Genistein complexes with amines. Part II: ab initio study of the complexes with piperazine and triethylamine

The piperazine and triethylamine complexes of genistein, exhibiting high immunosuppressant activity, were ab initio modeled at RHF/6-31G^** level and results were compared with those obtained for genistein–morpholine complexes by X-ray, NMR, and theoretical methods. The most stable genistein–piperazine complex is formed due to hydrogen bonding of genistein's OH group at position C7 to piperazine's nitrogen atom. In the most stable genistein–triethylamine complex genistein's OH group at position C4′ (position para to phenyl substituent) and trimethylamine nitrogen atom are engaged in hydrogen bond formation. The calculations confirmed our previous NMR conclusion that piperazine is more strongly complexed by genistein than is morpholine or triethylamine. The theoretical ¹³C NMR spectra correlate fairly well with the experimental spectra.     

13C CP/MAS NMR studies of vitamin E model compounds

13C cross-polarization magic angle spinning (CP/MAS) NMR data for 2,2,5,7,8-pentamethylchroman-6-ol (2), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox c) (3) and its acetate (4), 2-methoxy-2,2,5,7,8-pentamethylchroman-6-ol (5), 2-hydroxy-2,2,5,7,8-pentamethylchroman-6-ol (6) and 2,2,5,7,8-pentamethylchroman (7) are reported. A deshielding of 7.7 ppm for the carboxylic carbon was observed in solid Trolox due to formation of intermolecular hydrogen bonds within cyclic dimers. Such crystal packing permits effective cross-polarization and fast relaxation (short T1rho(H)). The impact of the proton concentration on the CP dynamics is reflected by the longer T(CP) and T1rhoH for Trolox-d2 (deuterated at mobile proton sites). The calculated GIAO RHF shielding constants are sensitive to intramolecular effects: rotation around the C-6-O bond (changes of sigma up to 8 ppm) and conformation at C-2.     

Reinvestigation to the C-7 Epimerization of Paclitaxel and Related Taxoids Under Basic Conditions

Base-promoted C-7 epimerizations of paclitaxel, 10-deacetylbaccatin III were investigated. It has been found that 13α-OH may play an important role in the equilibrium of C-7 epimers of paclitaxel and related taxoids.     

Spectroscopic analysis of charge transfer complexes between morpholine and iodine.

It has been demonstrated spectroscopically that many nitrogen-containing heterocyclic compounds can form charge transfer complexes with iodine. The complexes of morpholine with iodine were shown to be of the n-sigma type with a 1:1 stoichiometry. A strong donor-acceptor interaction was found (Kc = 1261 +/- 12 mol-1 at 20 degrees C in CCl4), considerably higher than those of complexes of aromatic compounds with iodine. The high value of the formation constant for this complex indicated that morpholine could serve as a starting point for the synthesis of novel anti-thyroid drugs.     

C CP MAS NMR, FTIR, X-ray diffraction and PM3 studies of some N-(ω-carboxyalkyl)morpholine hydrohalides

N-(ω-carboxyalkyl)morpholine hydrochlorides, OC₄H₈N(CH₂)_nCOOH·HCl, n=1–5, were obtained and analyzed by ¹³C cross polarization (CP) magic angle spinning (MAS) NMR, FTIR and PM3 calculations. The structure of N-(3-carboxypropyl)morpholine hydrochloride (n=3) has been solved by X-ray diffraction method at 100 K and refined to the R=0.031. The crystals are monoclinic, space group P2₁/c, a=14.307(3), b=9.879(2), c=7.166(1) Å, β=93.20(3)°, V=1011.3(3) ų, Z=4. In this compound the nitrogen atom is protonated and two molecules form a centrosymmetric dimer, connected by two N⁺–HCl⁻ (3.095(1) Å) and two O–HCl⁻ (3.003(1) Å) hydrogen bonds. ¹³C CP MAS NMR spectra, contrary to the solution, showed non-equivalence of the ring carbon atoms. The PM3 calculations predict a molecular dimer without proton transfer for an HCl complex, while for an HBr complex an ion pairs with proton transfer, and reproduces correctly the conformation of both dimers but overestimates H-bond distances. Shielding constants calculated from the PM3 geometry of ion pairs gave a linear correlation with the ¹³C chemical shifts in solids.     

