S-trans Conformation Research Articles

Crystal structure of N-{N-[N-(tert-but-oxy-carbon-yl)-l-α-aspart-yl]-l-α-aspart-yl}-l-α-aspartic acid 14,24,34-trimethyl ester 31-2-oxo-2-phenyl-ethyl ester {Boc-[Asp(OMe)]3-OPac}.

In the title homotripeptide {Boc-[Asp(OMe)]3-OPac}, C28H37N3O13, all peptide bonds adopt an s-trans conformation with respect to the N-H and C=O groups. In the crystal, N-H⋯O hydrogen bonds result in an infinite parallel β-sheet structure running along the b-axis direction. The Boc protecting group at the N-terminus of the peptide is disordered over two sites with occupancy factors of 0.504 (5) and 0.496 (5).

Iridium(I) homobinuclear complexes containing salen-type ligands as bridge

New binuclear iridium(I) complexes with general formula [Ir2(η4-cod)2(μ-SB)] (1–12) derived from the reactions of tetradentate Schiff bases ligands [N,N′-ethylenebis(5-R-salicylideneimine)] (5,5′-R-salenH2), [N,N′-1,3-propylenebis(5-R-salicylideneimine)] (5,5′-R-salpenH2), and [N,N′-o-phenylenebis(5-R-salicylideneimine)] (5,5′-R-salphenH2) (R = H, MeO, Cl, NO2) with [Ir(cod)(μ-Cl)]2 were synthesized. The homobinuclear nature of this iridium complexes was supported by elemental analysis, FAB-Mass and 1H NMR spectrometry. Full characterization was accomplished by IR spectroscopy, 13C NMR and bidimensional NMR experiments (COSY, HSQC, HMBC and NOESY). In addition, iridium complex [(Ir(η4-cod)2(μ-5,5′-MeO-salen)] (2) was characterized by X-ray crystallography, showing that ethylene bridge is a s-trans conformation, and that the Schiff base ligand act as a bridging N,O-bidentate ligand toward two iridium atoms, and 1,5-cyclooctadiene (cod) ligand complete the coordination sphere of metal center. The effect of the substituent groups on salicylaldiminate fragments has been studied by 13C{1H} NMR shift and Hammett sigma correlations for each series of complexes.

Stereogenic cyclic oligonaphthalenes displaying ring size-dependent handedness of circularly polarized luminescence (CPL).

A series of cyclic oligomers with Dn symmetry (n = 2-5) based on chiral (R)/(S)-binaphthyl exhibiting intensive chiroptical properties were synthesized by using a Ni(0)-catalyzed coupling reaction. The intensity and the handedness of circularly polarized luminescence (CPL) were dependent on the ring size of the cyclic oligomers, in which the 1,1'-binaphthyl moieties form s-cis (n = 2, 3) or s-trans (n = 4, 5) conformers in the excited state. The relationship between the structure and chiroptical properties is discussed with the aid of X-ray analysis and DFT calculations.

Homo- and heterobimetallic azines derived from ferrocene and cyrhetrene: Synthesis, structural characterization and electrochemical studies

A new series of asymmetrical heterobimetallic azines [(η5-C5H5)Fe{(η5-C5H4)C(R) = NNC(R1)-(η5-C5H4)Re(CO)3}] (1–3) and symmetrical homobimetallic cyrhetrenyl azines [{(η5-C5H4)C(R) = N}Re(CO)3]2 (4, 5) have been synthesized and were spectroscopically characterized by FT-IR, NMR, EI-MS and cyclic voltammetry. The molecular structures of 1 and 4 were determined using single-crystal X-ray diffraction technique. Based on the oxidation potential of the ferrocenyl units and the high degree of planarity of the [(C5H4)C(H) = NNC(H)-(C5H4)] system in complex 1, we inferred electronic communication between the electron-withdrawing cyrhetrenyl groups through the π-conjugated azine bridge. The compounds display an (E,E)-configuration about the >CN- bond, an s-trans conformation for the NN bond and an anti-conformation for the two organometallic fragments.

SN2″-Selective and Enantioselective Substitution with Unsaturated Organoboron Compounds and Catalyzed by a Sulfonate-Containing NHC-Cu Complex.

