Conformation In Solid State Research Articles

Solid state and solution behaviour of N-(2-pyridyl)- and N-(4-methyl-2-pyridyl)aminomethane-1,1-diphosphonic acids

The crystal structures of N-(2-pyridyl)aminomethane-1,1-diphosphonic acid ( 1) and N-(4-methyl-2-pyridyl)aminomethane-1,1-diphosphonic acid ( 2) are determined and discussed with respect to their geometry and solid state organization. Compounds 1 and 2 crystallize as the opposite E and Z isomers. However, in solution both appear as a mixture of the Z and E forms. From the temperature dependence of NMR spectra, the Z/ E ratio is assigned to be nearly equal in 1 and 0.69:0.31, respectively, in 2. The role of a substituent position on the pyridyl ring for the Z/ E ratio in solution and for solid state conformations of N-(2-pyridyl)aminomethane-1,1-diphosphonic acids is discussed as well.

1-(1-Naphthylsulfonyl)-1a,2,6,6a-tetrahydro-1H,4H-1,3-dioxepino[5,6-b]azirine

The solid-state conformation of the title compound, C15H15NO4S, has been established by X-ray crystallography. The orientation of the sulfonyl moiety is defined by the C—S—N—C torsion angle of −108.24 (16)°. The angle between the naphthyl ring and the direction of the S—N bond is 71.24 (18)°. The dioxepinoaziridine moiety system a boat–chair (BC) conformation. The crystal packing is defined by optimized π–π inter­actions between parallel naphthyl groups.

Solid and solution state conformations of (±)-3- O-acetyl-1,2:4,5-di- O-isopropylidene- allo-inositol and (±)-3- O-acetyl-1,2:4,5-di- O-isopropylidene-6- O-methyl- allo-inositol

The synthesis and conformational studies of (±)-3- O-acetyl-1,2:4,5-di- O-isopropylidene- allo-inositol and (±)-3- O-acetyl-1,2:4,5-di- O-isopropylidene-6- O-methyl- allo-inositol are described. Solid state conformations of the title compounds have been studied by solving their X-ray crystal structures. The inositol ring in both the compounds deviate considerably from the ideal chair conformation to flattened chair conformation in the solid state. Their conformations in solution were studied by the use of 1H NMR spectroscopy. These conformational analyses revealed that the title compounds adopt similar conformations in solid and solution states irrespective of the solvent polarity.

Molecular structure and hydrolytic stability amidinium salts derived from triazatricyclo[5.2.1.0 4,10]decane

Five amidinium salts have been prepared from triazatricyclo[5.2.1.0 4,10]decane (tacnoa) and characterised by mass spectrometry, NMR spectroscopy and X-ray crystallography. The X-ray structures revealed a long distance between the methine carbon and the ammonium nitrogen, viz., C–N distance 1.64–1.70 Å, cf. other C–N distances of 1.40–1.50 Å. An NMR study of 1-ethyl-4,7-diaza-1-azoniatricyclo[5.2.1.0 4,10]decane and 1-benzyl-4,7-diaza-1-azoniatricyclo[5.2.1.0 4,10]decane, confirmed that these amidinium salts hydrolyse in aqueous solution, the latter 60 times faster than the former. Tacnoa, which has C–N distances typical of single bonds, showed no evidence of hydrolysis after several days at 80 °C. Molecular modeling calculations indicate that the preferred gas phase structure of the salts is one where the positive charge is delocalised over the two secondary amines and the methine carbon. The calculated distance between this carbon and the ammonium nitrogen is 0.15–0.4 Å longer than in the crystal structure. The energy difference between the preferred gas phase and solid state conformations is 2 kJ mol −1 and presents little barrier to nucleophilic attack of the methine carbon. Further analysis of the methine carbon geometry (C(7)) reveals that the bond angles in the benzyl salt are closer to those expected for an sp 2 centre than in the ethyl salt and that this could be the origin of the faster hydrolysis rate.

