Low-mode conformational search elucidated: Application to C39H80 and flexible docking of 9-deazaguanine inhibitors into PNP

We previously described a new conformational search method, termed low-mode search (LMOD), and discussed its utility for conformational searches performed on cycloalkanes and a cyclic penta-peptide. 1 In this report, we discuss a rigorous implementation of mode following (c-LMOD) for conformational searching, and we demonstrate that for a conformational search involving cycloheptadecane, this rigorous implementation is capable of finding all of the previously known structures. To the best of our knowledge, this is the first computational proof that mode following can be used for conformational searches conducted on a complex molecular system. We show, however, that, as expected, it is generally inefficient to perform a conformational search in this manner. Nonetheless, c-LMOD has been shown to be an excellent method for conducting conformational analyses involving conformational interconversions, where the location of saddle points is important. We also describe refinement to our original LMOD procedure (l-LMOD) and discuss its utility for a difficult conformational search problem, namely locating the global minimum energy conformation of C₃₉H₈₀. For this search, l-LMOD combined with limited torsional Monte Carlo movement was able to locate the lowest energy structures yet reported, and significantly outperformed a pure torsional Monte Carlo and a genetic algorithm-based search. Furthermore, we also demonstrate the utility of l-LMOD combined with random translation/rotation of a ligand for the extremely difficult problem of docking flexible ligands into flexible protein binding sites on a system that includes 9-deaza-guanine-based inhibitors docked into the flexible biding site of PNP. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1671–1684, 1999     

Variations on the theme of closest packing: The structural chemistry of barium titanate compounds

The crystal structures of most barium titanates can be described as hexagonal closest packings consisting of atoms of Ba and O and of vacancies between them. The pseudohexagonal cell constants of these compounds are close to the ideal hexagonal values. The most common stacking is the six-layer sequence (hcc)₂. The mean diameter of a closest packed particle in these packings is 2.85 Å, while the mean thickness of a layer is 2.33 Å. The recognition of this closest packing principle has been helpful in the solution of many of the crystal structures of this group. With the exception of BaTi₄O₉, all the barium titanates which are usually classified as tunnel structures or Wadsley-Andersson phases can be described as cubic closest packings. The deviations of the pseudocubic phases from the ideal cubic values are larger than in the pseudohexagonal cases. A few of the barium titanates are related to the so-called 3.0-Å phases based on the rutile-type octahedral chain. These structures are characterized by having two almost closest packed corrugated layers at right angles to each other. The structures of a number of compounds in which the Ti⁴⁺ atoms are replaced partly by Ti³⁺, Al, Pt⁴⁺, or Li are based on principles similar to those of the barium titanates proper. The mean TiO distances in the coordination octahedra of the barium titanates depend strongly on the distortions of the octahedra.     

cis‐Dicarbonyl‐cis‐dichlorido‐trans‐bis(triphenylphosphine‐κP)iridium(III) tetrafluoridoborate,formed by reaction of (cycloocta‐1,5‐diene)bis(triphenylphosphine)iridium tetrafluoridoborate with carbonyl fluoride in dichloromethane solution

The reaction between carbonyl fluoride and [Ir(COD)(PPh₃)₂]BF₄ (COD is cycloocta‐1,5‐diene) in dichloromethane solution affords the novel title iridium salt, [IrCl₂(C₁₈H₁₅P)₂(CO)₂]BF₄. The cation lies across a twofold rotation axis in the space group P2₁2₁2 and its structure confirms the presence in a cis relationship of two metal‐bound chlorides, while the phosphine ligands occupy a trans pair of sites. The anion also lies across a twofold rotation axis, and the F atoms are disordered over two sets of sites.     