The first broadly applicable strategy for SN2″-selective and enantioselective catalytic substitution is disclosed. Transformations are promoted by 5.0 mol% of a sulfonate-containing NHC-Cu complex (NHC = N-heterocyclic carbene), and are carried out in the presence of commercially available allenyl-B(pin) (pin = pinacolato) or a readily accessible silyl-protected propargyl-B(pin). Acyclic, or aryl-, heteroaryl-, and alkyl-substituted penta-2,4-dienyl phosphates, as well as those bearing either only 1,2-disubstituted olefins or a 1,2-disubstituted and a trisubstituted alkene were found to be suitable starting materials. Cyclic dienyl phosphates may also serve as substrates. The products containing, in addition to a 1,3-dienyl group, a readily functionalizable propargyl moiety (from reactions with allenyl-B(pin)) were obtained in 51-82% yield, 84-97% SN2″ selectivity, 89:11-97:3 E: Z ratio, and 86:14-98:2 enantiomeric ratio (er). Reactions with a silyl-protected propargyl-B(pin) compound led to the formation of the corresponding silyl-allenyl products in 53-89% yield, 69-96% SN2″ selectivity, 98:2 to >98:2 E: Z ratio, and 94:6-98:2 er. Insight regarding several of the unique mechanistic attributes of the catalytic process was obtained on the basis of kinetic isotope effect measurements and DFT studies. These investigations indicate that cationic π-allyl-Cu complexes are likely intermediates, clarifying the role of the s-cis and s-trans conformers of the intermediate organocopper species and their impact on E: Z selectivity and enantioselectivity. The utility of the approach is demonstrated by chemoselective functionalization of various product types, through which the propargyl, allenyl, or 1,3-dienyl sites within the products have been converted catalytically and chemoselectively to several useful derivatives.

Influence of piperidine ring on stability and reactivity of piperine

The influence of piperidine ring on chemical reactivity and stability of piperine (PPN) was elucidated using quantum chemistry calculations with Density Functional Theory at DFT/B3LYP/6-31G(d,p) level of theory. Conformational analysis and electronic properties for PPN were compared to piperic acid (PPA). Piperidine ring has displayed great influence on steric-electronic properties of PPN, especially among aromatic ring, carbonyl moiety and alkenes system, respectively. All s-trans conformers showed higher stability when compared to s-cis conformers. The lower GapL-H for PPA showed that it is more reactive than PPN, providing that PPN is more nucleophilic than PPA and PPA is more electrophilic than PPN. In conclusion, piperidine ring is related to the chemical stability of PPN, through steric and electronic properties.

The compound millepachine and its derivatives inhibit tubulin polymerization by irreversibly binding to the colchicine-binding site in β-tubulin

Inhibitors that bind to the paclitaxel- or vinblastine-binding sites of tubulin have been part of the pharmacopoeia of anticancer therapy for decades. However, tubulin inhibitors that bind to the colchicine-binding site are not used in clinical cancer therapy, because of their low therapeutic index. To address multidrug resistance to many conventional tubulin-binding agents, numerous efforts have attempted to clinically develop inhibitors that bind the colchicine-binding site. Previously, we have found that millepachine (MIL), a natural chalcone-type small molecule extracted from the plant Millettia pachycarpa, and its two derivatives (MDs) SKLB028 and SKLB050 have potential antitumor activities both in vitro and in vivo However, their cellular targets and mechanisms are unclear. Here, biochemical and cellular experiments revealed that the MDs directly and irreversibly bind β-tubulin. X-ray crystallography of the tubulin-MD structures disclosed that the MDs bind at the tubulin intradimer interface and to the same site as colchicine and that their binding mode is similar to that of colchicine. Of note, MDs inhibited tubulin polymerization and caused G2/M cell-cycle arrest. Comprehensive analysis further revealed that free MIL exhibits an s-cis conformation, whereas MIL in the colchicine-binding site in tubulin adopts an s-trans conformation. Moreover, introducing an α-methyl to MDs to increase the proportion of s-trans conformations augmented MDs' tubulin inhibition activity. Our study uncovers a new class of chalcone-type tubulin inhibitors that bind the colchicine-binding site in β-tubulin and suggests that the s-trans conformation of these compounds may make them more active anticancer agents.