Fine tuning of folded conformation by change of substituents: 1H NMR and crystallographic evidence for folded conformation due to arene interactions in pyrazolo[3,4-d]pyrimidine core based ‘propylene linker’ compounds

Proton NMR and X-ray crystallographic analysis of two newly synthesized ‘trimethylene linker,’ (Leonard linker) compounds 1,3-bis(4-ethoxy-6-methylsulfanyl-lH-pyrazolo[3,4-d]pyrimidin-1-yl)propane (4c) and 1,3-bis(4-isopropoxy-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)propane (4d) show intramolecularly stacked conformations both in solution and solid state. Robustness of the unusual U-motif formed due to intramolecular stacking in earlier related compounds (1, n=3 and 3, n=3) is not only confirmed but additional fine tuning is also achieved in new compounds (4) formed by replacement of remote 4-alkylsulfanyl group in 1a by 4-alkoxy substituents.

Synthesis and Solid-State Conformation of a Calix[8]arene 1,5-Diquinone Derivative

The first example of a calix[8]quinone derivative, hexamethoxy-p-tert-butylcalix[8]-1,5-diquinone 5, has been synthesized from p-tert-butylcalix[8]arene 1by exploiting a protection-deprotection procedure. The structure of the 5·toluene inclusion compound has been determined by a single crystal X-ray diffraction study. The calix[8]arene molecule possesses a crystallographic inversion centre and assumes a ‘pseudo-chair-like’ conformation, with two opposite 3/4-cone moieties, which resembles the previously reported chair-like conformation of p-tert-butylcalix[8]arene. The 4 toluene molecules per unit cell occupy interstitial voids and are released in the temperature range of 30–160 °C.

2-Acetamido-N-benzyl-1,4-imino-1,2,4-trideoxy-L-arabinitol 0.33-hydrate

The solid-state conformation of the title compound, C14H20N2O3·0.33H2O, a potent hexosaminidase inhibitor, prepared from d-lyxonolactone, has been established by X-ray crystallography. The asymmetric unit contains three mol­ecules, which have very similar conformations, together with a mol­ecule of water.

Synthesis of Cyclohexapeptides Containing Pro and Aib Residues.

Cyclization reactions on hexapeptides containing several alpha-aminoisobutyric acid (= 2-amino-2-methylpropanoic acid; Aib) residues and the turn-promoting glycine (Gly) and proline (Pro) residues were investigated. Eight linear hexapeptides were synthesized, and their cyclization was attempted with various coupling reagents. The macrolactamization step proved to be difficult since only three hexapeptides could be cyclized. Two of these latter peptides were the linear precursors of the same cyclic hexapeptide, cyclo(Aib-Aib-Phe-Pro-Aib-Gly) (1). Surprisingly, they gave 1 in almost the same yield. Thus, 1 was obtained in 35% yield upon ring closure at the Phe/Pro site by using DEPBT as the coupling reagent, whereas the cyclization at the Aib/Phe site led to 1 in 28 and 34% yield by using PyAOP and DEPC, respectively (DEPBT = 3-[(diethoxyphosphoryl)oxy]-1,2,3-benzotriazin-4(3H)-one, PyAOP = (1H-7-azabenzotriazol-1-yloxy)tripyrroli- din-1-ylphosphonium hexafluorophosphate, DEPC = diethyl phosphorocyanidate). Another cyclic hexapeptide, cyclo(Aib-Aib-Gly-Aib-Pro-Gly) (2) was prepared in 34% yield when DEPC was used in the cyclization step. The solid-state conformation of 1 was established by X-ray crystallography.

Solid state conformational classification of eight-membered rings in copper complexes double bridged by phosphate, phosphonate or phosphinate ligands

A statistical classification of the solid state conformation in the title complexes using data retrieved from the Cambridge Structural Database (CSD) has been made. Phosphate and phosphinate complexes show a chair conformation preferably. In phosphonate complexes, the most frequent conformations are found to be boat– chair, chair and boat– boat; in all the boat– chair cases, the phosphorus atoms appear connected by a bridging carbon atom.

