Conformation In Solid State Research Articles

6,7-Bismethoxy-2,11-dihydroxytetraphenylene Derived Macrocycles: Synthesis, Structures, and Complexation with Fullerenes.

6,7-Bismethoxy-2,11-dihydroxytetraphenylene (1), a novel building block of tetraphenylene-derived macrocycles, was synthesized via palladium-catalyzed cross-coupling reactions and characterized by X-ray diffraction. The relevant macrocyclic hosts derived from 1 have well-defined structures with fixed conformations both in solution and solid state. They showed efficient and unique properties toward complexation with fullerenes C60 and C70 in toluene.

Water-Soluble Copolypeptides with Oligo-Ethylene-Glycol and Benzyl Pendants: Synthesis, Characterization, and Thermoresponsive Properties

A series of random copolypeptides, i.e. poly(γ-propyl-l-glutamate)-graft-(oligo-ethylene-glycol)-random-poly(γ-benzyl-l-glutamate)s (PPLG-g-OEG3-ran-PBLG) with similar main chain lengths and various compositions of OEG and benzyl pendants were synthesized in three steps, including ring-opening polymerization of γ-chloropropyl-l-glutamic acid-based N-carboxyanhydride (CPLG-NCA) and γ-benzyl-l-glutamic acid-based N-carboxyanhydride (BLG-NCA), nucleophilic substitution in the presence of NaN3, and copper-mediated alkyne–azide 1,3-dipolar cycloaddition. 1H NMR, Fourier transform infrared spectroscopy, and gel permeation chromatography results confirmed the molecular structures of the resulting copolypeptides and characterized their molar masses, molar mass distributions, and the OEG/benzyl compositions. Fourier transform infrared spectroscopy and circular dichroism analysis revealed that PPLG-g-OEG3-ran-PBLG samples adopted α-helical conformations both in aqueous solution and solid state. Variable-temperature UV-visible spectroscopy revealed that PPLG-g-OEG3-ran-PBLG samples with high OEG molar content (x ≥ 0.57) possessed lower critical solution temperature-type phase transitions in water. The cloud point temperature, in the range of 22–53°C, can be readily obtained by controlling the OEG/benzyl composition.

Rubrene: The Interplay between Intramolecular and Intermolecular Interactions Determines the Planarization of Its Tetracene Core in the Solid State.

Rubrene is one of the most studied molecular semiconductors; its chemical structure consists of a tetracene backbone with four phenyl rings appended to the two central fused rings. Derivatization of these phenyl rings can lead to two very different solid-state molecular conformations and packings: One in which the tetracene core is planar and there exists substantive overlap among neighboring π-conjugated backbones; and another where the tetracene core is twisted and the overlap of neighboring π-conjugated backbones is completely disrupted. State-of-the-art electronic structure calculations show for all isolated rubrene derivatives that the twisted conformation is more favorable (by -1.7 to -4.1 kcal mol(-1)), which is a consequence of energetically unfavorable exchange-repulsion interactions among the phenyl side groups. Calculations based on available crystallographic structures reveal that planar conformations of the tetracene core in the solid state result from intermolecular interactions that can be tuned through well-chosen functionalization of the phenyl side groups and lead to improved intermolecular electronic couplings. Understanding the interplay of these intramolecular and intermolecular interactions provides insight into how to chemically modify rubrene and similar molecular semiconductors to improve the intrinsic materials electronic properties.

Indachlorins: nonplanar indanone-annulated chlorin analogues with panchromatic absorption spectra between 300 and 900 nm.

Indaphyrins, pyrrole-modified porphyrins containing a cleaved pyrrole β,β'-bond and two annulated indanone moieties, possess unusually broadened and redshifted UV/Vis spectra because of their π-expanded chromophores. The parent free base indaphyrin has been crystallographically characterized, highlighting its strongly ruffled conformation incorporating a helimeric twist. It was shown to be susceptible to regiospecific derivatizations at the opposite side of the ring-cleaved pyrrole (dihydroxylation, followed by functional group transformations of the resulting diol functionality), generating indaphyrin-based chlorin analogues, indachlorins, that incorporate a dihydroxypyrroline, pyrrolindione, oxazolone, or a morpholine moiety. Structural modifications resulted in further broadening and hyper- and bathochromic shifts of the optical spectra, some of which possess a nearly panchromatic absorption between 300 to well above 900 nm. The extents to which these modifications affect their solid-state conformations were analyzed.