(E)-1,3-Bis(anthracen-9-yl)prop-2-en-1-one: crystal structure and DFT study.

The title compound, C31H20O, was synthesized using a Claisen-Schmidt condensation. The enone group adopts an s-trans conformation and the anthracene ring systems are twisted at angles of 85.21 (19) and 83.98 (19)° from the enone plane. In the crystal, mol-ecules are connected into chains along [100] via weak C-H⋯π inter-actions. The observed band gap of 3.03 eV is in excellent agreement with that (3.07 eV) calculated using density functional theory (DFT) at the B3LYP/6-311++G(d,p) level. The Hirshfeld surface analysis indicates a high percentage of C⋯H/H⋯C (41.2%) contacts in the crystal.

Crystal structure of 3-[(2-acetamido-phen-yl)imino]-butan-2-one.

In the title compound, 3-[(2-acetamido-phen-yl)imino]-butan-2-one, C12H14N2O2, the imine C=N bond is essentially coplanar with the ketone C=O bond in an s-trans conformation. The benzene ring is twisted away from the plane of the C=N bond by 53.03 (14)°. The acetamido unit is essentially coplanar with the benzene ring. In the crystal, mol-ecules are connected into chains along the c axis through C-H⋯O hydrogen bonds, with two adjacent chains being hinged by C-H⋯O hydrogen bonds.

Conformational Landscape and Torsion-Rotation-Vibration Effects in the Two Conformers of Methyl Vinyl Ketone, a Major Oxidation Product of Isoprene.

Methyl vinyl ketone is the second major oxidation product of isoprene, and as such an important volatile organic compound present in the troposphere. In the present study, quantum chemical calculations coupled to high-resolution millimeter-wave spectroscopy have been performed to characterize the ground and first excited vibrational states of the two stable conformers. Equilibrium structures, internal rotation barriers, and relative energies have been calculated at the MP2 and M062X levels of theory. Experimental molecular parameters have been obtained that model the rotational and torsional structures, including splitting patterns due to the internal rotation of the methyl group. For the most stable antiperiplanar (s-trans) conformer, the set of parameters obtained for the ground state should be useful to further model IR spectra up to room temperature. By combining theoretical and experimental data, we obtained a relative energy value of 164 ± 30 cm-1 in the gas phase between the more stable antiperiplanar and the less stable synperiplanar conformers. Moreover, we compared our system with related molecules for the variation in the barriers of methyl rotors in different molecular environments. In addition, the inverse sequence of A and E tunneling substates for the rotational lines of the first excited skeletal torsional state and Coriolis-type coupling with methyl torsion have been observed. For the less stable synperiplanar (cis) conformer, molecular parameters for the ground and first excited torsional states as well as of the first excited skeletal torsional state are presented.

Structure determination of myrtenal by microwave spectroscopy and quantum chemical calculations

The rotational spectrum of myrtenal has been investigated using a Fourier transform microwave spectrometer coupled to a supersonic expansion in the 2–20GHz frequency range. Of the two possible conformers expected in the gas phase, only the s-trans conformer which was calculated 12kJmol-1 lower in energy than the s-cis conformer was observed. The spectra of the ten 13C and 18O isotopic species of s-trans-myrtenal were observed in natural abundance. The ground state rotational constants are A=1666.269706(55)MHz,B=962.344291(40)MHz and C=836.903508(43)MHz. A partial rs structure was calculated using Kraitchman’s equations. A r0 structure was also derived using additional data from a B3LYP/6-311++G(d,p) calculation. The structural parameters of the CCCO pattern of myrtenal (r0(CC)=1.341(16)Å, r0(CC)=1.479(98)Å, r0(CO)=1.220(13)Å, ∠(OCC)=124.4(13)° and ∠(CCC)=119.3(11)°) are very close to those in trans-acrolein and in trans-trans-cinnamaldehyde.

