Skewed Conformation Research Articles

Solvent effect on the conformation of Benzil

The conformation of benzil is investigated by PM3 and density functional theory (B3LYP) combined with the 6-31G(d,p) basis set. The variation of the relative energy with the OC–CO torsion angle indicates only one rather flat minimum, reflecting the flexibility of the benzil molecule. The dipole moment is measured in several organic solvents of various polarity and the IR and Raman spectra investigated in the CO stretching region in the same solvents. The torsional OC–CO angle is evaluated from the dipolar and vibrational data. The results indicate that, in all the solvents, benzil is in a skewed conformation, the cisoid conformation being slightly favoured when the polarity of the solvent increases. The contribution of electrostatic and specific interactions to the reduction of the torsional angle is discussed.

Structures and related properties of AgX bearing 3,3'-thiobispyridine (X- = NO3-, BF4-, CLO4-, and PF6-.

Infinite molecular helices [Ag(3,3'-Py2S)]X (3,3'-Py2S = 3,3'-thiobispyridine; X- = BF4-, ClO4-, and PF6-) have been rationally constructed or induced. Crystallographic characterization (X- = BF-, monoclinic P2(1)/n, a = 8.946(3) A, b = 14.130(2) A, c = 10.124(2) A, beta = 107.83(2) degrees, V = 1218.3(5) A3, Z = 4, R = 0.0351; X- = ClO4-, monoclinic P2(1)/n, a = 8.884(1) A, b = 14.305(3) A, c = 10.110(1) A, beta = 106.78(1) degrees, V = 1230.1(3) A3, Z = 4, R = 0.0417; X- = PF6-, monoclinic P2(1)/c, a = 10.959(2) A, b = 9.808(2) A, c = 14.065(3) A, beta = 112.03(2) degrees, V = 1401.4(5) A3, Z = 4, R = 0.0442) reveals that the skeletal structure is an oblong cylindrical cationic helix consisting of alternating Ag(I) and 3,3'-Py2S species and that its counteranions are pinched in two columns inside each helix. The formation of the helical coordination polymer appears to be primarily associated with a suitable combination of the skewed conformer of 3,3'-Py2S and the potential linear geometry of the N-Ag(I)-N bond. However, the framework of the nitrate analogue [Ag(3,3'-Py2S)NO3] (monoclinic P2(1)/c, a = 8.177(2) A, b = 10.291(1) A, c = 14.771(2) A, beta = 102.19(1) degrees, V = 1214.9(4) A3, Z = 4, R = 0.0300) is a two-dimensional network consisting of an 18-membered ring unit, where each 3,3'-Py2S acts as a N,N',S- tridentate ligand connecting three tetrahedral silver(I) ions with the monodentate nitrate weakly bonded to the silver (Ag.O = 2.65(1) A) rather than acting as a counteranion. The anion exchange of [Ag(3,3'-Py2S)NO3] with BF4-, ClO4-, or PF6- has been accomplished in aqueous media. The two-dimensional networks are easily converted into the helices via the anion exchange, but the reverse anion exchange proceeds slightly. Thermal analyses indicate a relationship between the thermal stabilities and the structural properties.

Conformational Equilibrium of 4-Hydroxy- and 4-Acetoxy-4-(3-aryloxy-1-propynyl)-1-(2-ethoxyethyl)piperidinium Salts in Solution

4-Hydroxy- and 4-acetoxy-4-(3-aryloxy-1-propynyl)-1-(2-ethoxyethyl)piperidine hydroclorides in aprotic solvents give rise to equilibrium mixtures of two epimers. In the case of the acetoxy derivatives (in CDCl3) the equilibrium is displaced toward the “less stable” epimer. This may be due to considerable contribution of the skewed boat conformer with intramolecular hydrogen bond.