Synthesis of podophyllotoxin analogues: δ-lactone-containing picropodophyllin, podophyllotoxin and 4′-demethyl-epipodophyllotoxin derivatives

Non-epimerizable cis and trans δ-lactone analogues of podophyllotoxin have been prepared. Thus the synthesis of the cis isomer 4 has been achieved in 8 steps and 4% overall yield from podophyllotoxin 1 via the reduction of the γ lactone ring into the trans diol, selective protection of the 4-OH and 11-OH as a benzylidene acetal, and Wittig elongation at C-13 with inversion of configuration at C-2. Same elongation at C-13 but via the formation of a mesylate and introduction of a cyano group, led to the trans δ-lactone 5 (7 steps from 1 and 6% overall yied) with a small amount of its C-4 epimer 6. The synthesis of non-epimerizable δ-lactone analogues of 4′-demethyl-epipodophyllotoxin 7 and of 4-demethyl podophyllotoxin 8 are also reported. The synthesis of 7 and 8 was based upon the reduction of the γ-lactone ring of 4′-demethyl-4-epipodophyllotoxin followed by selective protection at C-11 and elongation at C-13. (8-15% and 4% overall yields). Compounds 4, 5 and 7 did not display relevant cytotoxicity in vitro against L1210 murine leukemia.     

Stereochemische untersuchungen an C-10-disubstituierten C-9-hydroxyphäophorbiden der a-reihe

The diastereomeric 9-hydroxy pheophorbides 3a, b-1, 2 and 4a, b-1, 2 were prepared by reduction of the 10-alkoxy pheophorbides 1a, b and 2a, b with NaBH₄. Their absolute configuration at C-10 was determined by NMR- and ORD/CD-measurements as well as chemical correlation, the configuration at C-9 by IR- and mainly NMR-spectroscopy. For this purpose, the NMR-spectra of the 9-hydroxy pheophorbides 3a, b-1, 2 had completely to be assigned with the aid of the selectively deuterated alcohols 5a, b-1, 2. The configuration at C-10 is stable under the conditions of the alkaline reduction while C-9 partially epimerizes. The acidic alcoholysis of 3a, b-1, 2, however, proceeds by equilibration at C-10 and almost complete retention at C-9. The H-bonds between the 9-OH group and the C-10 substituents (-COOCH₃, -OCH₃ were investigated by NMR and IR spectroscopy.     

Solid-state acid-base interactions in complexes of heterocyclic bases with dicarboxylic acids: crystallography, hydrogen bond analysis, and 15N NMR spectroscopy

A cancer candidate, compound 1, is a weak base with two heterocyclic basic nitrogens and five hydrogen-bonding functional groups, and is sparingly soluble in water rendering it unsuitable for pharmaceutical development. The crystalline acid-base pairs of 1, collectively termed solid acid-base complexes, provide significant increases in the solubility and bioavailability compared to the free base, 1. Three dicarboxylic acid-base complexes, sesquisuccinate 2, dimalonate 3, and dimaleate 4, show the most favorable physicochemical profiles and are studied in greater detail. The structural analyses of the three complexes using crystal structure and solid-state NMR reveal that the proton-transfer behavior in these organic acid-base complexes vary successively correlating with Delta pKa. As a result, 2 is a neutral complex, 3 is a mixed ionic and zwitterionic complex and 4 is an ionic salt. The addition of the acidic components leads to maximized hydrogen bond interactions forming extended three-dimensional networks. Although structurally similar, the packing arrangements of the three complexes are considerably different due to the presence of multiple functional groups and the flexible backbone of 1. The findings in this study provide insight into the structural characteristics of complexes involving heterocyclic bases and carboxylic acids, and demonstrate that X-ray crystallography and 15N solid-state NMR are truly complementary in elucidating hydrogen bonding interactions and the degree of proton transfer of these complexes.     