Binuclear zinc(II) complexes of N(4)-substituted bis(thiosemicarbazone) ligands incorporating hydroxyl group and their non-hydroxyl analogues

We have reported the synthesis and physical and chemical studies of the new zinc complexes of N(4)-substituted bis(thiosemicarbazones). The complexes characterized by spectroscopic methods. The crystal structures of the compounds [Zn2L2(CH3COO)]·EtOH and [Zn2L4(CH3COO)]·MeOH is determined. Bis(thiosemicarbazones) involving a pendant OH group having SNONS donor sequences can hold two metal ions in close proximity. The coordination sphere has been formed by the imine nitrogen and sulfur atom, and the remaining positions, in a square-based pyramid, has been occupied by three oxygen atoms derived of pendant OH, ether group and acetate ligand. Acetate ligand and alkoxide oxygen are bridged between two metal centers. Whereas, their non-hydroxyl analogues are dimer. In dimer complexes, two ligands are tetradentate coordinated via N2S2 donor atoms. The presence of bulky groups on the nitrogens of thiosemicarbazide enforce an s-trans conformation for the H2L1 and H2L3 ligands in [ZnL1]2·MeOH and [ZnL3]2·MeOH. Fluorescence studies suggest that the [ZnL1]2·MeOH complex can be utilized as a fluorescent imaging agent.

Quantitative Infrared Absorption Spectra and Vibrational Assignments of Crotonaldehyde and Methyl Vinyl Ketone Using Gas-Phase Mid-Infrared, Far-Infrared, and Liquid Raman Spectra: s-cis vs s-trans Composition Confirmed via Temperature Studies and ab Initio Methods.

Methyl vinyl ketone (MVK) and crotonaldehyde are chemical isomers; both are also important species in tropospheric chemistry. We report quantitative vapor-phase infrared spectra of crotonaldehyde and MVK vapors over the 540-6500 cm-1 range. Vibrational assignments of all fundamental modes are made for both molecules on the basis of far- and mid-infrared vapor-phase spectra, liquid Raman spectra, along with density functional theory and ab initio MP2 and high energy-accuracy compound theoretical models (W1BD). Theoretical results indicate that at room temperature the crotonaldehyde equilibrium mixture is approximately 97% s-trans and only 3% s-cis conformer. Nearly all observed bands are thus associated with the s-trans conformer, but a few appear to be uniquely associated with the s-cis conformer, notably ν16c at 730.90 cm-1, which displays a substantial intensity increase with temperature (70% upon going from 5 to 50 o C). The intensity of the corresponding mode of the s-trans conformer decreases with temperature. Under the same conditions, the MVK equilibrium mixture is approximately 69% s-trans conformer and 31% s-cis. W1BD calculations indicate that for MVK this is one of those (rare) cases where there are comparable populations of both conformers, approximately doubling the number of observed bands and exacerbating the vibrational assignments. We uniquely assign the bands associated with both the MVK s-cis conformer as well as those of the s-trans, thus completing the vibrational analyses of both conformers from the same set of experimental spectra. Integrated band intensities are reported for both molecules along with global warming potential values. Using the quantitative IR data, potential bands for atmospheric monitoring are also discussed.

Fluorescence excitation spectra of all-trans-1,6-diphenylhexatriene conformers: Adiabatic conformer equilibration in the 21Ag state

Fluorescence spectra of all-trans-1,6-diphenyl-1,3,5-hexatriene were measured in n-hexadecane at 99°C by varying λexc in the 294–404nm range. Resolution of this spectral matrix into s-trans,s-trans and s-cis,s-trans conformer fluorescence spectra yields the λexc dependence of fractional contributions which are converted to conformer specific fluorescence excitation spectra. Conformer absorption spectra obtained from the fluorescence excitation spectra are remarkably similar, but differ significantly from absorption spectra derived from a spectrothermal absorption spectral matrix measured in n-alkanes under isopolarizability conditions. The results reveal substantial conformer equilibration in the excited state. Theory is consistent with adiabatic conformer equilibration in the 21Ag state.

Torsion-rotation-vibration effects in the ground and first excited states of methacrolein, a major atmospheric oxidation product of isoprene.