Microtubules switch occasionally into unfavorable configurations during elongation

Tubulin assembles to form a range of structures that differ by their protofilament and monomer helix-start numbers. The microtubule lattice is believed to accommodate these different configurations by skewing the protofilaments so that the lateral interactions between tubulin subunits are maintained. Here, we present the characterization of 14 types of microtubules, including six novel ones, through an extensive analysis of microtubules assembled in vitro from pure tubulin. Although the six new types represented only 1 % of the total length of the population examined (∼17 mm), they define the limits of microtubule structure and assembly. Protofilament skewing is restricted to within ±2 °. Outside this range, the restoring force induced by the skewed protofilaments is compensated by a longitudinal shift (less than ±0.2 nm) between adjacent protofilaments. Configurations with theoretical protofilament skew angles larger than ±4 ° or that necessitate larger modifications of the microtubule surface lattice were not observed. Analysis of the microtubule types distribution reveals that it is sharply peaked around the less skewed conformations. These results indicate that both the flexibility of the protofilaments and the strength of their lateral interactions restrict the range of structures assembled. They also demonstrate that growing microtubules can occasionally switch into energetically unfavorable configurations, a behavior that may account for the stochastic nature of catastrophes.

Conformations and rotational barriers of 2,2′-bi-1H-imidazole Semiempirical, ab initio, and density functional theory calculations

Conformations and rotational barriers of 2,2′-bi-1H-imidazole (1) have been investigated by using semiempirical, ab initio, and density functional theory (DFT) calculations. All theoretical methods employed in this study agree that the trans conformation of 1 is the global minimum, and the cis conformation is a transition state. Although semiempirical methods have located only these two stationary points, ab initio and DFT calculations have found additional local minima at a slightly skewed cis conformation. The torsional angle between two imidazole ring planes at these local minima is calculated to be 26.3° at HF/3-21G, 45.9° at HF/6-31G*, and 37.8° at B3LYP/6-31G*. Our best estimate for the overall rotational barrier of 1 through the cis conformation is 11.8 kcal mol -1 , which is obtained from B3LYP/6-31G* calculations with the correction of zero-point vibrational energy. Estimations of this barrier by semiempirical methods are significantly lower than 8.6 kcal mol -1 by AM1, and 10.6 kcal mol -1 by PM3, while the overall rotational barriers predicted by the SCF methods (15.6 and 13.6 kcal mol -1 at the HF/3-21G and HF/6-31G* levels, respectively) are considerably higher than the B3LYP/6-31G* result. In order to better understand the origins of the rotational barrier, we have attempted to analyze (1) changes of the electrostatic potential maps and the V min (r) values, (2) Fourier expansion terms for rotational potential energy functions, and (3) the bond length change during internal rotation. Based on these analyses, electrostatic interaction and π-conjugation appear to play an important role in forming the shape of the rotational barrier.

Homobinuclear bis-3,6-di-tert-butyl-o-benzosemiquinone and bis-3,6-di-tert-butyl-o-catecholate complexes of PdII and PtII with bridging ligands. Molecular structure of (3,6-Cat)2Pd2L2 (L = dppm and dppy)

Reactions of the binuclear complexes M2L2Cl2 [M = Pt or Pd, L = bis(diphenylphosphino)methane (dppm) or 2-(diphenylphosphino)pyridine (dppy)] with thallium 3,6-ditert-butyl-o-benzosemiquinone (3,6-SQ) in solutions have been studied. The formation of the corresponding bis(semiquinone) binuclear derivatives M2L2(SQ)2 with retention of the metal-metal bond has been established by the ESR method. The average distances between the centers of localization of unpaired electrons, which were determined from the ESR spectral data for the complexes studied, allow conclusions about the parallel arrangement of the semiquinone ligands in skewed conformations in a square-pyramidal coordination sphere of both metal atoms. At room temperature, the biradical complexes are slowly converted to diamagnetic catecholate compounds with cleavage of the M-M bond and with retention of the bridging structure of the dppm and dppy ligands. The structures of catecholate complexes of palladium have been established by X-ray structural analysis.

Ab initio MO study of diphenylamine derivatives: diphenylamine, diphenylaminium, diphenylaminyl and diphenylnitroxide

The electronic structures of four diphenylamine derivatives: diphenylamine, diphenylaminium, diphenylaminyl and diphenylnitroxide, often used in ferromagnetic model-polymers as a spin accommodator, are described using ab initio molecular orbital methods in the RHF, UHF and ROHF schemes at the STO-3G and 6–31G levels of calculation. The four ‘skewed’, ‘planar’, ‘book’ and ‘morino’ conformations related to the torsional motion characteristic of diphenyl molecules are examined in detail on the basis of the present calculations. The skewed conformation is predicted to be the most favourable of these molecules. The calculated geometrical parameters are in good agreement with the experimental results already reported.

