T-shaped Conformation Research Articles

Activation of the insulin receptor by insulin-like growth factor 2

Insulin receptor (IR) controls growth and metabolism. Insulin-like growth factor 2 (IGF2) has different binding properties on two IR isoforms, mimicking insulin’s function. However, the molecular mechanism underlying IGF2-induced IR activation remains unclear. Here, we present cryo-EM structures of full-length human long isoform IR (IR-B) in both the inactive and IGF2-bound active states, and short isoform IR (IR-A) in the IGF2-bound active state. Under saturated IGF2 concentrations, both the IR-A and IR-B adopt predominantly asymmetric conformations with two or three IGF2s bound at site-1 and site-2, which differs from that insulin saturated IR forms an exclusively T-shaped symmetric conformation. IGF2 exhibits a relatively weak binding to IR site-2 compared to insulin, making it less potent in promoting full IR activation. Cell-based experiments validated the functional importance of IGF2 binding to two distinct binding sites in optimal IR signaling and trafficking. In the inactive state, the C-terminus of α-CT of IR-B contacts FnIII-2 domain of the same protomer, hindering its threading into the C-loop of IGF2, thus reducing the association rate of IGF2 with IR-B. Collectively, our studies demonstrate the activation mechanism of IR by IGF2 and reveal the molecular basis underlying the different affinity of IGF2 to IR-A and IR-B.

Discovery of Novel 1,2,3,4-Tetrahydrobenzofuro[2,3-c]pyridine Histone Deacetylase Inhibitors for Efficient Treatment of Hepatocellular Carcinoma.

The development of histone deacetylase (HDAC) inhibitors for treating hematologic malignancies has been widely investigated, while their role in hepatocellular carcinoma (HCC) remains unexplored. In this study, we employed a scaffold-hopping design and a multicomponent synthesis approach to develop a novel series of 1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridines as HDAC inhibitors. There were a total of 29 compounds achieved with flexible linkers and zinc-binding groups, wherein compound 12k was identified as a promising candidate with good HDAC inhibitory activity, pharmacokinetic profiles, and potency. It exhibited significant therapeutic efficacy in HCC cell lines (IC50 = 30 nM for Bel-7402) and xenograft models (76% inhibition for Bel-7402 xenografts, P.O. at 20 mg/kg, QOD, for 14 days) and was found to upregulate the acetylation of histone H3 and α-tubulin, leading to apoptosis and autophagy in HCC models. Molecular docking studies indicated a unique T-shaped conformation of 12k with the catalytic domain of HDAC1. Therefore, this work provides a new structure design for HDAC inhibitors and also offers a promising treatment for HCC.

Photoisomerization of 2-Arylazoimidazoles under Visible Light: Identifying a Predictive Tool to Anticipate and Tune Likely Photoswitching Performance and Cis Half-Life.

Azopyrazoles are an emerging class of photoswitches, whereas analogous azoimidazole-based switches are unable to draw much attention because of their short cis half-lives, poor cis-trans photoreversion yields, and toxic ultraviolet (UV) light-assisted isomerization. A series of 24 various aryl-substituted N-methyl-2-arylazoimidazoles were synthesized, and their photoswitching performances and cis-trans isomerization kinetics were thoroughly investigated experimentally and theoretically. Para-π-donor-substituted azoimidazoles with highly twisted T-shaped cis conformations showed nearly complete bidirectional photoswitching, whereas di-o-substituted switches exhibited very long cis half-lives (days-years) with nearly ideal T-shaped conformations. This study demonstrates how the electron density in the aryl ring affects cis half-life and cis-trans photoreversion via twisting of the NNAr dihedral angle that can be used as a predictive metric for envisaging and tuning the likely switching performance and half-life of any given 2-arylazoimidazole. By applying this tool, two better-performing azoimidazole photoswitches were engineered. All switches permitted irradiation by violet (400-405 nm) and orange (>585 nm) light for forward and reverse isomerization, respectively, and displayed comparatively high quantum yields and impressive resistance to photobleaching.

Structural basis of the alkaline pH-dependent activation of insulin receptor-related receptor.