Synthesis and secondary conformations of homochiral β-oligopeptides containing aryl side chains

A series of novel homochiral α-oligopeptides bearing aryl side chains was designed and synthesized from (S)-α-phenyl-α-amino acid derivatives by solution-phase methods. By means of circular dichroism(CD), Fouriertransform infrared spectrometry(FTIR), powder X-ray diffraction analysis(XRD) and density functional theory(DFT) calculations, we suggest that dipeptide P-2 and tripeptide P-3 adopt random coil-like conformations, pentapeptide P-5 and hexapeptide P-6 adopt stable 12-helix conformations in both solution and solid-state. Meanwhile, tetrapeptide P-4 adopt random coil-like conformation in solution and adopt 12-helix conformation in solid state.

Uranyl(VI) binding by bis(2-hydroxyaryl)diimine and bis(2-hydroxyaryl)diamine ligand derivatives. Synthetic, X-ray, DFT and solvent extraction studies

The interaction of uranyl(VI) nitrate with a series of bis(2-hydroxyaryl)imine (H2L1–H2L5) and bis(2-hydroxyaryl)amine (H2L8, H2L9) derivatives incorporating 1,3-dimethylenebenzene or 1,3-dimethylenecyclohexane bridges between nitrogen sites is reported. Crystalline complexes of type [UO2(H2L)(NO3)2] (where H2L is H2L1–H2L4) were isolated from methanol. X-ray structures of the complexes of H2L1, H2L2 and H2L4 show that each of these neutral ligands bind to their respective UO22+ centres in a bidentate fashion in which coordination only occurs via each ligand’s hydroxy functions. Two bidentate nitrate anions complete the metal’s coordination sphere in each complex to yield hexagonal bipyramidal coordination geometries. A density functional theory (DFT) investigation of [UO2(H2L1)(NO3)2] in a simulated methanol environment is in accord with this complex maintaining its solid state conformation in solution. Solvent extraction experiments (water/chloroform) employing H2L1–H2L7 in the organic phase and uranyl(VI) nitrate in the aqueous phase showed that both amine derivatives, H2L8 and H2L9, yielded enhanced extraction of UO22+ over the corresponding imine derivatives, H2L1 and H2L2. These results were further compared with those obtained for the corresponding Schiff bases incorporating 1,2-phenylene and 1,2-cyclohexane bridged ligands, H2L6 and H2L7; these more rigid systems also yielded enhanced extraction of UO22+ relative to the more flexible Schiff bases H2L1–H2L5. A very significant synergistic enhancement of the extraction of UO22+ by H2L1–H2L4 and H2L7 was observed in the presence of a 10-fold excess of n-octanoic acid; the influence of pH on extraction efficiency was also investigated. A parallel set of experiments employing H2L1–H2L9 as extractants for europium(III) nitrate indicated a clear uptake preference for UO22+ over Eu3+ in all cases; separation of the uranyl ion from the rare earths is an important objective in mineral processing.

Receptor-bound conformation of cilengitide better represented by its solution-state structure than the solid-state structure.

The X-ray crystal and NMR spectroscopic structures of the peptide drug candidate Cilengitide (cyclo(RGDf(NMe)Val)) in various solvents are obtained and compared in addition to the integrin receptor bound conformation. The NMR-based solution structures exhibit conformations closely resembling the X-ray structure of Cilengitide bound to the head group of integrin αvβ3. In contrast, the structure of pure Cilengitide recrystallized from methanol reveals a different conformation controlled by the lattice forces of the crystal packing. Molecular modeling studies of the various ligand structures docked to the αvβ3 integrin revealed that utilization of the solid-state conformation of Cilengitide leads-unlike the solution-based structures-to a mismatch of the ligand-receptor interactions compared with the experimentally determined structure of the protein-ligand complex. Such discrepancies between solution and crystal conformations of ligands can be misleading during the structure-based lead optimization process and should thus be taken carefully into account in ligand orientated drug design.

Quinoxaline-walled π-stacking molecules: synthesis, conformation, and luminescence properties

A series of semi-rigid N-phenylsuccinimides I (11Xy), N-arylmethylsuccinimides II (18Xy), and N,N′-(1,4-arylenebis(methylene))disuccinimides III (19XyX) walled by quinoxaline (QX), dimethylquinoxaline (diMQX), or benzoquinoxaline (BQX) ring were synthesized. Intramolecular π–π interactions in solution were detected by NMR and fluorescence spectroscopy, in terms of reciprocal anisotropic shielding and exciplex formation, respectively. The X-ray crystallographic analysis revealed the preferential conformations in solid state, which were compatible with the results of conformational studies by NMR and fluorescence spectroscopy. The results collectively indicated that 18Xy and 19XyX are driven by intramolecular π–π interactions in the mode of π-stacking (face-to-face) or T-shaped (edge-to-face) configuration to preferentially adopt the folded- and the double folded-conformation, respectively, where the spaced aromatic rings are oriented syn to each other in close proximity.