N,N′‐Dithiobisphthalimide–1,4‐dioxan (1/0.6): a C2/c solvate with disordered solvent molecules localized in channels

N,N′‐Di­thio­bisphthal­imide crystallizes from 1,4‐dioxan solution as a solvate, 3C₁₆H₈N₂O₄S₂·1.8C₄H₈O₂, having space group C2/c. Four of the 12 C₁₆H₈N₂O₄S₂ mol­ecules in the unit cell lie on twofold rotation axes, while the other eight lie in general positions. These mol­ecules are linked by aromatic π–π‐stacking interactions and by C—H?O hydrogen bonds to form a framework enclosing continuous channels running parallel to the [101] direction, which account for ca 20% of the unit‐cell volume. The dioxan mol­ecules lie in these channels disordered across two sets of sites, with one set across an inversion centre and the other across a twofold rotation axis.     

Polymorphs of DABCO monohydrate as structural analogues of NaCl

A new crystalline form of 1,4‐diazabicyclo[2.2.2]octane (DABCO) monohydrate, C₆H₁₂N₂·H₂O, crystallizing in the space group P3₁, has been identified during screening for cocrystals. There are three DABCO and three water molecules in the asymmetric unit, with two DABCO molecules exhibiting disorder over two positions related by rotation around the N...N axis. As in the monoclinic C2/c (Z′ = 2) polymorph, the molecular components are connected via O—H...N hydrogen bonds into a polymeric structure that consists of linear O—H...N(CH₂CH₂)₃N...H—O segments, which are approximately mutually perpendicular. The two polymorphic forms of DABCO monohydrate can be considered as structural analogues of NaCl, with the nearly globular DABCO molecules showing distorted cubic closest packing and all octahedral interstices occupied by water molecules.     

Reversible phase transition of 2‐carboxypyridinium perchlorate–pyridinium‐2‐carboxylate (1/1)

The title salt, C₆H₆NO₂⁺·ClO₄⁻·C₆H₅NO₂, was crystallized from an aqueous solution of equimolar quantities of perchloric acid and pyridine‐2‐carboxylic acid. Differential scanning calorimetry (DSC) measurements show that the compound undergoes a reversible phase transition at about 261.7 K, with a wide heat hysteresis of 21.9 K. The lower‐temperature polymorph (denoted LT; T = 223 K) crystallizes in the space group C2/c, while the higher‐temperature polymorph (denoted RT; T = 296 K) crystallizes in the space group P2/c. The relationship between these two phases can be described as: 2a_RT = a_LT; 2b_RT = b_LT; c_RT = c_LT. The crystal structure contains an infinite zigzag hydrogen‐bonded chain network of 2‐carboxypyridinium cations. The most distinct difference between the higher (RT) and lower (LT) temperature phases is the change in dihedral angle between the planes of the carboxylic acid group and the pyridinium ring, which leads to the formation of different ten‐membered hydrogen‐bonded rings. In the RT phase, both the perchlorate anions and the hydrogen‐bonded H atom within the carboxylic acid group are disordered. The disordered H atom is located on a twofold rotation axis. In the LT phase, the asymmetric unit is composed of two 2‐carboxypyridinium cations, half an ordered perchlorate anion with ideal tetrahedral geometry and a disordered perchlorate anion. The phase transition is attributable to the order–disorder transition of half of the perchlorate anions.     

An Unexpected Atropisomerically Stable 1,1‐Biphenyl at Ambient Temperature in Solution,Elucidated by Vibrational Circular Dichroism (VCD)

Biphenyls with only two substituents at the ‘peri'‐position normally show rotation about their chiral axis at room temperature. Using vibrational circular dichroism (VCD), we found no evidence for rotation of (P)‐2′‐[(4S)‐4,5‐dihydro‐4‐(1‐methylethyl)oxazol‐2‐yl][1,1′‐biphenyl]‐2‐methanol ((P,S)‐ 1 ) in CDCl₃ about its chiral axis due to stabilization by intramolecular H‐bonding. All rotamers of 1 were calculated at the DFT level, and, from these optimized structures, the VCD spectra were calculated and compared to the measured VCD spectra. The best agreement between calculated and measured spectra is obtained when two rotamers are present in solution. These rotamers differ primarily in their intramolecular H‐bonding interactions, having either OH???N (the form present in the solid state) or OH???O H‐bonds, i.e., a rotation of the heterocycle in 1 takes place in solution.     