The insulin receptor (IR) family is a subfamily of receptor tyrosine kinases that controls metabolic homeostasis and cell growth. Distinct from IR and insulin-like growth factor 1 receptor, whose activation requires ligand binding, insulin receptor-related receptor (IRR)-the third member of the IR family-is activated by alkaline pH. However, the molecular mechanism underlying alkaline pH-induced IRR activation remains unclear. Here, we present cryo-EM structures of human IRR in both neutral pH inactive and alkaline pH active states. Combined with mutagenesis and cellular assays, we show that, upon pH increase, electrostatic repulsion of the pH-sensitive motifs of IRR disrupts its autoinhibited state and promotes a scissor-like rotation between two protomers, leading to a T-shaped active conformation. Together, our study reveals an unprecedented alkaline pH-dependent activation mechanism of IRR, opening up opportunities to understand the structure-function relationship of this important receptor.

Radiationless deactivation pathways versus H-atom elimination from the N-H bond photodissociation in PhNH2-(Py)n (n = 1,2) complexes.

Minimum energy structures of the ground and lowest excited states of aniline (PhNH2) solvated by pyridine (Py) show that the clusters formed are stabilized by hydrogen bonds in which only one or both hydrogen atoms of the NH2 group take part. Two different N-H bonds photodissociation in PhNH2-(Py)n (n = 1,2) complexes, free and hydrogen bonded have been studied by analyzing excited state potential energy surfaces. In the first one, only N-H bonds engaged in hydrogen bonding in these complexes are considered. RICC2 calculations of potential energy (PE) profiles indicate that all photochemical reaction paths along N-H stretching occur mainly via the proton-coupled electron transfer (PCET) mechanism. The repulsive charge transfer 1ππ*(CT) state dominates the PE profiles, leading to low-lying 1ππ*(CT)/S0 conical intersections and thus provide channels for ultrafast radiationless deactivation of the electronic excitation or stabilization to biradical complexes. The second photoreaction consists of a direct dissociation along the free N-H bond of the NH2 group. It has been shown that this process is played by excited singlet states of 1πσ* character having repulsive potential energy profiles with respect to the stretching of N-H bond, which dissociates over an exit barrier about 0.5eV giving rise to the formation of a 1πσ*/S0 conical intersection. This may cause an internal conversion to the ground state or may lead to H-atom elimination. This photophysical process is the same in both planar and T-shaped conformers of the PhNH2-Py monomer complex. Our findings reveal that there is no single dominating path in the photodissociation of N-H bonds in PhNH2-(Py)n complexes, but rather a variety of paths involving H-atom elimination and several quenching mechanisms.

Architecture of the human erythrocyte ankyrin-1 complex.

The stability and shape of the erythrocyte membrane is provided by the ankyrin-1 complex, but how it tethers the spectrin-actin cytoskeleton to the lipid bilayer and the nature of its association with the band 3 anion exchanger and the Rhesus glycoproteins remains unknown. Here we present structures of ankyrin-1 complexes purified from human erythrocytes. We reveal the architecture of a core complex of ankyrin-1, the Rhesus proteins RhAG and RhCE, the band 3 anion exchanger, protein 4.2, glycophorin A and glycophorin B. The distinct T-shaped conformation of membrane-bound ankyrin-1 facilitates recognition of RhCE and, unexpectedly, the water channel aquaporin-1. Together, our results uncover the molecular details of ankyrin-1 association with the erythrocyte membrane, and illustrate the mechanism of ankyrin-mediated membrane protein clustering.

Novel Bent Conformation of CD4 Induced by HIV-1 Inhibitor Indirectly Prevents Productive Viral Attachment

GSK3732394 is a multi-specific biologic inhibitor of HIV entry currently under clinical evaluation. A key component of this molecule is an adnectin (6940_B01) that binds to CD4 and inhibits downstream actions of gp160. Studies were performed to determine the binding site of the adnectin on CD4 and to understand the mechanism of inhibition. Using hydrogen–deuterium exchange with mass spectrometry (HDX), CD4 peptides showed differential rates of deuteration (either enhanced or slowed) in the presence of the adnectin that mapped predominantly to the interface of domains 2 and 3 (D2-D3). In addition, an X-ray crystal structure of an ibalizumab Fab/CD4(D1-D4)/adnectin complex revealed an extensive interface between the adnectin and residues on CD4 domains D2-D4 that stabilize a novel T-shaped CD4 conformation. A cryo-EM map of the gp140/CD4/GSK3732394 complex clearly shows the bent conformation for CD4 while bound to gp140. Mutagenic analyses on CD4 confirmed that amino acid F202 forms a key interaction with the adnectin. In addition, amino acid L151 was shown to be a critical indirect determinant of the specificity for binding to the human CD4 protein over related primate CD4 molecules, as it appears to modulate CD4′s flexibility to adopt the adnectin-bound conformation. The significant conformational change of CD4 upon adnectin binding brings the D1 domain of CD4 in proximity to the host cell membrane surface, thereby re-orienting the gp120 binding site in a direction that is inaccessible to incoming virus due to a steric clash between gp160 trimers on the virus surface and the target cell membrane.