Ground and excited states of benzil: A theoretical study

The ground and low-lying excited state potential energy curves of benzil have been studied. The ground state geometry is fully optimized by the AM1 method. The excited states are calculated by using the CNDO/S-CI method. The calculations confirm that benzil in the ground state has a skewed conformation whereas the first excited singlet and triplet states of this molecule are trans-planar. The geometry relaxation in the excited states of benzil agrees well with the experimental findings. The absorption and emission bands of benzil have been compared with the observed bands. The dipole moments of the ground and excited states at some conformations are also reported. The effect of solvents on the electronic states of benzil has been studied using the continuum dielectric model.

Stereochemistry of benzodiazepinooxazoles: crystal structure and NMR spectroscopic investigations of new conformational variants of mexazolam analogues

The varied stereochemistry of mexazolam analogues is described on the basis of six crystal-structure analyses of the 11b-hydro (2), methyl (3 and 4), phenyl (5) and 2′-chlorophenyl (6; mexazolam) derivatives of 3-methylbenzodiazepinooxazole and the benzodiazepinooxazole (1), all determined by X-ray diffraction techniques. Two new comformations for the benzodiazepinooxazole ring system have been found in these analyses, i.e., a flat conformation YII in the case of 2 and 3, and a skewed conformation YI in 1. The usual ‘boat-wing’ conformation XI has been found in compounds 4–6. The solution-state 1H NMR spectra of 1, 3 and 4 at room temperature have been examined by phenyl ring-current effects and support retention of the three types of solid-state conformation. In polar solvents, all these compounds (except for 1) show a diastereoisomeric equilibrium of trans↔cis interconversion through epimerization at the 11b position. The diastereoisomeric and conformational differences in these compounds are discussed along with the steric interaction of the substituents.

An NMR and theoretical study of the conformation and internal flexibility of butaclamol hydrochloride

A theoretical (MM2) and experimental (1H and 13C NMR) study of butaclamol hydrochloride in CDCl3 has been done in order to determine preferred conformations and internal molecular flexibility of this molecule. The theoretical calculations suggest the presence of four low-energy conformations, two of which involve a trans junction of the D and E rings, with the other two involving a cis I ring junction. An alternative cis junction (cis II) was excluded on energetic grounds. The 1H NMR data strongly suggest the presence of a trans D-E ring junction and are consistent with a chair conformation of the E ring. 13C spin-lattice relaxation time measurements show that most of the molecule is rigid, although there is some degree of mobility in the seven-membered B ring, associated with rapid flipping of the bridging C8 and C9 carbons between two skewed conformations, which have previously been referred to as conformer A and conformer B (Laus et al. Heterocycles 1984, 22, 311).

Electronic structure of conducting polymers with nonconjugated backbones: 1,4-polybutadiene and 1,4-polyisoprene

Through MNDO geometry optimizations and VEH band-structure calculations on both cis- and trans-polybutadiene and polyisoprene, it is shown that the polymers with skewed conformations possess an HOVB width on the order of 0.79-0.93 eV. The solid state ionization potentials are found to be too large to allow for oxidation by iodine and formation of ethylenic radical cations

Die sterisch gehinderte Rotation um die C–C–Bindung eines acyclischen α,β‐ungesättigten Ketons: 2,2,5‐Trimethyl‐4‐isopropylhex‐4‐en‐3‐on

Eine Aktivierungsbarriere von 45 kJ mol−1 folgt aus den 1H‐NMR‐Spektren für die erste nachgewiesene gehinderte Rotation um die sp2‐sp2‐Einfachbindung eines acyclischen α,β‐ungesättigten Ketons (1). Die Intensitäten der UV‐Banden der π → π*‐ und n → π*‐Übergänge sind mit einer verdrillten Konformation von 1 in Einklang. Molekülmechanikrechnungen lassen allerdings eine deutlich höhere Aktivierungsbarriere erwarten, was die schlechte Parametrisierung für sp2‐sp2‐Einfachbindungen belegt.magnified image

