Investigation of structure and dynamics in a photochromic molecular crystal by NMR crystallography

A photochromic anil, N-(3,5-di-t-butylsalicylidene)-4-amino-pyridine, has been studied by single-crystal X-ray diffraction, multinuclear magic-angle spinning NMR, and first-principles density functional theory (DFT) calculations. Interpretation of the solid-state NMR data on the basis of calculated chemical shifts confirms the structure is primarily composed of molecules in the ground-state enol tautomer, whereas thermally activated cis-keto and photoisomerised trans-keto states exist as low-level defects with populations that are too low to detect experimentally. Variable temperature ¹³C NMR data reveal evidence for solid-state dynamics, which is found to be associated with fast rotational motion of t-butyl groups and 180° flips of the pyridine ring, contrasting the time-averaged structure obtained by X-ray diffraction. Comparison of calculated chemical shifts for the full crystal structure and an isolated molecule also reveals evidence for an intermolecular hydrogen bond involving the pyridine ring and an adjacent imine carbon, which facilitates the flipping motion. The DFT calculations also reveal that the molecular conformation in the crystal structure is very close to the energetic minimum for an isolated molecule, indicating that the ring dynamics arise as a result of considerable steric freedom of the pyridine ring and which also allows the molecule to adopt a favourable conformation for photochromism.     

Stabilising Peptoid Helices Using Non‐Chiral Fluoroalkyl Monomers

Stability towards protease degradation combined with modular synthesis has made peptoids of considerable interest in the fields of chemical biology, medicine, and biomaterials. Given their tertiary amide backbone, peptoids lack the capacity to hydrogen‐bond, and as such, controlling secondary structure can be challenging. The incorporation of bulky, charged, or chiral aromatic monomers can be used to control conformation but such building blocks limit applications in many areas. Through NMR and X‐ray analysis we demonstrate that non‐chiral neutral fluoroalkyl monomers can be used to influence the K_cis/trans equilibria of peptoid amide bonds in model systems. The cis‐isomer preference displayed is highly unprecedented given that neither chirality nor charge is used to control the peptoid amide conformation. The application of our fluoroalkyl monomers in the design of a series of linear peptoid oligomers that exhibit stable helical structures is also reported.     

Conformational equilibrium in 8-methyl-cis-2-thiahydrindane and 8-methyl-cis-2-oxahydrindane by 13C NMR spectroscopy

The preferred conformation of 8-methyl-cis-thiahydrindane has been both estimated by ¹³C NMR chemical shifts and determined by low temperature ¹³C NMR spectroscopy to be the conformer with the methyl group equatorial with respect to the cyclohexane ring. This result is in disagreement with the interpretation of the temperature dependence of the CD spectra of (+) and (?) 8-methyl-cis-2-thiahydrindane, whereby the conformation with the methyl group axial with respect to the cyclohexane ring was claimed to be the preferred conformation. The preferred conformation of the related oxygen heterocycle, 8-methyl-cis-2-oxahydrindane, has been estimated by ¹³C NMR chemical shifts to be the conformer with the methyl group axial with respect to the cyclohexane ring. Possible reasons for these observations are discussed.     

Structural analysis of pentacyclic triterpenes from the gum resin of Boswellia serrata by NMR spectroscopy

3α‐Acetyl‐β‐boswellic acid ( 1 ), 3α‐acetyl‐α‐boswellic acid ( 2 ), 3α‐acetyl‐9,11‐dehydro‐β‐boswellic acid ( 3 ), 3α‐acetyl‐9,11‐dehydro‐α‐boswellic acid ( 4 ) and 3α‐acetyl‐11‐keto‐β‐boswellic acid ( 5 ) were isolated from the gum resin of Boswellia serrata. 1D and 2D NMR (COSY45, HMQC, HMBC, ROESY) spectra at 500 MHz were used for shift assignments and structure verification. All boswellic acids investigated share the cis conformation at ring D/E and the 3α orientation of the acetyl ester group. Owing to high‐order spectra, NMR could not determine the exact conformation of H‐20/H‐30 of the β‐boswellic acids. 3α‐Acetyl‐β‐boswellic acid methyl ester ( 1 ^′) was synthesized for experiments with a shift reagent, Eu(fod)₃, that enhanced the resolution considerably. The oxygen atoms of the 3α‐acetyl group form the apparent complex binding site for the shift reagent. Copyright © 2003 John Wiley & Sons, Ltd.     