Methacrolein is a major oxidation product of isoprene emitted in the troposphere. New spectroscopy information is provided with the aim to allow unambiguous identification of this complex molecule, characterized by a large amplitude motion associated with the methyl top. State-of-the-art millimeter-wave spectroscopy experiments coupled to quantum chemical calculations have been performed. For the most stable s-trans conformer of atmospheric interest, the torsional and rotational structures have been characterized for the ground state, the first excited methyl torsional state (ν27), and the first excited skeletal torsional state (ν26). The inverse sequence of A and E tunneling sub-states as well as anomalous A-E splittings observed for the rotational lines of v26 = 1 state clearly indicates a coupling between methyl torsion and skeletal torsion. A comprehensive set of molecular parameters has been obtained. The far infrared spectrum of Durig et al. [Spectrochim. Acta, Part A 42, 89-103 (1986)] was reproduced, and a Fermi interaction between ν25 and 2ν27 was evidenced.

Computational Examination of (4 + 3) versus (3 + 2) Cycloaddition in the Interception of Nazarov Reactions of Allenyl Vinyl Ketones by Dienes.

A computational examination of the tandem Nazarov/cycloaddition process involving an allenyl vinyl ketone with a diene has been carried out using the ωB97X-D/6-311++G(d,p)//ωB97X-D/6-31+G(d,p) method with solvation modeled by SMD-PCM. The barrier for the initial Lewis acid mediated Nazarov reaction, which provided the intermediate cyclic oxylallyl cation, was higher than that for any subsequent cycloaddition. The barrier for the first step of a subsequent stepwise reaction did not vary much with the diene, and the lowest barrier was with the diene in its s-trans conformation. Stepwise formation of a (4 + 3) cycloaddition product was not energetically feasible, but (3 + 2) cycloaddition products could have been produced through low energy pathways. The barrier for a concerted (4 + 3) cycloaddition did depend upon the diene, which was always in an s-cis geometry. The barriers for the compact and the extended geometries for the transition states of (4 + 3) cycloadditions were not much different.

Chiral Lithiated Allylic α-Sulfonyl Carbanions: Experimental and Computational Study of Their Structure, Configurational Stability, and Enantioselective Synthesis.

X-ray crystal structure analysis of the lithiated allylic α-sulfonyl carbanions [CH2 CHC(Me)SO2 Ph]Li⋅diglyme, [cC6 H8 SO2 tBu]Li⋅PMDETA and [cC7 H10 SO2 tBu]Li⋅PMDETA showed dimeric and monomeric CIPs, having nearly planar anionic C atoms, only OLi bonds, almost planar allylic units with strong CC bond length alternation and the s-trans conformation around C1C2. They adopt a C1S conformation, which is similar to the one generally found for alkyl and aryl substituted α-sulfonyl carbanions. Cryoscopy of [EtCHCHC(Et)SO2 tBu]Li in THF at 164 K revealed an equilibrium between monomers and dimers in a ratio of 83:17, which is similar to the one found by low temperature NMR spectroscopy. According to NMR spectroscopy the lone-pair orbital at C1 strongly interacts with the CC double bond. Low temperature (6) Li,(1) H NOE experiments of [EtCHCHC(Et)SO2 tBu]Li in THF point to an equilibrium between monomeric CIPs having only OLi bonds and CIPs having both OLi and C1Li bonds. Ab initio calculation of [MeCHCHC(Me)SO2 Me]Li⋅(Me2 O)2 gave three isomeric CIPs having the s-trans conformation and three isomeric CIPs having the s-cis conformation around the C1C2 bond. All s-trans isomers are more stable than the s-cis isomers. At all levels of theory the s-trans isomer having OLi and C1Li bonds is the most stable one followed by the isomer which has two OLi bonds. The allylic unit of the C,O,Li isomer shows strong bond length alternation and the C1 atom is in contrast to the O,Li isomer significantly pyramidalized. According to NBO analysis of the s-trans and s-cis isomers, the interaction of the lone pair at C1 with the π* orbital of the CC double bond is energetically much more favorable than that with the "empty" orbitals at the Li atom. The C1S and C1C2 conformations are determined by the stereoelectronic effects nC -σSR * interaction and allylic conjugation. (1) H DNMR spectroscopy of racemic [EtCHCHC(Et)SO2 tBu]Li, [iPrCHCHC(iPr)SO2 tBu]Li and [EtCHC(Me)C(Et)SO2 tBu]Li in [D8 ]THF gave estimated barriers of enantiomerization of ΔG(≠) =13.2 kcal mol(-1) (270 K), 14.2 kcal mol(-1) (291 K) and 14.2 kcal mol(-1) (295 K), respectively. Deprotonation of sulfone (R)-EtCHCHCH(Et)SO2 tBu (94 % ee) with nBuLi in THF at -105 °C occurred with a calculated enantioselectivity of 93 % ee and gave carbanion (M)-[EtCHCHC(Et)SO2 tBu]Li, the deuteration and alkylation of which with CF3 CO2 D and MeOCH2 I, respectively, proceeded with high enantioselectivities. Time-dependent deuteration of the enantioenriched carbanion (M)-[EtCHCHC(Et)SO2 tBu]Li in THF gave a racemization barrier of ΔG(≠) =12.5 kcal mol(-1) (168 K), which translates to a calculated half-time of racemization of t1/2 =12 min at -105 °C.

