Pyrroles from ketoximes and acetylene. 11. Conformation of 1-vinylpyrroles from1H NMR data

A number of 1-vinylpyrroles were studied by PMR spectroscopy. Bulky substituents in the position of the pyrrole ring give rise to deshielding of h_b and a decrease in²J(H_A,H_B) and⁶J(H₃,H_B). The results were interpreted as a decrease in the p, conjugation in the N-vinyl group due to distortion of the coplanarity. The dihedral angle () between the planes of the pyrrole ring and the double bond was estimated (with an accuracy of ±5 °).See [10] for our previous communication [10].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 328–330, March, 1980     

1H and 13C NMR Study of Steric and Electronic Structure of 2-(2-Acylethenyl)-1-vinylpyrroles

According to the ¹H and ¹³C NMR data, the molecule of 2-(2-benzoylethenyl)-1-vinylpyrrole has a nearly planar structure with trans arrangement of the vinyl and oxovinyl groups. The unsaturated fragments give rise to effective conjugation. The vinyl group in 5-substituted 2-(2-acylethenyl)-1-vinylpyrroles strongly deviates from the heteroring plane because of steric effect of the substituent; however, this effect does not change the arrangement of the other unsaturated fragments.     

Structure and dynamics of methyl cis-3,4-diamino-2,3,4,6-tetradeoxy-alpha-L-lyxo-hexopyranoside complexes with PtCl(2) and PdCl(2), by (1)H, (2)H, (13)C, (15)N and (195)Pt NMR spectroscopy in DMSO, CD(3)CN and H(2)O

Pd(ii) and Pt(ii) chloride complexes with LL = methyl cis-3,4-diamino-2,3,4,6-tetradeoxy-alpha-l-lyxo-hexopyranoside of the formulae [Pd(LL)Cl(2)] and [Pt(LL)Cl(2)], , were studied by (1)H, (2)H, (13)C, (15)N and (195)Pt NMR spectroscopy. These techniques were applied for characterization of the structure and ligand exchange dynamics, in case of diastereomeric species formed from in DMSO-d(6), DMSO-h(6) and H(2)O; their general formula was [Pt(LL)XY](+) (X = Cl, Y = DMSO-d(6), ; X = DMSO-d(6), Y = Cl, ; X = Cl, Y = DMSO-h(6), '; X = DMSO-h(6), Y = Cl, '; X = Cl, Y = H(2)O, ; X = H(2)O, Y = Cl, ). Their theoretical structures and NMR parameters, calculated at the level of DFT approach, were also presented and compared to the experimental data. The model complex [Pt(trans-diaminocyclohexane)Cl(2)], , was studied as well. To the best of our knowledge, this work is the first account dealing with the detailed analysis of structure and dynamics of ligand exchange processes in organic solvents and water, performed for a PtCl(2) complex containing a diaminosugar moiety. The kinetic behavior of the studied coordination compounds suggests that some of them may be potentially active in bioassays against cancer cells. Compound exhibits noticeable versatile ligand exchange possibilities in DMSO and H(2)O. Particularly, it undergoes solvolysis in DMSO-d(6), exchanging one chloride atom and yielding two diastereomers and ; the former, being the kinetically favored species, has the DMSO-d(6) ligand syn to the N(3) atom. The lyophilisate of the respective + mixture, earlier equilibrated in DMSO-d(6), after dissolving in H(2)O yields only the latter isomer, which is thermodynamically favored. The solvolysis of in H(2)O yields instantaneously two diastereomeric monoaquated species, and , amounting to 10% of each.     

Automated structure verification based on a combination of 1D (1)H NMR and 2D (1)H - (13)C HSQC spectra

A method for structure validation based on the simultaneous analysis of a 1D (1)H NMR and 2D (1)H - (13)C single-bond correlation spectrum such as HSQC or HMQC is presented here. When compared with the validation of a structure by a 1D (1)H NMR spectrum alone, the advantage of including a 2D HSQC spectrum in structure validation is that it adds not only the information of (13)C shifts, but also which proton shifts they are directly coupled to, and an indication of which methylene protons are diastereotopic. The lack of corresponding peaks in the 2D spectrum that appear in the 1D (1)H spectrum, also gives a clear picture of which protons are attached to heteroatoms. For all these benefits, combined NMR verification was expected and found by all metrics to be superior to validation by 1D (1)H NMR alone. Using multiple real-life data sets of chemical structures and the corresponding 1D and 2D data, it was possible to unambiguously identify at least 90% of the correct structures. As part of this test, challenging incorrect structures, mostly regioisomers, were also matched with each spectrum set. For these incorrect structures, the false positive rate was observed as low as 6%.     