Stereochemical studies-XIV: Cyclic amino alcohols and related compounds-VII

1,3-Tetrahydro-oxazine-2-ones were prepared by the reaction of cis- and trans-2-hydroxymethylcyclohexylamine, as well as cis- and trans-2-aminomethylcyclohexanol with carbamide. Their structure and stereochemical purity were proved by IR and NMR investigations. With the help of the NMR spectra the conformation of these compounds was established. The trans isomers exist in stable chair-chair conformation. Two chair-chair conformations are possible in the case of the cis isomers; one in which the heteroatom and the methylene group of the heteroring are axial and equatorial, respectively and the second in which their positions are reversed. It was proved that the cis isomers are conformationally homogeneous, having the hetero atom in axial position.     

Ruthenium Lewis Acid‐Catalyzed Asymmetric Diels–Alder Reactions: Reverse‐Face Selectivity for α,β‐Unsaturated Aldehydes and Ketones

Acrolein, methacrolein, methyl vinyl ketone, ethyl vinyl ketone, 3‐methyl‐3‐en‐2‐one, and divinyl ketone were coordinated to a cationic cyclopentadienyl ruthenium(II) Lewis acid incorporating the electron‐poor bidentate BIPHOP–F ligand. Analysis by NOESY and ROESY NMR techniques allowed the determination of conformations of enals and enones present in solution in CD₂Cl₂. The results were compared to solid‐state structures and to the facial selectivities of catalytic asymmetric Diels–Alder reactions with cyclopentadiene. X‐Ray structures of four Ru‐enal and Ru‐enone complexes show the α,β‐unsaturated C=O compounds to adopt an anti‐s‐trans conformation. In solution, enals assume both anti‐s‐trans and anti‐s‐cis conformations. An additional conformation, syn‐s‐trans, is present in enone complexes. Enantioface selectivity in the cycloaddition reactions differs for enals and enones. Reaction products indicate enals to react exclusively in the anti‐s‐trans conformation, whereas with enones, the major product results from the syn‐s‐trans conformation. The alkene in s‐cis conformations, while present in solution, is shielded and cannot undergo cycloaddition. A syn‐s‐trans conformation is found in the solid state of the bulky 6,6‐dimethyl cyclohexanone‐Ru(II) complex. The X‐ray structure of divinyl ketone is unique in that the Ru(II) center binds the enone via a η² bond to one of the alkene moieties. In solution, coordination to Ru–C=O oxygen is adopted. A comparison of facial preference is also made to the corresponding indenyl Lewis acids.     

Optically Pure,Monodisperse cis‐Oligodiacetylenes: Aggregation‐Induced Chirality Enhancement

Conformational changes in the conjugated backbone of poly‐ and oligodiacetylenes (PDAs and ODAs) play an important role in determining the electronic properties of these compounds. At the same time, conformational changes can also result in a folded structure that shows helical chirality. Using D ‐camphor as a chiral building block, we have designed a high‐yielding, iterative synthesis of monodisperse, optically pure cis‐oligodiacetylenes (ODAs). cis‐ODAs up to the tridecamer have been formed, which is the longest monodisperse cis‐ODA reported to date. UV/Vis spectroscopy suggests a large effective conjugation length in THF, likely the result of a linear, planar conformation in this solvent. High‐resolution STM/AFM measurements of the nonamer cast from THF onto HOPG show a linear structure. In iPrOH, circular dichroism (CD) spectra suggest the formation of chiral aggregates for ODAs with at least nine D ‐camphor units, based on a strong CD response.     

12H-dibenzo[d,g][1,3,2]dioxaphosphocins: Synthesis,structures and “through-space” spin-spin coupling in their NMR spectra

A series of 12H-dibenzo[d,g][1,3,2]dioxaphosphocins has been prepared by the reactions of bisphenols with either ethyl phosphorodichloridate or phosphorus pentasulfide. The structures of a pair of cis and trans isomers in this series were elucidated by X-ray crystallography. Both isomers adopt the boat-chair conformation in the solid state with the bulky group at C-12 in the pseudo-equatorial position. Some flattening of the heterocyclic ring due to the pseudo-axial ethoxy group was observed in the cis isomer. A novel transannular cyclisation reaction was observed in the mass spectra of the cis isomers and this has allowed us to assign the configurations of all the isomers in the series. The pmr spectra of the compounds have been explained in terms of the rigid boat-chair conformation; however, as bulky groups were introduced at C-12, signs of mobility were observed for the cis isomers and an equilibrium was established with mobile boat forms. A stereospecific long-range coupling between P and the proton at C-12 could be transmitted “through space” by the antiperiplanar lone-pair electrons on the ring oxygen atoms.     