A new Fe3+ colorimetric sensor: Nitrophenyl bispyrazole derivative synthesis using Fe3O4@SiO2@Si-Pr-NH-(CH2)2-NH2 and its DFT study

The efficient synthesis of bispyrazole derivatives was reported in the presence of Fe3O4@SiO2@Si-Pr-NH-(CH2)2-NH2 as a nanomagnetic catalyst in solvent-free conditions. The UV–Vis spectroscopy study of 4,4'-((3-nitrophenyl)methylene)bis(3-methyl-1H-pyrazol-5-ol) derivative 6a was demonstrated that it could be used as a Fe3+ ion colorimetric chemosensor, which was shown an apparent color change from white to orange with high selectivity toward the addition of Fe3+ ion in CH3CN/H2O (1:9 v/v) as a solvent. The UV–Vis absorption was increased linearly, and its detection limit was calculated 2.19 × 10−6 M.The orientations of hydroxyl groups for 5-membered and 6-membered rings of the most stable configurations of the bispyrazoles cause generation of T-shaped conformations based on Independent Gradient Model (IGM) analysis, conformational stability of the considered complexes can be related to the formation of σ-π molecular interaction heterocyclic rings which confirms with the vibrational stretching modes of hydroxyl groups and the character of the Kohn-Sham HOMO and LUMO orbitals.

Molecular Modeling and Bioinformatics Analysis of Drug-Receptor Interactions in the System Formed by Glargine, Its Metabolite M1, the Insulin Receptor, and the IGF1 Receptor

Introduction:Insulin and insulin-like growth factor type 1 (IGF1) regulate multiple physiological functions by acting on the insulin receptor (IR) and insulin-like growth factor type 1 receptor (IGF1R). The insulin analog glargine differs from insulin in three residues (GlyA21, ArgB31, ArgB32), and it is converted to metabolite M1 (lacks residues ArgB31 and ArgB32) by in vivo processing. It is known that activation of these receptors modulates pathways related to metabolism, cell division, and growth. Though, the structures and structural basis of the glargine interaction with these receptors are not known.Aim:To generate predictive structural models, and to analyze the drug/receptor interactions in the system formed by glargine, its metabolite M1, IR, and IGF1R by using bioinformatics tools.Methods:Ligand/receptor models were built by homology modeling using SWISSMODEL, and surface interactions were analyzed using Discovery Studio® Visualizer. Target and hetero target sequences and appropriate template structures were used for modeling.Results:Our glargine/IR and metabolite M1/IR models showed an overall symmetric T-shaped conformation and full occupancy with four ligand molecules. The glargine/IR model revealed that the glargine residues ArgB31 and ArgB32 fit in a hydrophilic region formed by the α-chain C-terminal helix (αCT) and the cysteine-rich region (CR) domain of this receptor, close to the CR residues Arg270-Arg271-Gln272 and αCT residue Arg717. Regarding IGF1R, homologous ligand/receptor models were further built assuming that the receptor is in a symmetrical T-shaped conformation and is fully occupied with four ligand molecules, similar to what we described for IR. Our glargine/IGF1R model showed the interaction of the glargine residues ArgB31 and ArgB32 with Glu264 and Glu305 in the CR domain of IGF1R.Conclusion:Using bioinformatics tools and predictive modeling, our study provides a better understanding of the glargine/receptor interactions.