1H NMR spectra of some nitro derivatives of 2-alkylamino-, 2-phenylamino-, 2-piperidyl-, 2-morpholyl-, 2-(N-alkyl-N-nitrosoamino)-, and 2-alkylnitramino-4(or 6)-methylpyridines

¹H NMR spectra of some N-substituted 2-amino-3-nitro-and 2-amino-5-nitropyridines were measured and interpreted. Chemical shift assignments were based on existing chemical shift rules for substituted pyridines and spectral comparison with compounds of similar structure. The splitting of the methyl group signal of the methylamino group into a doublet testifies that the investigated compounds exist, in the amino form. Someortho-amino- andortho-alkylaminonitropicolines were found to give splitting of the amino signals due to intramolecular hydrogen bonding and steric hindrance.Department of Organic Chemistry, Academy of Economics, PL-53 432 Wroclaw, Poland. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 637–642, May, 1997.     

3-(2-对甲苯基乙烯基)-5(4H)-异噁唑酮的合成、晶体结构、1H NMR及其异构化研究

采用甲硫酯与NH2OH·HCl在室温条件下反应,合成了3-(2-对甲苯基乙烯基)-5(4H)-异唑酮,通过单晶X射线衍射确定了产物的结构.由1HNMR确定的构型与晶体结构完全一致,表明标题化合物在弱极性溶剂(如乙醚和氯仿)中是稳定的.半经验AM1和PM3计算的C7和C8净电荷(分别为-0.077,-0.101)可能是H7和H8化学位移(分别为6.83和6.96)很接近的主要原因.B3LYP/6-311G**基组计算的异构体能量数据表明,3-(2-对甲苯基乙烯基)-5(4H)-异唑酮是最稳定的构型     

13C and proton NMR spectra of 2(1H)pyrazinones

¹³C and proton NMR spectra data are given for eleven 2(1H)pyraziones. Assignments of chemical shifts were made by methods which included: deuterium exchange with certain protons of 3-alkyl substituents; change of chemical shifts of certain carbon atoms with change in pH; the use of long-range coupling constants for ¹³C to protons; and various correlations among assigned spectra.     

Sites of hydroxyl radical reaction with amino acids identified by (2)H NMR detection of induced (1)H/(2)H exchange.

Hydroxyl radical reacts with the aliphatic C-H bonds of amino acids by H atom abstraction. Under anaerobic conditions inclusion of a (2)H atom donor results in (1)H/(2)H exchange into these C-H bonds [Goshe et al. Biochemistry 2000, 39, 1761--1770]. The site of (1)H/(2)H exchange can be detected and quantified by (2)H NMR. Integration of the (2)H NMR resonances within a single spectrum permits the relative rate of H atom abstraction from each position to be determined. Analysis of the aliphatic amino acid spectra indicates that the methine and methylene positions were more reactive than the methyl positions. The (2)H NMR spectra of isoleucine and leucine show that H-atom abstraction distal to the alpha-carbon occurs preferentially. Significant (1)H/(2)H exchange was observed into the delta positions of proline and arginine and into the epsilon-methylene of lysine, indicating that a positive charge on a geminal N does not inhibit the (1)H/(2)H exchange. Comparisons of (2)H NMR integrations between amino acid spectra indicated that (1)H/(2)H exchange occurred in the following descending order: L > I > V > R > K > Y > P > H > F >M> T > A > [C, S, D, N, E, Q, G, W]. The extent of (1)H/(2)H exchange into methionine, N-glycyl-methionine, and methionine sulfoxide suggests that a prominent solvent exchange pathway involving hydroxyl radical mediated oxidation of methionine exists to account for the large (2)H incorporation into the gamma-methylene of methionine sulfoxide that is absent for N-glycyl-methionine. Analysis of the (1)H NMR spectra of the reactions with phenylalanine and tyrosine indicated that hydroxyl radical addition to the phenyl ring under the anaerobic reductive reaction conditions did not result in either exchange or hydroxylation.     