Torsional symmetry dependence of S1 dynamics in molecules that undergo methyl internal rotation

The single‐rovibronic‐level fluorescence of “intermediate‐case” molecules that undergo methyl internal rotation is strongly influenced by the torsional symmetry of the lowest excited singlet state (S₁). The most dramatic example of such symmetry dependence comes from our recent finding that the intensities of the e–e transitions in the high‐resolution S₁←S₀ fluorescence excitation spectra of jet‐cooled acetaldehyde become very weak relative to the a–a transitions at higher beam temperatures. In this study, we rationalize this remarkable torsional symmetry dependence of electronic relaxation in acetaldehyde on the basis of internal‐overall rotation coupling that leads to symmetry‐selective increase in the density of states for singlet‐triplet coupling. Related observations by others on aliphatic carbonyls and diazabenzenes are also discussed within the context of the coupling between the internal and overall rotation. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 71: 167–176, 1999     

The molecular structure of tetracarbonylhydrido(1,1,4,4-tetraphenyl-1,4-diphosphabutane)vanadium(+I), HV(CO)4(Ph2PCH2CH2PPh2)

Summary The crystal and molecular structures of the title compound have been determined. The compound crystallizes in the orthorhombic space group Pcab witha = 1463.3(30),b = 1663.1(36),c = 2250.1(47) pm and Z = 8. The molecular structure is best described as a distorted pentagonal bipyramid, the hydride ligand lying in a plane formed by vanadium, the two phosphorus atoms and two carbon monoxide groups. The V-H bond length is 155.2(93) pm, and the distance between H^– and the nearest phosphorus atom is 157.9(118) pm. In solution, HV(CO)₄Ph₂P(CH₂)₂PPh₂ appears to be fluxional.     

Crystal Structures of Two Modifications of [3,O-didehydro-mebmt1, val2]-cyclosporin and comparison of three different X-ray data sets

The crystal structure of [3,O-didehydro-MeBmt¹, Val²]cyclosporin (PSC-833; 1 ) was investigated by X-ray analysis. Data were collected from two different crystal modifications. Modification I crystallizes in P3₁21, a = b = 21.419 (2) Å, c = 32.101 (3) Å with one molecule in the asymmetric unit, modification II in P3₂21, a = b = 21.313 (2) Å, c = 62.053(3) Å with two molecules per asymmetric unit. This non-immunosuppressive analogue of cyclosporin A adopts a similar backbone conformation to that found in the crystal structure of cyclosporin A and other analogues. Three different data sets of modification I were collected using an Enraf-Nonius-CAD4 diffractometer with CuK_α radiation at 20°, a Stoe-Siemens four-circle diffractometer with MoK_α radiation at ? 120°, and an EMBL image-plate scanner with synchrotron radiation at 12°. The quality of the data sets was evaluated by internal consistency, independent structure solution, and refinement. The structural parameters reported here for modification I are based on the synchrotron data.     

Comparison of basis set superposition error corrected perturbation theories for calculating intermolecular interaction energies

Recently, two different but conceptually similar basis set superposition error (BSSE) free second‐order perturbation theoretical schemes were developed by us that are being based on the chemical Hamiltonian approach (CHA). Using these CHA‐MP2 and CHA‐PT2 methods, a comparison is made between the a posteriori and a priori BSSE correction schemes at the correlated level. Sample calculations are presented for four hydrogen bonded complexes (HFH₃N, HFH₂O, H₂SHF, and H₂OHCl) in nine different basis sets (from 6–31G to TZV**++). The results show that the BSSE content is very significant in the interaction energy if electron correlation is accounted for, so removing the BSSE is very important. The differences of the two perturbational theories discussed are connected solely with the different one electron orbital sets used for building up the unperturbed single determinant wave function. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 274–283, 1999     

cis‐Diaqua­bis[(E)‐4‐(2‐hydroxy­benzyl­idene­amino)benzoato‐κ2O,O′]cadmium(II): two‐dimensional layers built from strong O—H⋯O hydrogen bonding in the coordination sphere

