methanol was used as the organic modifier. We propose that acetonitrile impedes the selective pi-pi interactions between the analyte molecules and the phenyl groups in the stationary phase. Further study with 1-naphthoic acid and 1-naphthol as test compounds in the HPLC separation provides additional support for the influence of acetonitrile on pi-pi interactions between analyte molecules and a phenyl stationary phase. This study suggests that methanol be used as the preferred organic modifier with phenyl columns to achieve selectivity based upon pi-pi interactions.     

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.     

Synthesis and DNA binding studies of bis-intercalators with a novel spiro-cyclic linker

Threading polyintercalation has been demonstrated as a unique DNA binding mode in which a polyintercalating moiety threads back and forth through the DNA double helix. This binding topology necessitates linkers residing in both the minor and major grooves in an alternating fashion. In the present work, two novel, rigid, cis and trans oriented spiro-cyclic linkers were synthesized as potential groove binding elements in the context of threading bis-intercalation. Analysis of dissociation kinetics indicated that the cis oriented dimer has dramatically slower dissociation from poly(dGdC) and calf thymus (CT) DNA compared to the trans oriented dimer and a linear dimer control.     

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.