Azomethine phthalimides fluorescent E→Z photoswitches

Herein, we report the synthesis and E→Z photoswitching behavior of two 4-substituted azomethine phthalimides containing anthracenyl and 4-(dimethylamino)phenyl moieties (EAMP1 and EAMP2). These compounds represent newly synthesized and unstudied photoswitches with dual fluorescence properties as E-isomers and at photostationary state (PSS) depending on the solvent polarity. Steady-state fluorescence measurements were performed in various solvents and the results show strong sensitivity on the environmental polarity. The kinetics of E→Z photoswitching to PSS was studied in AcCN by visible light activation at 410 nm (EAMP1) and long wavelength UV-light activation at 350 nm (EAMP2). The quantitative and qualitative performance of the switching behavior was evaluated by the degree of photoisomerization (R) and the rate constant (k). It was found for EAMP1 R = 6.95 %, k = 8.87 × 10−4 s−1 and EAMP2 R = 88.72 %, k = 4.00 × 10−4 s−1, respectively. The reason for the lower photoconversion of EAMP1 compared to the EAMP2 was analyzed through optimization of the molecular geometry of E- and Z-isomers in the ground state (S0) and first excited state (S1) by DFT/TD-DFT calculations with B3LYP/6-31+G(d,p) level of theory using IEFPCM in AcCN. It was found that E-isomers in the S0 have nonplanar conformation, while the Z-isomer of EAMP1 prefers twisted conformation and the Z-isomer of EAMP2 T-shaped conformation is energetically advantageous compared to the twisted one. The reason is the weak H…..π noncovalent interaction (NCI) between 4-(dimethylamino)phenyl moiety and phthalimide ring. Moreover, the Z-isomer of EAMP2 is unusual stable up to 600 min at room temperature in dark compared to the EAMP1, which undergoes full Z→E relaxation for less than 60 min at the same conditions. The Z→E relaxation of EAMP2 is achieved for 90 min at 60 °C. The fluorescence E→Z switching behavior was studied by emission measurements in AcCN and 1,4-DOX as E-isomers and at PSS in room and liquid nitrogen (77 K) temperatures. In the polar and nonpolar solvents, red-shifted emissions with increased fluorescence quantum (Φfl) yields have been observed at PSS compared to the E-isomers. The molecular rotor behavior was studied in the binary mixture of glycerol:ethanol and the results show a sensitivity of the emission bands depending on the environmental viscosity. Time-resolved fluorescence decay measurements were performed in AcCN and 1,4-DOX as E-isomers and at PSS to estimate the mechanism of fundamental fluorescence bands. We found that dyes at PSS have longer lifetime (τ) compared to the E-isomers, especially in less polar 1,4-DOX.

Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain.

Glucose homeostasis and growth essentially depend on the hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current understanding of insulin ligand-receptor interactions. While biochemistry predicts two distinct insulin binding sites, 1 and 2, recent structural analyses have resolved only site 1. Using a combined approach of cryo-EM and atomistic molecular dynamics simulation, we present the structure of the entire dimeric insulin receptor ectodomain saturated with four insulin molecules. Complementing the previously described insulin-site 1 interaction, we present the first view of insulin bound to the discrete insulin receptor site 2. Insulin binding stabilizes the receptor ectodomain in a T-shaped conformation wherein the membrane-proximal domains converge and contact each other. These findings expand the current models of insulin binding to its receptor and of its regulation. In summary, we provide the structural basis for a comprehensive description of ligand-receptor interactions that ultimately will inform new approaches to structure-based drug design.

Effect of Molecular Structure on the CO2 Separation Properties of Hydrophobic Solvents Consisting of Grafted Poly Ethylene Glycol and Poly Dimethylsiloxane Units

This work describes the preparation of a set of nine new novel hydrophobic PEG-substituted solvents. These solvents include linear, T-shaped, and disubstituted conformations of the PEG grafted with PDMS molecule. The effect of changing both the molecular conformation and length of PEG side arm on the physical properties and CO2 absorption capacity was studied. These solvents are intended for separation of CO2 and H2 in precombustion CO2 capture and are intended to replace the current-state-of-the-art glycol-based solvents and operate at a higher temperature. The properties of the disubstituted solvents are exceptionally well suited for precombustion CO2 capture applications because of their hydrophobicity, high CO2 solubility, low evaporation rate, and lack of foaming.

Visualization of ligand-induced transmembrane signaling in the full-length human insulin receptor.

Insulin receptor (IR) signaling plays a critical role in the regulation of metabolism and growth in multicellular organisms. IRs are unique among receptor tyrosine kinases in that they exist exclusively as covalent (αβ)2 homodimers at the cell surface. Transmembrane signaling by the IR can therefore not be based on ligand-induced dimerization as such but must involve structural changes within the existing receptor dimer. In this study, using glycosylated full-length human IR reconstituted into lipid nanodiscs, we show by single-particle electron microscopy that insulin binding to the dimeric receptor converts its ectodomain from an inverted U-shaped conformation to a T-shaped conformation. This structural rearrangement of the ectodomain propagates to the transmembrane domains, which are well separated in the inactive conformation but come close together upon insulin binding, facilitating autophosphorylation of the cytoplasmic kinase domains.