The efficiency of C-4 substituents in activating the beta-lactam scaffold towards serine proteases and hydroxide ion

The presence of a leaving group at C-4 of monobactams is usually considered to be a requirement for mechanism-based inhibition of human leukocyte elastase by these acylating agents. We report that second-order rate constants for the alkaline hydrolysis and elastase inactivation by N-carbamoyl monobactams are independent of the pKa of the leaving group at C-4. Indeed, the effect exerted by these substituents is purely inductive: electron-withdrawing substituents at C-4 of N-carbamoyl-3,3-diethylmonobactams increase the rate of alkaline hydrolysis and elastase inactivation, with Hammett pI values of 3.4 and 2.5, respectively, which indicate the development of a negative charge in the transition-states. The difference in magnitude between these pI values is consistent with an earlier transition-state for the enzymatic reaction when compared with that for the chemical process. These results suggest that the rate-limiting step in elastase inactivation is the formation of the tetrahedral intermediate, and that beta-lactam ring-opening is not concerted with the departure of a leaving group from C-4. Monobactam sulfones emerged as potent elastase inhibitors even when the ethyl groups at C-3, required for interaction with the primary recognition site, are absent. For one such compound, a 1 : 1 enzyme-inhibitor complex involving porcine pancreatic elastase has been examined by X-ray crystallography and shown to result from serine acylation and sulfinate departure from the beta-lactam C-4.     

Hydrogen bonding structure and stability of alpha-chitin studied by 13C solid-state NMR

The structure and stability of hydrogen bonds in alpha-chitin were investigated by (13)C solid-state NMR measurements at different temperatures. Splitting of the carbonyl carbon signal for alpha-chitin was interpreted as two types of hydrogen bonding; the peaks at 173.5 and 175.8 ppm were assigned, respectively, to a carbonyl carbon hydrogen bonded exclusively to the NH group and a carbonyl carbon hydrogen-bonded to both NH and C(6)-OH groups. Approximately 60% of carbonyl groups exclusively contributed to the intermolecular hydrogen bonding and ca. 40% of them to the combination of intermolecular and intramolecular hydrogen bonding. Internal rotation around the C(5)-C(6) bond was detected at 55 degrees C.     

PFOS在锐钛型TiO2表面吸附行为的理论研究

采用密度泛函理论(DFT)B3LYP方法对全氟辛烷磺酸(PFOS)在锐钛型TiO2表面的化学吸附和物理吸附行为进行了研究,其中化学吸附包含双齿双核(BB)和单齿单核(MM)在内的4种可能的吸附构型.吸附能(Eads)及反应吉布斯自由能(ΔGads)的计算结果表明,PFOS分子易于与TiO2表面发生氢键作用吸附;化学吸附表现为PFOS分子与TiO2表面的水分子(H2O)和羟基(—OH)反应,且与取代—OH相比,H2O取代相对更容易发生,其中,MM1构型(取代一个表面水分子)为化学吸附中的优势构型.PFOS在锐钛矿表面吸附的热力学稳定性和反应自发性顺序如下:H-Bonded(氢键吸附)>MM1(取代一个表面水分子)>BB1(取代两个表面水分子)>MM2(取代一个表面羟基)>BB2(取代一个表面水分子和一个表面羟基).成键结构分析表明,TiO2表面H2O/—OH官能团与PFOS上的磺酸基之间形成了中等强度的氢键;在化学吸附过程中,电荷从PFOS分子向TiO2表面发生转移,生成Ti—O—S化学键,电荷转移主要来自PFOS分子的O和F原子.     

Ni(Ii)-Catalysed Reactions of Free D-Fructose Derivatives Modified at Positions C-5 and/or C-6

Abstract

The nickel(II) catalysed isomerisation reactions of D-fructose derivatives modified at positions 5 and/or 6 were investigated. 5,6-Dimodified open-chain D-fructose derivatives as well as an open-chain derivative of D-xylulose reacted to give complex mixtures containing no major product. 5-Modified ketohexoses invariantly were degraded to the corresponding methyl pentonates upon loss of C-1. 6-Modified D-fructofuranose furnished the desired rearrangement into a branched-chain derivative of D-ribose. In marked contrast to previous belief, from these results it appears that 5-OH plays an important role in the productive co-ordination of the D-fructose derivatives to the nickel-ethylenediamine complexes under consideration.     