Sterically Hindered Internal Rotation in an Acyclic α,β‐Unsaturated Ketone. 2, 2, 5‐Trimethyl‐4‐isopropylhex‐4‐en‐3‐one

An activation barrier of 45 kJ mol−1 follows from the 1H-NMR spectra in the case of the first detected hindered rotation about the sp2—sp2 single bond of an acylic α,β-unsaturated ketone (1). The intensities of the UV bands of the π→π* and n → π* transitions are consistent with a skewed conformation of 1. However, molecular mechanics calculations predict a much higher steric barrier than is observed, which demonstrates the limitations of our current understanding of sterically hindered rotation about sp2—sp2 single bonds in aliphatic systems.

Solid state polymerization of diacetylenes

An X-ray structural study (R = 0.043 for 2704 reflections) of C24H30N2O4 was carried out. The molecule has a skewed conformation, the piperidine cycles are in a chair conformation. The N atoms of paramagnetic groups exhibit different degrees of pyramidalization, due to crystal packing effects, their displacements from the planes of three bonded atoms being 0.111 and 0.042(2) Å. The H-bonds of the O – H … O type link the molecules into layers parallel to the ac-plane. The molecules do not form characteristic stacking necessary for the topochemical solid state polymerization. This fact is in good agreement with the observed inertness of the crystals with respect to the solid state polymerization.

Properties of C and Oprotonated formaldonitrone

C and Oprotonated formaldonitrone was studied at the 6–31G*//6–31G* level of Hartree—Fock theory. The Oprotonated formaldonitrone was found to exist in an unexpected skewed conformation which was found to be 23.9 kcal mol −1 more stable than Cprotonated formaldonitrone. A high barrier of 96.9 kcal mol −1 was found to exist for the antarafacial 1,3-hydrogen migration between the C and Oprotonated formaldonitrones.

Thyroid hormone structure-activity relationships: molecular structure of 3,5,3'-triiodothyropropionic acid.

The crystal and molecular structures of 3,5,3'-triiodothyropropionic acid (T3P), determined as an N-diethanolamine salt, were carried out and the results are compared with those of other thyroid hormone structures. These data show that T3P has an unusual conformation with the diphenyl ether bridge outside the range normally observed for other thyroactive acid structures and has the largest deviations from the ideal skewed conformation predicted for 3,5-diiodothyroactive compounds. These conformational properties are not observed in the structures of thyroformic or acetic acid analogues. Biochemical data indicate that thyropropionic acid analogue activity differs from that other acid analogues which could imply that their metabolism and activity can be controlled differently from that of other hormone metabolites.

Lewis-base adducts of Group 11 metal(I) compounds. Part 28. Solid-state phosphorus-31 cross-polarization magic-angle spinning nuclear magnetic resonance and structural studies on the mononuclear 3: 1 adducts of triphenylphosphine with copper(I) halides

Solid-state cross-polarization magic-angle spinning 31P n.m.r. data and single-crystal X-ray diffraction structure determinations are reported for solvated and unsolvated 3 : 1 adducts of triphenylphosphine with copper(I) halides, [Cu(PPh3)3X]. The structures of the unsolvated bromide and iodide complexes are isomorphous with the previously studied chloride analogue, crystallizing in the trigonal space group P3 with three independent molecules each disposed about a crystallographic three-fold symmetry axis. Two of the molecules are related by a pseudo-inversion centre. The PPh3 ligands adopt a skewed conformation about Cu–P with respect to Cu–X [X–Cu–P–C(l11) angles 30.6–34.1 °]. The Cu–P distances are not halide dependent [Br, 2.351(4), 2.340(4), and 2.369(4)A; I, 2.362(3), 2.346(5), and 2.357(5)A] and all P–Cu–P angles are close to the tetrahedral value. Solid-state 31P n.m.r. spectra of each halide reveal two symmetric quartets in an intensity ratio of 2: 1; average chemical shifts overall are –10, –13, and –17 p.p.m. for X = Cl, Br, and I respectively. The splittings within each quartet are also halide independent ranging between 900 and 940 Hz. The high intensity quartet is assigned to the two enantiomerically related molecules. The acetone solvated structures crystallize in the triclinic space group P with the bromide and iodide isomorphous. Solvation changes the conformation of the PPh3 ligands about Cu–P from skewed to staggered, with X–Cu–P–C(l11) 45.5–56.3°. The potential increase in back strain because of this conformational change is relieved by an increase of ∼ 5° in the P–Cu–P angles. The Cu–P and P–Cu–P bond lengths and angles again do not change significantly with halogen within the series. The solid-state 31P n.m.r. spectra each reveal a single quartet shifted downfield by 6–10 p.p.m.; the quartets are slightly more asymmetric than in the trigonal phase with splitting values lying in the range 890–980 Hz.