Palladium(II) complexes supported by a bidentate bis(secondary)phosphine linked by pyridine

A series of complexes of the type (PNP-H2)PdX2 (X=Cl, Br, I) have been synthesized, where PNP-H2 is a bis(secondary)phosphine ligand linked by a pyridine, 2,6-(2′-(Ph(H)P)(C6H4))2(C5H3N). Due to chirality at phosphorus, the parent ligand exists as a mixture of nearly equivalent rac and meso diastereomers non-interconverting at room temperature. When ligated to Pd(II) halides, however, the diastereomeric ratio is dependent upon the halide. The chloro, bromo, and iodo complexes have been characterized crystallographically. Conformationally similar meso diastereomers of each dihalide are roughly Cs symmetric in the solid state, while the rac diastereomers (identified only for X=Br, I) show substantially different solid-state conformations.

Ligand hierarchy on driving the crystal packing. Effect of supramolecular interactions on solid-state conformations adopted by saccharinate Pd(ii) complexes

The potential of saccharinate as a supramolecular organizer in selected palladium complexes has been thoroughly evaluated from the perspective of those relevant interactions operating in organic salts and co-crystals in which saccharinate is involved. With this purpose, molecular and supramolecular structures of a series of bis-saccharinate complexes with the general formula trans-[Pd(sac)2(L)2] [L = pyridine (1), pyridazine (2), PPh3 (3), SMe2 (4) or nicotinamide (6)] containing co-ligands with different polarities and abilities to form intermolecular bonds have been studied by X-ray diffraction. These X-ray diffraction data were either previously reported (1 and 3), or obtained from newly determined crystal structures (2, 4 and 6). The new crystal structures of closely related complexes [Pd(sac)2(SMe2)(OH2)]·dmso (5) and [Pd(succinimide)2(nicot)2] (7) have also been elucidated and provide an additional structural discussion. We have disclosed that the anti-configuration is preferred for saccharinate ligands and that the CO group defines the most important supramolecular interactions in the crystal packing of 1, 2 and 4. The saccharinate ligand drives crystal packing when pyridine (1), pyridazine (2), PPh3 (3), or SMe2 (4) are the co-ligands, but the crystal packing orienting role relies on water (5) or nicotinamide (6 and 7) when these ligands are present. These results have been compared with other previously reported examples. Molecular geometries have been optimized by DFT, with the interesting output of the energetic preference by the syn-configuration. Supramolecular interactions distort conformations from those optimized ones so that complexes with stronger interacting ligands display larger distortions.

Strength from weakness: conformational divergence between solid and solution states of substituted cyclitols facilitated by CH···O hydrogen bonding.

We have investigated the conformational preferences of a series of cyclitol derivatives, namely mono- and diesters of 1,2:5,6-di-O-isopropylidene-myo-inositol and 1,2:5,6-di-O-cyclohexylidene-myo-inositol, in both solid and solution states. The solid-state conformations were determined by single-crystal X-ray analysis. The solution-state conformations were determined by using NMR. The experimental (3)J(HH) values were applied in the Haasnoot-Altona equation to calculate the dihedral angle (ϕ) between the respective vicinal protons. By fixing the dihedral angle between different sets of vicinal protons, the molecules were energy-minimized by MM2 method to visualize their conformation in solution. As the solvent polarities can influence the conformational preference, we have determined the conformations of these molecules in various solvents of different polarities such as benzene-d6, chloroform-d, acetonitrile-d3, acetone-d6, methanol-d4, and DMSO-d6. All of the compounds adopted boat conformations in solution irrespective of the solvents, acyl groups, or alkylidene protecting groups. This conformation places H6 and O3 of the cyclitol ring in proximity, such that an intramolecular CH···O hydrogen bond between them stabilizes this otherwise unstable conformation. However, in the solid state, several intermolecular CH···O hydrogen bonds force these molecules to adopt the chair conformation. This study uncovers the role of weak noncovalent interactions in influencing the molecular conformations differentially in different states.

Simultaneous use of solution NMR and X-ray data in REFMAC5 for joint refinement/detection of structural differences.