Beta-alanine-hydrochloride (2:1) crystal: structure, 13C NMR and vibrational properties,protonation character

The crystal structure of beta-alanine-hydrochloride (2:1) complex (2A-HCl) has been determined by X-ray diffraction method at 298 and 100 K as monoclinic, space group C2/c, Z=4. The crystal comprises chloride anions and protonated beta-alanine dimers: two beta-alanine zwitterions are joined by strong, symmetric (Ci) hydrogen bond with the O...O distance of 2.473 A at room temperature. Powder FT-IR and FT-Raman as well as solid state 13C NMR spectra provide insights into the solid structure of this complex, character of its hydrogen bonds and the beta-alanine protonation.     

The 1:2 Complex of Piperazine with Some Phenols:Hydrogen Bonding Pattern Involved in Transition States in Solution

Previous calorimetric and iR studiesl had showed that, in a system of secondary amineand unhindered phenol, hydrogen bonds of O--H---N and N--H---O concurred toappear. Fast proton exchange between proton donor and acceptor in solution is usualphenomenon 2-". Therefore, a novel model (Scheme l) for the I fZ complex of piperazine(Pip) respectively with phenol (Ph), 2-metylphenol (O-MPh), 4-metylphenol (P-MPh)(abbreviated generally as PiP' ZXPh) in solution is now established. As showed …     

Conformational and tautomeric eccentricities of 2-acetyl-1,8-dihydroxynaphthalenes

Tautomerism in aromatic systems with oxygen substitutents is rare. This is investigated in 2-acetyl-1,8-dihydroxy-3,6-dimethylnaphthalene (1) and in 2,7-diacetyl-1,8-dihydroxy-3,6-dimethylnaphthalene (2). The tautomeric nature of 2-acetyl-1,8-dihydroxy-3,6-dimethylnaphthalene is supported by long-range hydrogen-hydrogen coupling between the OH-1 and the OH-8 and by the isotope effects on 13C caused by deuteration at the CH3C==O methyl group. Compound 2 participates in a degenerate equilibrium between two equivalent nonsymmetrical rotamers (2A and 2B), each having two intramolecular O...HO hydrogen bonds: one involving an acetyl oxygen and the neighboring hydroxyl group, and the other between the oxygen centers at positions 1 and 8. In addition, each rotamer is involved in a tautomeric equilibrium, with a structure having an OH-substituted exocyclic double bond (2AT or 2BT).DFT calculations for a large set of compounds highlight the factors controlling the unusual rotational and tautomeric behaviors. A very important factor seems to be the repulsive interaction between the O-1 and O-8 centers, which is modulated by formation of an OH-1...O-8 or OH-8...O1 hydrogen bond. Steric interactions, mesomeric release of electrons from the oxygen at position 8, and a strong OH...O...C hydrogen bond are other factors.Solid-state 13C NMR spectra of 2,7-diacetyl-1,8-dihydroxy-3,6-dimethylnaphthalene at different temperatures demonstrated no averaging in the solid, whereas partially deuterated 2-acetyl-1,8-dihydroxy-3,6-dimethylnaphthalene showed an isotope effect at C-1 of 1.5 ppm, indicating tautomerism in the solid state.     

Absolute stereochemistry of amphidinolide C: synthesis of C-1-C-10 and C-17-C-29 segments

Two of each diastereomers of the C-1-C-10 and C-17-C-29 segments of amphidinolide C (1) were synthesized. Comparing the ¹H NMR chemical shifts of its MTPA esters with those of linear methyl ester of 1, the absolute configurations at C-7, C-8, C-20, C-23, and C-24 in amphidinolide C (1) were confirmed to be all R.     