Molecular structure of thyroxine analogues. Crystal structure of 3,5,3'-triiodothyroacetic and 3,5,3',5'-tetraoiodothyroacetic acid N-diethanolamine (1:1) complexes.

Crystallographic data demonstrated that conformations of thyroid hormones and their derivatives in which the phenyl rings are either skewed (phi,phi'; +/-90,0 degrees) or twist-skewed (phi,phi'; +/-108, +/-28 degrees) are energetically favored. Acetic acid metabolites are consistently observed in the skewed conformation whereas their parent hormones are observed in the twist-skewed conformation. These preferences are manifestations of long-range conformational transmission and together with plasma protein binding data may indicate a site-specific preference for the skewed vs. twist-skewed conformation. These findings result in part from the crystal structure determinations of the N-diethanolamine (1:1) complexes of the active thyroxine metabolites 3,5,3'-triiodothyroacetic acid (T3AA) and 3,5,3'5'-tetraiodothyroacetic acid (T4AA) which are reported here. The conformation of the 3'-iodine in the hypocholestermic agent T3AA is distal, the biologically preferred conformation, and the overall conformation of T3AA is transoid, while that of T4AA is cisoid.

Conformation of unsymmetrical diaryl disulfides

1. In solution the unsymmetrical p-substituted diaryl disulfides have a skewed conformation with a dihedral angle of ∼80°. 2. The angles of rotation of the aryl fragments relative to the planes of the Car-S-S bonds in the molecules of different compounds depend on the nature of the p-substituents.

Biopolymer — Small Molecule Interactions. Optical Properties of the System Biliverdin‐Serum Albumin in Aqueous Medium

AbstractCircular dichroism (CD) and light‐absorption measurements in the wavelength range 300 to 650 nm were carried out for complexes of biliverdin (∼ 2.5 × 10−5 M) with either bovine or human serum albumin (charcoal treated) in aqueous solution (25–27°C) at several protein concentrations and pH values in the range 4 to 10. In all cases investigated, two large ellipticity bands were measured near 385 nm and about 650 nm, respectively, which were of opposite sign. In addition, two smaller bands near 300 and 535 nm were resolved by computer analysis into Gaussian curves of the CD spectrum of biliverdin‐human serum albumin complexes. The main CD bands were inverted in their sign in biliverdin‐bovine serum albumin complexes when compared at pH 5 and 10. Under the conditions used, free biliverdin did not show significant optical activity. The optical activity observed for the complexes is attributed to electric transition dipole coupling of biliverdin with protein transitions and to possible formation of skewed conformations of the biliverdin chromophore upon binding, leading to inherent dissymmetry. Unlike the corresponding bilirubin complexes investigated previously, there appears to be no evidence for substantial band splitting in the small molecule occurring upon binding to the biopolymer. Thus the presence of a center methene bridge instead of an isolating methylene group, the latter allowing internal rotation in the bile pigment, appears largely to determine the mechanism of generation of optical activity. In the case of bilirubin and at excess serum albumin, the observed optical activity is considered to be due mainly to exciton coupling between electric transition dipole moments of the dipyrromethene chromophores within the asymmetrically bound bilirubin. The optical properties investigated may serve as a very sensitive measure of the different types of interaction between the biopolymer and the small conjugated molecule which result from structural and conformational differences of the molecules participating in complex formation.