Benzo- and indoloquinolizine derivatives. VI—configuration and conformation of 4b,5,6,7,8,8a,10,11,16,16b-decahydrodibenz[f,h]indolo[2,3-a]quinolizine diastereoisomers. A 270 MHz 1H NMR study

The synthesis of a D/E cis isomer of the title compound is described. In an attempt to obtain the other D/E cis isomer, epimerisation reactions were studied. The configuration and conformation of the isomers are determined on the basis of their ¹H NMR spectra. The shift of the 16b proton on N-9 protonation indicates the quinolizidine conformation. At 270 MHz, the ABCD system of the C-10 and C-11 methylenes can be analysed. The ²J(C-10H₂), together with the multiplicity of H-8a, allows an unequivocal assignment of a cis-anti-cis structure to the only D/E cis isomer obtained.     

SYNTHESIS AND CRYSTAL STRUCTURE OF A BINUCLEAR COPPER (II) COMPLEX BRIDGED BY OXAMIDATO,Cu2(μ-CIS-OXPN)(PHEN)(NO3)2

Abstract

The complex [Cu₂(μ-cis-oxpn)(phen)(NO₃)₂], where oxpn = N,N′ -bis(3-aminopropyl) oxamidato and phen = 1,10-phenanthroline, has been synthesized and its crystal structure determined by X-ray methods. The structure consists of binuclear copper (II) molecules in which the Cu(II) atoms are bridged by oxamidato group in the cis conformation, the Cu—Cu distance being 5.205(10) Å. The coordination geometry around Cu (II) atoms is square pyramidal; the apex is occupied by a more weakly bonded O atom from a nitrate group. Electron delocalization is observed in the bridging oxamide moiety. The co-planarity of bridge ligand and basal plane around Cu (II) atoms may benefit spin super-exchange between two Cu (II) atoms. IR spectra of the binuclear complex are discussed.     

Über Pterinchemie. Mitteilung. Die Kristallstruktur von 5,6,7-Trimethyl-5,6,7,8-tetrahydropterindihydrochlorid-monohydrat

The crystal structure of 5,6,7-trimethyl-5,6,7,8-tetrahydropterine-dihydrochloride-monohydrate The crystal structure of the title compound has been determined by X-ray analysis (direct methods) and refined with 947 structure amplitudes to R = 0.026. The crystal system is orthorhombic, space group Pna2₁, with unit cell dimensions a = 14.081, b = 14.623, c = 6.773 Å. The molecule is protonated at the N(1)- and N(5)-position. The tetrahydropyrazine ring exists in a conformation in which C(6) deviates markedly from the mean plane of the other five atoms. The CH₃-groups at N(5) and C(6) possess a trans configuration with a pseudoaxial and an axial conformation respectively. The CH₃-groups at C(6) and C(7) in return possess the cis configuration, whereby the CH₃-group at C(7) occupies an equatorial conformation.     

Crystal and molecular structure of 6-(p-iodobenzenesulfonyl)-3-oxa-6-azabicyclo[3.1.0]hexane

The crystal and molecular structure of 6-(p-iodobenzenesulfonyl)-3-oxa-6-azabicyclo-[3.1.0]hexane has been determined by a three-dimensional single-crystal x-ray diffraction study. The compound crystallizes in the monoclinic space group C₂/c with cell dimensions, a = 19.76, b = 8.17, c = 15.72 ± 0.003 Å and β = 109.3° ± 0.2°. The aziridine ring is fused cis to the oxa-cyclopentane ring with fusion angles of 112°. The bicyclic system is in the boat conformation with the p-iodobenzenesulfonate group at an angle of 98.0° to it. The conformation of the ring system is discussed. A final value of R = 0.099 was obtained for the 1107 independent reflections.     

Methyl 4‐O‐benzoyl‐2,3‐O‐isopropyl­idene‐α‐l‐rhamnopyran­oside

The title compound, C₁₇H₂₂O₆, has an exocyclic ester group at the hexopyranosyl sugar residue. The carbonyl group shows a conformation that is eclipsed with respect to the adjacent ring C—H bond. The two ester torsion angles are denoted by syn and cis conformations. One of these torsion angles is indicated to have a similar conformation in solution, as analyzed by NMR spectroscopy and a Karplus‐type relationship.     