Spectroscopic Studies of a Water-soluble Derivative of Hypocrellin A and Its One- and Two-Electron Reduction Products

In this study the spectroscopic characteristics of a water-soluble derivative of hypocrellin A (HA), 14-dehydroxy-15-deacetyl-hypocrellin A-13-sulfonate(13-SO3Na-DDHA),and its one- and two-electron reduction products have been investigated. From the changes in absorbance with pH it was observed that the two phenolic hydroxy groups at C-3 and C-10 positions of 13-SO3Na-DDHA or HA dissociated stepwise with increase of pH values. The pKa values for 13-SO3Na-DDHA and HA were determined using an effective method established in this study. Attempts were also made to use absorption and ESR spectroscopies to study the photoreduction of 13-SO3Na-DDHA. It was found that 13-SO3Na-DDHA was directly reduced to its two-electron reduction product in buffered aqueous solution (pH 7. 7). However, in DMF-buffer (1 :1/ v : v,pH 7. 7), it proceeded with one-electron reduction to generate its semiquinone radical anions. The semiquinone radical anions decayed according to second-order kinetics. indicating that the terminatio     

13C-13C NOESY: an attractive alternative for studying large macromolecules

13C direct detection provides a valuable alternative to 1H detection to overcome fast relaxation because of its smaller magnetic moment. 13C-13C NOESY spectra were acquired for a dimeric protein of molecular mass 32 000 and for a monomeric analogue. With increasing molecular mass, the quality of 13C-13C NOESY spectra improves while the scalar-based experiments become less sensitive, as predicted by the increase in the molecular mass. 13C-13C NOESY spectra of the dimer were acquired with different mixing times. The mixing time can be tuned to detect mainly one-bond correlations, or it can be increased to also detect correlations between nuclei at longer distances. It is proposed that 13C-13C dipolar-based experiments provide a promising tool for signal detection and assignment in large macromolecules, such as multimeric species and macromolecular complexes, for which scalar-based experiments become less effective.     

Theoretical study on the factors controlling the stability of the borate complexes of ribose, arabinose, lyxose, and xylose

Recent experimental studies suggest that complexation with borate minerals stabilizes ribose, and that the borate complex of ribose is more stable than those of related aldopentoses, that is, arabinose, lyxose, and xylose. These findings have revived the debate on the plausibility of the RNA-world theory, because they provide an explanation for the stabilization and selection of ribose in prebiotic conditions. In this paper we unravel the factors that make the ribose-borate complex the most stable one. For this purpose, we have investigated the structure and stability of the ribose-, arabinose-, lyxose-, and xylose-borate complexes using density functional theory and a continuum solvent approach. The computed results reveal that in the aldopentose-borate complexes, the electrostatic field of the borate is strong enough to change the orientation of the nearby hydroxyl groups compared to noncomplexed aldopentoses. In addition, we show that the distinct stability of the ribose-borate 2:1 complex can be attributed to 1) a strong hydrogen bond between the ribose 3-OH and one of the negatively charged borate oxygen atoms, and 2) a favorable contact between the aqueous medium and the 5-CH(2)OH group due to the space separation between the 5-CH(2)OH group and the borate anion.     

Carbon-13 NMR spectra of nucleoside 3′,5′-cyclic phosphates. Proposition for revised signal assignments

On the basis of the data obtained from ¹³C NMR spectra of 8,2′-S-cycloadenosine 3′,5′-cyclic phosphate and other nucleoside 3′,5′-cyclic phosphate analogues, it is suggested that the published assignments of the C-3′ and C-4′ signals in nucleoside 3′,5′-cyclic phosphates should be reversed. According to the revised assignments, C-4′, which is fixed very closely to the diesterified phosphate group is markedly shielded (?12.5 to ?15 ppm), and the C-3′ signal shows a downfield shift (+6 to +8 ppm) which is comparable to that for the C-5′ signal, for all compounds so far measured when compared with the chemical shifts for the corresponding nucleosides. The 3′,5′-cyclic phosphates of thymidine and 8,2′-S-cycloadenosine, which have no α-OH group on C-2′, show similar chemical shift changes for the corresponding sugar carbons which are different from those observed for ribonucleoside derivatives.