Unsymmetrical cyrhetrenyl and ferrocenyl azines derived from 5-nitrofurane: Synthesis, structural characterization and electrochemistry

A new series of unsymmetrical cyrhetrenyl and ferrocenyl azines that were monosubstituted [(η5-C5H4)–C(R)N–NCH(5-NO2–2-C4H2O)]M {with MRe(CO)3 and RH (1a) or RMe (1b); MFe(η5-C5H5) and RH (2a) or RMe (2b)} and disubstituted [Fe{(η5-C5H4)–C(Me)N–NCH(5-NO2–2-C4H2O)}2] (3a) were prepared by condensation reactions of the corresponding organometallic hydrazone [(η5-C5H4)–C(R)N–NH2)]M with 5-nitro-2-furaldehyde. The 1H and 13C{1H} NMR spectra indicated that these compounds adopted an (E,E)-configuration about the ˃CN− bond and an s-trans conformation about the N1–N2 bond, and this result was confirmed by X-ray crystallographic analyses of 1a and 2b. The opposite electronic effects of the organometallic fragments correlate with the co-planarity of the [(η5-C5H4)–C(R)N–NCH(5-NO2–2-C4H2O)] system, the reduction potential of the nitro group (E1/2) and the chemical shifts of the iminic carbons.

Comment on ‘On Saltiel's isopolarizability approach and its applicability to diphenylpolyenes’ by J. Catalán, Chem. Phys. Lett. 635 (2015) 56–59

This is in response to Catalán's objection to our use of isopolarizability conditions in the resolution of the absorption and fluorescence spectra of the s-cis and s-trans all-trans-1.6-diphenyl-1,3,5-hexatriene (ttt-DPH) conformers and the resolution of the fluorescence spectrum of the s-trans conformer to 21Ag→11Ag and 11Bu→11Ag spectra. Contrary to Catalán's assertion, we did not assume identical solvatochromic and thermochromic responses of ttt-DPH to medium changes. Those responses depend on a complex combination of factors that can differ from molecule to molecule.

Designing Hydroxamates and Reversed Hydroxamates to Inhibit Zinc-containing Proteases but not Cytochrome P450s: Insights from Quantum Mechanics and Protein-ligand Crystal Structures.

The Hydroxamate is a useful functional group that binds to metals in a range of enzymes, notably zinc in matrix metalloproteases and histone deacetylases. The group is also able to form interactions with iron leading to inhibition of the cytochromes P450, particularly the 3A4 isoform. We have studied the available crystal structures of zinc-containing proteins bound to hydroxamates and compared the observed geometries with those found by quantum mechanical calculations. This has revealed the likely binding mode preferences for neutral and anionic protonation states and highlighted the importance of electrostatic complementarity. Calculations were also performed for the interaction of the hydroxamate with iron in a heme environment, as found in the cytochromes P450. These reveal that the preferred binding mode of hydroxamates in this environment involves the s-trans conformation. These calculations provide design guidelines for those interested in designing inhibitors of metalloenzymes that do not block metabolism of other drugs. The ability to predict the geometries and energies of binding modes that cannot be studied experimentally is an advantage offered by this kind of study.