Molecular and crystal structure of <Emphasis Type="Italic">trans</Emphasis> and <Emphasis Type="Italic">cis</Emphasis> isomers of 3-cyano-4-[2-(4-methoxyphenyl)vinyl]-6,6-dimethyl-5,6-dihydro-2H-pyran

Monocrystals of the trans and cis isomers of 3-cyano-4-[2-(4-methoxyphenyl)vinyl]-6,6-dimethyl-5,6-dihydro-2H-pyran have been obtained and an X-ray structural analysis of them has been carried out. Both compounds have a molecular structure corresponding to symmetry group C₁. The heterocyclic ring is in a distorted envelope conformation. The crystals of the trans isomer are rhombic and have a fir-tree type of packing. The crystal packing of the cis isomer is formed by pairs of molecules, each of which consists of only one enantiomer. *Dedicated to deeply respected Professor Hank van der Plas in connection with his jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 535-540, April, 2009.     

The crystal structure and conformation of 15-phenyl-bicyclo[10.3.0]pentadec-1(12)-en-13-one

The title compound has been synthesized and its crystal structure determined by X-ray crystallographic method. The crystal is monoclinic, space group C2/c, with unit cell dimensions a=19.260 (3), b=11.217 (1), c=15.997 (1) Å; β=92.08 (2)° and Z=8. This is the first crystal structure determined in the series of bicyclo[10.3.0]pentadec-1(12)-en-13-one derivatives. The structure and the conformation of the cis-cyclododecene moiety in this compound is demonstrated to be closely similar to the lowest energy conformer [lene 2333].     

Light Dynamics of the Retinal‐Disease‐Relevant G90D Bovine Rhodopsin Mutant

The RHO gene encodes the G‐protein‐coupled receptor (GPCR) rhodopsin. Numerous mutations associated with impaired visual cycle have been reported; the G90D mutation leads to a constitutively active mutant form of rhodopsin that causes CSNB disease. We report on the structural investigation of the retinal configuration and conformation in the binding pocket in the dark and light‐activated state by solution and MAS‐NMR spectroscopy. We found two long‐lived dark states for the G90D mutant with the 11‐cis retinal bound as Schiff base in both populations. The second minor population in the dark state is attributed to a slight shift in conformation of the covalently bound 11‐cis retinal caused by the mutation‐induced distortion on the salt bridge formation in the binding pocket. Time‐resolved UV/Vis spectroscopy was used to monitor the functional dynamics of the G90D mutant rhodopsin for all relevant time scales of the photocycle. The G90D mutant retains its conformational heterogeneity during the photocycle.     

Carbon-13 nuclear magnetic resonance spectra and conformations of cis,cis-1,5-cyclooctadiene monoepoxide and cis,syn,cis-1,5-cyclooctadiene diepoxide

The natural-abundance ¹³C NMR spectra of cis,cis-1,5-cyclooctadiene monoepoxide and cis,syn,cis-1,5-cyclooctadiene diepoxide have been investigated over the temperature range of – 10 to – 180°C. Whereas the spectra of the former showed no dynamic NMR effect, two different conformations in the ratio of 3:1 were observed at low temperatures for the latter. The free-energy barrier (ΔG^≠) for conversion of the major conformation to the minor conformation is calculated to be 5.9°0.2 kcal mol^?1 from a line-shape analysis of spectra obtained at intermediate temperatures. It is shown that cis,syn,cis-1,5-cyclooctadiene diepoxide exists in solution in chair (major) and in twist-boat (minor) conformations of slightly different energies. Interconversion paths between these conformations are discussed. The monoepoxide is suggested to have a twist-boat conformation that is rapidly pseudorotating via a boat conformation even at – 180°C.     

Dinuclear Tin(II) Complex of a Bulky cis‐Oxamide: Synthesis,Characterization, Crystal Structure,and DFT Studies

The reaction of the di‐lithiated oxamide of 1 with two equivalents of SnCl₂ provided the tin trans‐oxamide 3 . In solution, spectroscopic analysis suggests exclusively the formation of a trans‐oxamide (trans‐ 3 ). However, the solid state shows an atypical cis‐oxamide (cis‐ 3 ), where the oxamide fragment acts as an anti‐Janus head ligand. An ¹¹⁹Sn‐NMR variable temperature experiment ([D₈]THF) of the trans‐oxamide (trans‐ 3 ) was performed however, at lower temperature no additional signal was observed, which confirmed the absence of a dynamic equilibrium. Dispersion‐corrected density functional calculations revealed that the cis conformation of this tin(II) oxamide complex is more stable than the trans isomer by 1.4 kcal · mol^–1.