In the title compound, [Cd(C₁₄H₁₀NO₃)₂(H₂O)₂], which crystallizes with Z = 4 in the space group C2c, the Cd atom is located on a twofold rotation axis and coordinated by six O atoms from two water mol­ecules and two carboxylate groups of two planar 4‐(2‐hydroxy­benzyl­idene­amino)­benzoate lig­ands, with a dihedral angle of 85.6 (1)° between them. Strong O—H⋯O hydrogen bonding in the coordination sphere, together with π–π stacking inter­actions, assemble the mol­ecules into two‐dimensional layers.     

电化学还原合成1,5-二氨基萘

研究了以1,5-二硝基萘为原料电化学还原合成1,5-二氨基萘的反应. 室温下, 运用循环伏安法研究了1,5-二硝基萘的循环伏安行为, 1,5-二硝基萘的还原是一受扩散控制的不可逆反应; 循环伏安图上两个连续的还原峰对应于两个硝基的还原; 求出了反应的传递系数α₁在0.275～0.335之间, α₂在0.360～0.437之间. 探讨了电解电位(E)、底物浓度(c₁)、电解电量(Q)、硫酸浓度(c₂)以及溶剂(DMF)与水的体积比(Y)对产物产率的影响, 在最优条件下1,5-二氨基萘的产率最高可达77%.     

Substituent effects on the disproportionation‐combination rate constant ratios for gas‐phase halocarbon radicals. IV. Reactions of ·CF3 + CF3CH2CF2· and CF3CH2CF2· + CF3CH2CF2·

Rate constant ratios, k_d/k_c, for the disproportionation/combination reaction at a temperature of 295 ± 2 K, have been measured as 0.034 ± 0.009 for the collision between CF₃CH₂CF₂ + CF₃ radicals and as 0.075 ± 0.019 for CF₃CH₂CF₂ + CF₃CH₂CF₂ radicals. The effect of the two fluorine substituents on the rate constant ratio is compared to previous k_d/k_cs with CF₃CH₂CH₂, CF₃CH₂CHCl, and CF₃CH₂CHCF₃ radicals. © 1999 John Wiley & Sons, Inc. Int J Chem Kinet: 31: 237–243, 1999     

Determination of the Atropisomeric Stability and Solution Conformation of Asymmetrically Substituted Biphenyls by Means of Vibrational Circular Dichroism (VCD)

Vibrational‐circular‐dichroism (VCD) studies of the solution conformations of three 2,2′‐substituted biphenyls are reported. Biphenyls with only two substituents at the peri‐position normally show rotation about their central axis of chirality at room temperature in solution. We previously found no evidence for rotation of (P,4S)‐2‐[4,5‐dihydro‐4‐(1‐methylethyl)oxazol‐2‐yl]‐2′‐(hydroxymethyl)‐1,1′‐biphenyl ( 1 ) in CDCl₃ about its 1,1′‐ axis, due to stabilization by intramolecular H‐bonding and the presence of the i‐Pr substituent, but two conformers were found in solution that result from rotation of the heterocycle in 1 between OH⋅⋅⋅N (the form present in the solid state) and the OH⋅⋅⋅O H‐bonded forms, with no rotation of the i‐Pr group or (P) → (M) twist [1]. For (P,S)‐ 2 , where the i‐Pr substituent of 1 has been replaced by a Ph group, rotation of the heterocycle takes place in CDCl₃ solution. For (P,S)‐ 3 and (M,S)‐ 4 , where Me substitution at the two 6,6′‐positions of (P,S)‐ 1 prevents rotation about the central axis of chirality, rotation of the heterocycle is observed for the (P)‐configuration ((P,S)‐ 3 ), but not for the (M)‐configuration ((M,S)‐ 4 ). Only one rotamer involving the i‐Pr group, which was found in the solid state of (P,S)‐ 3 , was also observed in solution, but (M,S)‐ 4 , obtained as an oil, was found to be a mixture of three rotamers of the i‐Pr group.     