Synthesis and conformational analysis of 18-membered Aib-containing cyclohexapeptides

The synthesis and conformational analysis of two Aib-containing cyclic hexapeptides, cyclo(Gly-Aib-Leu-Aib-Phe-Aib) 1 and cyclo(Leu-Aib-Phe-Gly-Aib-Aib) 2 , is described. The linear precursors of 1 and 2 were prepared using solution phase techniques, and the cyclization efficiency of three different coupling reagents (HATU, PyAOP, DEPC) was examined. The success of the cyclization was found to be reagent dependent. Solid-state conformational analysis of 1 and 2 was performed by X-ray crystallography and has revealed some unusual features as all three Aib residues of 1 assume nonhelical conformations. Furthermore, the residue Aib 4 adopts an extended conformation ( ϕ=−175.9(3)°, ψ=+178.6(2)°), which is, to the best of our knowledge, the first observation of an Aib residue adopting an extended conformation in a cyclopeptide. The structure of 1 is also a rare example in which an Aib residue occupies the ( i+1) position of a type II′ β-turn, stabilized by a bifurcated hydrogen bond. The cyclic peptide 2 adopts a more regular conformation in the solid state, consisting of two fused β-turns of type I/I′, stabilized by a pair of intramolecular hydrogen bonds. In addition, the conformational study of the cyclic peptide 1 in DMSO- d 6 by NMR spectroscopy and molecular dynamics simulations revealed a structure, which is very similar to its structure in the crystalline state.

On the solid state conformation of azithromycin monohydrate and dihydrate pseudopolymorphs

Abstract This paper describes the crystal structure of the azithromycin monohydrate pseudopolymorph (pseudopolymorphic forms, different solvates of the same chemical compound, azithromycin in our case) crystallised from isopropanol, solved by X-ray single crystal, and called isopropanol clathrate monohydrate (Apotex, US 6,245,903). The powder diffraction patterns for this compound show a structure very similar to the azithromycin monohydrate crystallised from ethanol, called stable monohydrate (Biochemie, WO 0100640), and the X-ray single crystal confirms the fact that this new pseudopolymorph is isostructural to the previously reported, the referred stable monohydrate. Comparing the monohydrate and the dihydrate crystalline forms, we try to explain the role played by the solvent in the final results, and find a relation between the conformation in solution and in the crystal state conformation for the antibiotic. The crystal obtained using t-butanol as solvent, differs from the expected and certainly more factors have to be considered in addition to the solvent polarity (dipole moment μ) to determine the final crystal form of azithromycin, contrary to that indicated in the literature. The concept of polarity itself is analyzed.

An extensive study of bromination of cis,trans,trans-1,5,9-cyclododecatriene: product structures and conformations

Bromine has been added to cis,trans,trans-1,5,9-cyclododecatriene under various reaction conditions. All expected direct addition products have been isolated, and their structures have been determined by microanalysis, NMR and X-ray crystallography. Advanced NMR techniques were used to determine solution conformations of several of the compounds, enabling comparison with the solid-state conformations obtained by crystallography.

Solid state conformations of symmetrical aromatic biheterocycles: an X-ray crystallographic investigation

Accurate, low temperature X-ray crystal structure determinations show that 3,3'-biquinoline (6), 2,2'-biquinazoline (7), 2,2'-biquinoxaline (8), 2,2'-bibenzoxazole (10) and 2,2'-bibenzothiazole (11) all exist in the solid state in centrosymmetric, planar conformations that minimise their dipole moments and maximise both conjugation between the rings and various types of attractive intermolecular associations. In contrast, 4,4'-biquinazoline (9) and 1,1'-bibenzotriazole (12) display non-planar conformations due to repulsive intramolecular interactions.