Peripheral chain length-dependent complex phase behaviour in C3-symmetric hexa-alkylated liquid crystals

ABSTRACTWe report the thermal and self-assembly properties of C3-symmetric liquid crystalline (LC) molecules consisting of a conformationally tunable triazole-based mesogen and six-fold alkyl chains. Unlike the LC compound (1) based on non-crystallisable octyl chains, 2 and 3, which have crystallisable dodecyl and tetradecyl chains, respectively, exhibit a cold crystallisation which only takes place under slow heating conditions (2°C/min). In contrast with the vertically interdigitated lamellar crystalline phase of 1, a laterally interdigitated bilayered lamellar structure driven by the crystallisation of the dodecyl or tetradecyl chains is observed in the cold crystallisation temperature range. In addition to their crystalline morphology, 2 and 3 show LC morphological behaviour distinct from that of 1, 2 and 3 exhibit a hexagonal columnar LC phase consisting of T-shaped conformers rather than the lamellar LC phase of 1. The morphological transformation from the lamellar (1) to the columnar phase (2 and 3) can be rationalised by the alleviation of the conformational energy of the longer alkyl chains. Consequently, the simple variation of alkyl chain length in the C3-symmetric LC system results in contrasting thermal and assembly properties in the crystalline and LC phases.

The role of the σ-holes in stability of non-bonded chalcogenidebenzene interactions: the ground and excited states.

The stability of the T-shaped and stacked complexes of benzene with methanethial (CH2S) and methaneselone (CH2Se) and their difluoro-, dichloro-, dibromo-derivatives is investigated in their ground and first electronic excited states by means of the SCS-ADC2 method. The origin of the stabilization in the ground state is discussed based on the results of calculations performed using the DFT-SAPT method. Calculations show that the stability of the T-shaped conformers increases upon electronic excitation, while it decreases for most of the stacked conformers. Both effects are explained by the changes in the electrostatic potential (ESP) of isolated monomers upon the electronic excitation.

Rotational spectrum and structural analysis of CH⋯F interactions in the vinyl fluoride⋯1,1-difluoroethylene dimer

The structure of the weakly bound dimer of 1,1-difluoroethylene with vinyl fluoride was studied using Fourier-transform microwave spectroscopy in the 6–19GHz range. In the observed dimer structure each monomer acts as both a weak bond donor and acceptor, giving a cyclic arrangement of CH⋯F contacts. The difluoroethylene CC bond is roughly perpendicular to the vinyl fluoride CC bond, forming the cross of a T-shaped carbon atom framework, resembling the lowest energy structure predicted by MP2/6-311++G(2d,2p) calculations. Observed CH⋯F distances are similar to those of vinyl fluoride and 1,1-difluoroethylene complexes with difluoromethane and HCCH. The dipole moment of the dimer was measured using the Stark effect, giving values of μa=0.9003(19) D, μb=0.030(8) D and μtotal=0.9008(22) D. A second ab initio structure, with the CC bonds in a slipped parallel arrangement, was predicted to be about 38cm−1 higher in energy than the T-shaped conformation. This higher energy arrangement has not been observed experimentally..

Structural characterization and physicochemical features of a new arsenate salt templated by mono and di-protonated 4-aminopyridine cations: (C5H7N2)(C5H8N2)[AsO4]·H2O

Single crystals of a new organic–inorganic hybrid compound, with the formula (4-APH)(4-APH2)[AsO4]·H2O, was synthesized at room temperature by slow evaporation method and characterized by X-ray diffraction at 150K, DSC–TG measurements, FT-IR and Raman spectroscopies. The title salt, (C5H7N2)(C5H8N2)[AsO4]·H2O, contains mono and diprotonated 4-aminopyridine cations, an arsenate trianion and one water molecule. The diprotonated 4-ammoniumpyridinium dication [C5H8N2]2+ is disordered over two positions with refined site occupancies of 0.73 and 0.27 however the monoprotonated 4-aminopyridinium cation [C5H7N2]+ is ordered. The 4-aminopyridinium rings are essentially planar and occur in stacks along b axis. In the crystal, the AsIII atom is coordinated by four O atoms in a slightly distorted tetrahedral geometry. The arsenate O atoms link the 4-aminopyridinium cations and water molecules into a three-dimensional network via intermolecular O–H···O and N–H···O hydrogen bonds. Additionally, in this structure, the different types and the nature of aromatic–aromatic interactions can distinguish between a stacked arrangement are parallel displaced and T-shaped conformation. Furthermore, the room temperature IR and Raman spectra of the title compound were recorded and analyzed. On the basis of detailed vibrational studies, the detailed assignment confirms the presence of the organic groups and the anionic entities. Besides, the thermal analysis studies have been performed, but no phase transition was found in the temperature range 298–625K. Results from X-ray crystallography, Raman, IR spectroscopy and thermal analysis are combined to provide a description of the new organic arsenate monohydrate, (C5H7N2)(C5H8N2)[AsO4]·H2O.