Ferroelectric properties of nylon 11 and poly(vinylidene fluoride) blends

Both poly(vinylidene fluoride) (PVF₂) and nylon 11 are ferroelectric polymers, and have been extensively studied over the past two decades. Blend films were made from mixed powders of these two polymers, which were then melt pressed and cold drawn. The ferroelectric properties of these blend films were investigated. The remnant polarization, P_r, was found to vary with composition, and to be 60% larger than that of either component at a 50/50 (by weight) composition where P_r exhibited a maximum of about 90 mC/m². The magnitude of the coercive field, E_c, also exhibited a maximum at this composition. Both P_r and E_c are also observed to change significantly with the draw ratio. The results are discussed based on a two-phase dielectric composite model. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 3217–3225, 1999     

MRD-CI potential surfaces using balanced basis sets. VI. Correlation of bond order with bond function composition for first-row diatomic molecules

This article presents theoretical calculations on bond energies for the first-row diatomics C₂, CN, CO, CF, N₂, NO, NF, O₂, FO, and F₂, which vary in bond order from one to three. The atomic-centered basis functions are systematically augmented with bond functions (BFs), which range in composition from (sp) to 2(spd), to determine the basis set which yields a dissociation energy closest to the experimental D_e. A strong correlation is found to exist between the bond order and the number of BFs required in the optimum basis set. Based on these results, we are able to predict the optimum composition of the BF basis which should be added to a DZP-quality AO basis set for a case in which only the bond order is known. These optimized BF basis sets are shown in the accompanying article to give more accurate potential curves than larger basis sets without bond functions.     

THE CRYSTAL AND MOLECULAR STRUCTURE OF BIS(p-NITROPHENACETURO)DIAQUOCOPPER(II)

Abstract

The crystal and molecular structure of [Cu(p-NO₂C₆ H₅CH₂CONHCH₂CO₂)₂ (H₂O)₂] has been determined by single-crystal, x-ray diffraction techniques. The compound is centrosymmetric crystallizing in a monoclinic unit cell (P2₁/c) with two molecules per unit cell. The cell dimensions are: a = 11.588(1)A, b = 11.405(1)A, c = 8.041(1)Å and β = 93.47 · (1). The structure was solved by Patterson methods and refined to a value of R = 0.063. The coordination about the copper assumes an unexpected square planar geometry in which two phenaceturic moieties are each coordinated through the carboxylic oxygen (Cu—O = 1.933A) and the two waters complete the coordination (Cu—O_w = 1.959Å). The overall conformation of the phenaceturic acid is retained although there is a rotation of 180° about the peptide C—N bond.     

Development of the resolution theory for electrophoretic exclusion

Electrophoretic exclusion, a technique that differentiates species in bulk solution near a channel entrance, has been demonstrated on benchtop and microdevice designs. In these systems, separation occurs when the electrophoretic velocity of one species is greater than the opposing hydrodynamic flow, while the velocity of the other species is less than that flow. Although exclusion has been demonstrated in multiple systems for a range of analytes, a theoretical assessment of resolution has not been addressed. To compare the results of these calculations to traditional techniques, the performance is expressed in terms of smallest difference in electrophoretic mobilities that can be completely separated (R = 1.5). The calculations indicate that closest resolvable species (Δμ_min) differ by approximately 10^?13 m²/Vs and peak capacity (n_c) is 1000. Published experimental data were compared to these calculated results.