The program REFMAC5 from CCP4 was modified to allow the simultaneous use of X-ray crystallographic data and paramagnetic NMR data (pseudocontact shifts and self-orientation residual dipolar couplings) and/or diamagnetic residual dipolar couplings. Incorporation of these long-range NMR restraints in REFMAC5 can reveal differences between solid-state and solution conformations of molecules or, in their absence, can be used together with X-ray crystallographic data for structural refinement. Since NMR and X-ray data are complementary, when a single structure is consistent with both sets of data and still maintains reasonably `ideal' geometries, the reliability of the derived atomic model is expected to increase. The program was tested on five different proteins: the catalytic domain of matrix metalloproteinase 1, GB3, ubiquitin, free calmodulin and calmodulin complexed with a peptide. In some cases the joint refinement produced a single model consistent with both sets of observations, while in other cases it indicated, outside the experimental uncertainty, the presence of different protein conformations in solution and in the solid state.

“Conformation Locked” Strong Electron-Deficient Poly(p-Phenylene Vinylene) Derivatives for Ambient-Stable n-Type Field-Effect Transistors: Synthesis, Properties, and Effects of Fluorine Substitution Position

The charge carrier mobility of p-type and ambipolar polymer field-effect transistors (FETs) has been improved substantially. Nonetheless, high-mobility n-type polymers are rare, and few can be operated under ambient conditions. This situation is mainly caused by the scarcity of strong electron-deficient building blocks. Herein, we present two novel electron-deficient building blocks, FBDOPV-1 and FBDOPV-2, with low LUMO levels down to -4.38 eV. On the basis of both building blocks, we develop two poly(p-phenylene vinylene) derivatives (PPVs), FBDPPV-1 and FBDPPV-2, for high-performance n-type polymer FETs. The introduction of the fluorine atoms effectively lowers the LUMO levels of both polymers, leading to LUMO levels as low as -4.30 eV. Fluorination endows both polymers with not only lower LUMO levels, but also more ordered thin-film packing, smaller π-π stacking distance, stronger interchain interaction and locked conformation of polymer backbones. All these factors provide FBDPPV-1 with high electron mobilities up to 1.70 cm(2) V(-1) s(-1) and good stability under ambient conditions. Furthermore, when polymers have different fluorination positions, their backbone conformations in solid state differ, eventually leading to different device performance.

Conformation differences in N-[2-(1-arenesulfonyl-1H-pyrazol-3-yl)-6-methyl-phenyl]-arenesulfon­amides, (arene = benzene and 4-toluene)

Abstract The crystal structures are reported of N-[2-(1-benzenesulfonyl-1H-pyrazol-3-yl)-6-methyl-phenyl]-benzenesulfonamide, 1, and N-[2-(1-toluene-4-sulfonyl-1H-pyrazol-3-yl)-6-methyl-phenyl]-benzenesulfonamide, 2: two compounds used in a recently reported antileishmania study. The crystallographic study reveals significant differences in the conformations adopted by molecules of 1 compared to those adopted by the three independent molecules of 2 in the solid state. The conformation differences between molecules of 1, on one hand, and the three molecules of 2, on the other, are not driven by steric effects within the molecular arrangements. If molecules 2 adopted the molecular conformation found for 1, severe steric interference would occur in the chains and other aggregates generated from the intermolecular contacts. As all the intermolecular interactions are of a weak nature, it is unlikely that aggregation would survive in dilute aqueous media, and hence the steric constraints on the conformations adopted in the solid state would not be in place in solution. Thus the difference in the solid state conformations offers no light on the greater activity of compound 1 compared to that of compound 2 in the antileishmania study in aqueous media.

Synthesis and Properties of Branched Oligo(2-thienyl)- and Oligo(2,2′-bithien-5-yl)-Substituted Pyridine Derivatives

Starting from easily accessible precursors we describe the preparation of a series of branched oligo(2-thienyl)- and oligo(2,2′-bithienyl)-substituted pyridine derivatives. With palladium-catalyzed cross-coupling reactions of pyridyl nonaflates/triflates as key steps we synthesized 2,6-di(2-thienyl)pyridines bridged by thiophene or benzene rings. By selective bromination of 2,6-di(2-thienyl)pyridine and 2,4,6-tri(2-thienyl)pyridine and subsequent coupling reactions an access to oligo(2,2′-bithien-5-yl)-substituted pyridine derivatives was gained. The constitution and solid state conformation of 2,6-bis(2,2’-bithien-5-yl)pyridine was determined by X-ray analysis. This series of new pyridine-thiophene conjugates was systematically investigated by UV/vis spectroscopy. Large Stokes shifts in the neutral and protonated form were observed. The electrochemical oxidation of two typical compounds was studied, however, these oxidations were irreversible forming a polymeric film at the anode. As a selected example, a thiophene-bridged 2,6-di(2-thienyl)pyridine derivative was also investigated by scanning tunneling microscopy showing an interesting self-assembly into a highly ordered monolayer on highly oriented pyrolytic graphite.