Me(2)CuLi*LiCN in diethyl ether prefers a homodimeric core structure [Me(2)CuLi](2) and not a heterodimeric one [Me(2)CuLi*LiCN]: (1)H, (6)Li HOE and (1)H, (1)H NOE studies by NMR

H-Li distances and (1)H-(1)H dipolar interactions in Me(2)CuLiLiCN and Me(2)CuLi in diethyl ether (Et(2)O), obtained by NMR spectroscopy, were used to gain structural information about the contact ion pair of the salt-containing organocuprate Me(2)CuLiLiCN in this solvent. The H-Li distances of Me(2)CuLiLiCN and Me(2)CuLi in Et(2)O, resulting from the initial buildup rates in conjunction with the motional correlation times, are almost identical, indicating a similar homodimeric core structure [Me(2)CuLi](2) for both samples. However, the H-Li distances obtained for Me(2)CuLiLiCN do not rigorously exclude a heterodimeric structure [Me(2)CuLiLiCN] as proposed by ab initio calculations. Therefore, (1)H-(1)H dipolar interactions were investigated by SYM-BREAK-NOE/ROE-HSQC experiments, which allow for the observation of NOEs between equivalent protons. Since these experiments showed similar (1)H-(1)H dipolar interactions of Me(2)CuLiLiCN and Me(2)CuLi, we propose that for Me(2)CuLiLiCN a homodimeric core structure [Me(2)CuLi](2) indeed is predominant in Et(2)O.     

Spatial and Electronic Structure of 2-(2-Furyl)- and 2-(2-Thienyl)pyrroles According to 1H and 13C NMR Data

In 2-(2-furyl)- and 2-(2-thienyl)pyrroles the heterocycles are in efficient ,-conjugation. The presumably possible for this compounds intramolecular hydrogen bond N-H···O or N-H···S is lacking. The COCF₃ group in position 2 of the pyrrole ring is syn-oriented with respect to pyrrole fragment, and the orientation is fixed by an intramolecular hydrogen bond N-H···O. However no bifurcating hydrogen bonds arise in the molecules containing COCF₃ group.     

Spectroscopic studies on methyl torsional behavior in 1-methyl-2(1H)-pyridone, 1-methyl-2(1H)-pyridinimine, and 3-methyl-2(1H)-pyridone. I. Excited state

The laser induced fluorescence excitation and dispersed fluorescence spectra of three nitrogen heterocyclic molecules 1-methyl-2(1H)pyridone (1MPY), 1-methyl-2(1H)pyridinimine (1MPI), and 3-methyl-2(1H)pyridone (3MPY) have been studied under supersonic jet cooled condition. The methyl torsional and some low frequency vibrational transitions in the fluorescence excitation spectrum were assigned for 1MPY. These new assignments modify the potential parameters to the methyl torsion reported earlier. Some striking similarities exist between the torsional and vibrational transitions in the fluorescence excitation spectra of 1MPY and 1MPI. Apart from pure torsional transitions, a progression of vibration-torsion combination bands was observed for both these molecules. The excitation spectrum of 3MPY resembles the spectrum of its parent molecule, 2-pyridone. The barrier height of the methyl torsion in the excited state of 3MPY is highest amongst all these molecules, whereas the barrier in 1MPI is higher than that of 1MPY. To get an insight into the methyl torsional barrier for these molecules, results of the ab initio calculations were compared with the experimental results. It was found that the conformation of the methyl group undergoes a 60 degrees rotation in the excited state in all these molecules with respect to their ground state conformation. This phase shift of the excited state potential is attributed to the pi*-sigma* hyperconjugation between the out-of-plane hydrogen of the methyl group and the molecular frame. It has been inferred that the change in lowest unoccupied molecular orbital energy plays the dominant role in the excited state barrier formation.     

1H and 2H NMR study of chain motion at the poly(dimethylsiloxane)-filler interface

¹H and ²H NMR methods were used to investigate the effect of fillers on the molecular motions in filled poly(dimethylsiloxane). Molecular mobility at the polymer filler interface is strongly different from that outside the adsorption layer. The influence of concentration and type of filler on molecular motions and concentration of the adsorption layer was determined.     

Structure Activity Relationship Studies around DB18, a Potent and Selective Inhibitor of CLK Kinases

Three series of our lead CLK1 inhibitor DB18 have been designed, synthetized and tested against CLKs and DYRK1A kinases. Their cytotoxicity was subsequently measured on seven representative cancer cell lines. Guided by docking experiments, we focused on the less constrained part of the scaffold, and showed that drastically different substituents can be tolerated here. This work ended with the discovery of another promising derivative 12g, with IC₅₀ = 0.004 µM in the inhibition of HsCLK1 and IC₅₀ = 3.94 µM for the inhibition of HsDYRK1A. The SAR results are discussed in the light of extensive molecular modeling analyses. Finally, a kinome scan (463 human kinases) confirmed the outstanding selectivity of our lead compound DB18, suggesting that this scaffold is of prominent interest for selective CLK inhibitors. Altogether, these results pave the way for the development of inhibitors with novel selectivities in this family of kinases.