Synthesis of Cyclohexapeptides Containing Pro and Aib Residues

AbstractCyclization reactions on hexapeptides containing several α‐aminoisobutyric acid (=2‐amino‐2‐methylpropanoic acid; Aib) residues and the turn‐promoting glycine (Gly) and proline (Pro) residues were investigated. Eight linear hexapeptides were synthesized, and their cyclization was attempted with various coupling reagents. The macrolactamization step proved to be difficult since only three hexapeptides could be cyclized. Two of these latter peptides were the linear precursors of the same cyclic hexapeptide, cyclo(Aib‐Aib‐Phe‐Pro‐Aib‐Gly) (1). Surprisingly, they gave 1 in almost the same yield. Thus, 1 was obtained in 35% yield upon ring closure at the Phe/Pro site by using DEPBT as the coupling reagent, whereas the cyclization at the Aib/Phe site led to 1 in 28 and 34% yield by using PyAOP and DEPC, respectively (DEPBT=3‐[(diethoxyphosphoryl)oxy]‐1,2,3‐benzotriazin‐4(3H)‐one, PyAOP=(1H‐7‐azabenzotriazol‐1‐yloxy)tripyrrolidin‐1‐ylphosphonium hexafluorophosphate, DEPC=diethyl phosphorocyanidate). Another cyclic hexapeptide, cyclo(Aib‐Aib‐Gly‐Aib‐Pro‐Gly) (2) was prepared in 34% yield when DEPC was used in the cyclization step. The solid‐state conformation of 1 was established by X‐ray crystallography.

Solution‐Phase Synthesis of Aib‐Containing Cyclic Hexapeptides

The 18-membered Aib-containing cyclohexapeptides, cyclo(-Gly-Aib-Aib-Gly-Aib-Phe-) (22), cyclo(-Gly-Aib-Phe(2Me)-Gly-Aib-Aib-) (24a), cyclo(-Gly-Phe(2Me)-Aib-Gly-Aib-Aib-) (24b), and cyclo(-Gly-Phe(2Me)-Aib-Gly-Aib-Phe-) (25), have efficiently been synthesized by solution-phase techniques. The linear precursors 1a-1d were prepared by combining the 'azirine/oxazolone method' for incorporation of alpha,alpha-disubstituted alpha-amino acids (Aib, Phe(2Me)) into the peptide chains by classical peptide coupling methods for segment condensations. Deprotection of the amino and carboxy termini of 1a-1d, followed by cyclization with DEPC as the coupling reagent, gave the above-mentioned cyclic hexapeptides 22, 24a, 24b, and 25 in good yields (26-57%). The solid-state conformations of the linear hexapeptides 1d, 16 and 27, and of the cyclohexapeptides 22 and 25 have been established by X-ray crystallography.

Binding of the Oxo−Rhenium(V) Core to Methionine and to N-Terminal Histidine Dipeptides

The ReOX(2)(met) compounds (X = Cl, Br) adopt a distorted octahedral structure in which a carboxylato oxygen lies trans to the Re=O bond, whereas the equatorial plane is occupied by two cis halides, an NH(2), and an SCH(3) group. Coordination of the SCH(3) unit creates an asymmetric center, leading to two diastereoisomers. X-ray diffraction studies reveal that the crystals of ReOBr(2)(d,l-met).1/2H(2)O and ReOBr(2)(d,l-met).1/2CH(3)OH contain only the syn isomer (S-CH(3) bond on the side of the Re=O bond), whereas ReOCl(2)(d-met) and ReOCl(2)(d,l-met) consist of the pure anti isomer. (1)H NMR spectroscopy shows that both isomers coexist in equilibrium in acetone (anti/syn ratio = 1:1 for X = Br, 3:1 for X = Cl). Exchange between these two isomers is fast above room temperature, but it slows down below 0 degrees C, and the sharp second-order spectra of both isomers at -20 degrees C were fully assigned. The coupling constants are consistent with the solid-state conformations being retained in solution. Complexes of the type [ReOX(2)(His-aa)]X (X = Cl, Br) are isolated with the dipeptides His-aa (aa = Gly, Ala, Leu, and Phe). X-ray diffraction work on [ReOBr(2)(His-Ala)]Br reveals the presence of distorted octahedral cations containing the Re=O(3+) core and a dipeptide coordinated through the histidine residue via the imidazole nitrogen, the terminal amino group, and the amide oxygen, the site trans to the Re=O bond being occupied by the oxygen. The alanine residue is ended by a protonated carboxylic group that does not participate in the coordination. The constant pattern of the(1)H NMR signals for the protons in the histidine residue confirms that the various dipeptides adopt a similar binding mode, consistent with the solid-state structure being retained in CD(3)OD solution.