Conformational Preferences of π-π Stacking Between Ligand and Protein, Analysis Derived from Crystal Structure Data Geometric Preference of π-π Interaction.

π-π Interaction is a direct attractive non-covalent interaction between aromatic moieties, playing an important role in DNA stabilization, drug intercalation, etc. Aromatic rings interact through several different conformations including face-to-face, T-shaped, and offset stacked conformation. Previous quantum calculations indicated that T-shaped and offset stacked conformations are preferred for their smaller electron repulsions. However, substitution group on aromatic ring could have a great impact on π-π interaction by changing electron repulsion force between two rings. To investigate π-π interaction between ligand and aromatic side chain of protein, Brookhaven Protein Data Bank was analyzed. We extracted isolated dimer pairs with the aim of excluding multiple π-π stacking effects and found that T-shaped conformation is prevalent among aromatic interaction between phenyl ring of ligand and protein, which corresponds with the phenomenon of Phe-Phe interactions in small peptide. Specifically, for the non-substitution model, both Phe-Phe and Phenyl-Phe exhibit a favored T-shaped conformation whose dihedral angle is around 50°-70° and centroid distance is between 5.0 and 5.6 Å. However, it could be changed by substituent effect. The hydroxyl group could contact in the case of Tyr-Tyr pairs, while they point away from phenyl plane in Phe-Tyr pairs.

A phenomenological use of benzene tip to probe aromaticity

Interaction of a C–H tip of benzene with a monocyclic aromatic compound studied using M062X functional in DFT, yields a tilted T-shaped conformation with a tilt angle θ. For a set of ten monohetero five-membered rings C4H4X (X=BH, AlH, SiH2, CH2, O, S, SiH−, PH, NH, CH−), θ−1 is found to be linearly related to NICS(0), Mo-Schleyer resonance energy and Shannon’s aromaticity in excellent manners. Consequently θ can be used as an index of aromaticity of the system with which benzene is interacting. The larger the θ, the larger the aromaticity. The angle θ, which can vary from 90° to 180°, seems to have a threshold value of ∼115°; a θ value below 115° means non-aromaticity. The index shows that borazine, the inorganic benzene is aromatic. It reveals that cyclopropane is aromatic while cyclobutane is not. The present approach faces problems in polycyclic aromatic hydrocarbons as the benzene probe tends to span two adjacent rings. Finally, to test the efficacy of Truhlar’s functional M062X in DFT in describing non-bonded interactions, the case of benzene dimer has been studied. It is found that M062X/LanL2DZ or M062X/6-311++G(2d,p) can reproduce the experimental binding energy of the benzene dimer quite well, while B3LYP and BP86 cannot.

A mixed basis with off-center Gaussian functions for the calculation of the potential energy surfaces for π-stacking interactions: dimers of benzene and planar C₆.

A practical mixed basis set was developed to facilitate accurate calculations of potential energy surfaces for π-stacking interactions. Correlation consistent basis sets (cc-PVXZ) were augmented by p-type Gaussian functions placed above and below the planes of C6 moieties. Møller-Plesset (MP2, SCS-MP2) and coupled cluster [CCSD(T)] calculations show that such generated basis sets provide an accurate description of π-stacking systems with favorable computation times compared to the standard augmented basis sets. The addition of these off-center functions eliminates the linear dependence of the augmented basis sets, which is one of the most encountered numerical problems during calculation of the oligomers of polyaromatic hydrocarbons (PAH). In this work, we present a comparative study of the general characteristics of the potential energy surfaces for the parallel stacked and T-shape conformations of benzene and planar C6 clusters, using a combination of cc-PVXZ and our optimized functions. We discuss properties, such as the depth and curvature of the potential functions, short and long distance behavior, and the frictional forces between two model monomers.