One‐Pot Multi‐Component Synthesis and Solid State Structures of Functionally Rich Polyether Macrocycles

AbstractDensely functionalized polyether macrocycles can be prepared in one pot in yields up to 60% by the rhodium(II)‐catalyzed decomposition of methyl diazoacetoacetate in the presence of a variety of substituted or unsaturated 5‐ and 6‐membered ring cyclic ethers. A comprehensive analysis of the solid state conformations of the macrocyclic geometries is detailed as well as novel mechanistic insights about the multi‐component condensation reaction.magnified image

How metallation affects solid-state conformation and assembly of hexameric cyclic peptoids

How metallation affects solid-state conformation and assembly of hexameric cyclic peptoids

Conformational study of the structure of 18-thiacrown-6

Conformational analysis was performed for 18-thiacrown-6 (18t6) using the CONFLEX method and the MMFF94s force field. Computations were performed for some of the low energy conformations at the HF, B3LYP, CAM-B3LYP, M06, M06L, M062x, M06HF and MP2 levels. The computations were also performed using the DFT-D3 method along with the TPSS and PBE functionals. The study predicted a new C2 conformation as the ground state conformation of 18t6. This new C2 conformation is more stable than the experimentally known solid state conformation by 4.7kcal/mol at the MP2/6-311G** level. This conformation has all of the SCCS dihedral angles adopt exodentate structure. However, the experimentally known conformation of the solid phase has two of the SCCS dihedral angles violating this exodentate rule. It was concluded that for 18t6 stability a linear dihedral SCCS angle requirement is more important than a gauche CSCC dihedral angle requirement.

An Experimental and Theoretical Conformational Study of a Series of Substituted 3-cyclohexyl-2-phenyl-1,3-thiazolidin-4-ones

A series of novel 3-cyclohexyl-2-phenyl-1,3-thiazolidin-4-one derivatives with substituents on the 2-phenyl ring were synthesized, and a study of their solid state and solution conformations was effected. In solution the thiazolidin-4-one ring preferred the C2 phenyl in a pseudo-equatorial orientation and the solid state indicated a preference for the C2 phenyl being in a pseudo-axial orientation. Less robust substituent chemical shift (SCS) correlations utilizing 13C NMR were observed in this instance than in prior studies. Molecular modeling studies using Moller-Plessett second-order perturbation theory (MP2) indicate that the thiazolidinone ring and cyclohexyl ring conformations exhibit a global minimum consistent with the solution studies.

Structures in solid state and solution of dimethoxy curcuminoids: regioselective bromination and chlorination

BackgroundSeveral papers described the structure of curcumin and some other derivatives in solid and in solution. In the crystal structure of curcumin, the enol H atom is located symmetrically between both oxygen atoms of the enolone fragment with an O···O distance of 2.455 Å, which is characteristic for symmetrical H-bonds. In the solution, the geometry of the enolone fragment is attributed to the inherent disorder of the local environment, which solvates one of the basic sites better than the other, stabilizing one tautomer over the other. In this paper, how the position of methoxy groups in dimethoxy curcuminoids influence the conformation of molecules and how the halogen atoms change it when they are bonded at α-position in keto-enol part of molecules is described.ResultsSix isomers of dimethoxy curcuminoids were prepared. Conformations in solid state, which were determined by X-ray single crystallography and 1H MAS and 13C CPMAS NMR measurements, depend on the position of methoxy groups in curcuminoid molecules. In solution, a fast equilibrium between both keto-enol forms exists. A theoretical calculation finding shows that the position of methoxy groups changes the energy of HOMO and LUMO. An efficient protocol for the highly regioselective bromination and chlorination leading to α-halogenated product has been developed. All α-halogenated compounds are present mainly in cis keto-enol form.ConclusionsThe structures in solid state of dimethoxy curcuminoids depend on the position of methoxy groups. The NMR data of crystalline solid samples of 3,4-diOCH3 derivative, XRD measurements and X-ray structures lead us to the conclusion that polymorphism exists in solids. The same conclusion can be done for 3,5-diOCH3 derivative. In solution, dimethoxy curcuminoids are present in the forms that can be described as the coexistence of two equivalent tautomers being in fast equilibrium. The position of methoxy groups has a small influence on the enolic hydrogen bond. Theoretical calculations show that the energy gap between HOMO and LUMO depend on the position of methoxy groups and are lower in solution. Chlorination and bromination on α-position of 1,3-diketone moiety do not change the preferential form being cis keto-enol as in parent compounds.