Synthesis and Characterization of Zirconium and Iron Complexes Containing Substituted Indenyl Ligands: Evaluation of Steric and Electronic Parameters

Evaluation of the steric and electronic influence of a family of silyl- and alkyl-substituted indenyl ligands on zirconium and iron centers has been accomplished by a combination of X-ray diffraction, IR spectroscopy, solution NMR dynamics, and electrochemical measurements. Three tetrasubstituted, bis-indenyl zirconocene dichloride complexes have been characterized by X-ray diffraction and adopt a gauche ligand conformation such that the interactions between tertiary substituents on adjacent rings are minimized. Similar solid state conformations were also observed in two of the corresponding iron compounds. Evaluation of the electronic environment about each zirconium center was achieved by measurement of the CO stretching frequencies of the dicarbonyl derivatives. Simple inductive effects govern the electronic properties of each zirconocene where silyl groups are relatively electron withdrawing and alkyl groups electron donating. For the most hindered zirconocene dicarbonyl derivatives, population of thr...

Conformational analysis: crystallographic, molecular mechanics and quantum chemical studies of C--H...O hydrogen bonding in the flexible bis(nosylate) derivative of catechol.

The single-crystal X-ray diffraction analysis of 2-[[(4-nitrophenoxy)sulfonyl]oxy]phenyl 4-nitrophenyl sulfate (4) reveals that an interesting intermolecular or extended structure (a one-dimensional hydrogen-bonded polymer) is formed because of pairs of intermolecular (aryl)C--H...O(nitro) hydrogen bonds between the C(2) symmetry monomer units. The axis of the hydrogen-bonded polymer runs co-linear with the [101] face diagonal of the monoclinic unit cell. Molecular mechanics calculations using a modified version of the MM+ force field and a random conformational search algorithm have been used to locate the important low-energy in vacuo conformations of (4). The MM-calculated conformation of (4) that most closely matches the X-ray structure lies some 26.5 kJ mol(-1) higher in energy than the global minimum-energy conformation, consistent with the notion that the crystallographically observed molecular architecture of (4) is a local energy minimum in the absence of its crystal lattice environment. Since the X-ray conformation of (4) was correctly calculated only when all of the neighbouring molecules in the crystal lattice were included in the simulation, hydrogen bonding and other non-bonded interactions in the crystal lattice clearly dictate the experimentally observed conformation of (4). Quantum chemical calculations (AM1 method) confirm the critical role played by the intermolecular (aryl)C--H...O(nitro) hydrogen bonds in controlling the crystallographically observed conformation of (4) and show that self-recognition in this system by hydrogen bonding is favoured on electrostatic grounds. Collectively, the molecular simulations suggest that because the lowest-energy molecular conformation of (4) does not permit the formation of an extended hydrogen-bonded 'supramolecular' structure, it is not the preferred conformation in the crystalline solid state.

Hydrogen-Bonding-Induced Planar, Rigid, and Zigzag Oligoanthranilamides. Synthesis, Characterization, and Self-Assembly of a Metallocyclophane

Four oligoanthranilamides 1-4, which are incorporated with three, five, seven, or nine benzene units, respectively, have been synthesized and characterized. X-ray analysis, 1D and 2D (1)H NMR, and IR experiments reveal that all the new oligoamides adopt rigid, planar and zigzagged conformations in both solution and solid state, which are stabilized by intramolecular three-center hydrogen bonding. A 5-mer oligomer 22, which is incorporated with two acetylene groups at the ends, has also been synthesized and utilized for the self-assembly of a rigid hydrogen-bonded metallocyclophane. The new rigid oligoanthranilamides represent useful building blocks for the construction of supramolecular architectures.

Ortho-Tetraaryls as helical building blocks: a study of structure, theory, electrochemistry, and optical properties

( ortho)-3,3′-Diphenyl-2,2′-bithiophene is shown to exhibit a solid-state helical conformation that is consistent with MMFF predictions of structure. The optical, electronic, and conformational properties of this compound are examined, and the results are commensurate with a helical building block capable of exhibiting redox-induced conformational changes along the long molecular axis. Such a property demonstrates promise for this tetramer to function as building block for a spring-like electromechanical actuator.