Electronic and steric substituent effects on the fluorescence emission of 2-pyrazoline derivatives

A series of substituted 2-pyrazolines were synthesized, and the steric and electronic effects of substituents on the C₃- and C₅-positions of the heterocyclic ring on their fluorescent ability were investigated. Two different conjugative intramolecular charge transfer (ICT) and intramolecular charge transfer through space (spiro-conjugation) affect the fluorescence intensity of these compounds. The extent of the ICT process and spiro-conjugation depends on the electronic nature of the additional substitution and its position on the attached aryl rings. In addition, the effects of the concentration and the solvent polarity on the fluorescence emission were studied. Density functional theory (DFT) calculations were carried out to gain insight into the geometric, electronic, and spectroscopic properties of the pyrazoline derivatives. The results of both experimental and computational studies explain the effects of the geometrical orientation of the C₃- and C₅-aryl rings toward the heterocyclic ring and also the electronic nature of their additional substitutions on the fluorescence intensity.     

Studies on electronic structures and related properties of [Ru(bpy)2(dpq)] and its 9,9′-substituted derivates with DFT method

Studies on electronic structures and related properties of [Ru(bpy)₂(dpq)]²⁺ and its 9,9′-substituted derivates are carried out using DFT method at B3LYP/LanL2DZ level. The substituent effects caused by the electron-pushing group (OH) and the electron-withdrawing groups (F) on the electronic structures and its related properties, e.g. the energies and components of some frontier molecular orbitals, the spectral properties, and the net charge populations of some main atoms of the complexes, etc. have been investigated. The computational results show that: first, the substituents have some important effects on the first excited state properties. Both electron-withdrawing group (F) and the electron-pushing group (OH) can all activate the main ligand and passivate the co-ligands in the first excited states of [Ru(bpy)₂(9,9′-2R-dpq)]²⁺, and both can lead to a little red shift in the electronic ground bands of the substitutive derivates, respectively, in particular, the electron-pushing group (OH) can lead to that more. Secondly, the most negative charges are populated on N1 or N5, and the next most negative charges are populated on C8 among all atoms of aromatic ring skeleton. In addition, the substituents have slight effects on coordination-bond lengths of complexes. The above theoretical results should be important to further inquire into the interaction mechanism between the complexes and DNA active units from the interactions between molecular orbitals, or from the interactions between atomic charges.     

Synthesis and structures of aryl-substituted tetramethylcyclopentadienyl dinuclear metal carbonyl complexes

A series of 14 aryl-substituted tetramethylcyclopentadienyl dinuclear metal carbonyl complexes have been synthesized by treating the corresponding ligands (C₅Me₄C₆H₄X-4) (X = H, Me, Cl, OMe) with Ru₃(CO)₁₂, Fe(CO)₅, or Mo(CO)₃(MeCN)₃, respectively in refluxing xylene. It showed that the electronic effects of the substituents had influence on the molecular structures and reactions of the complexes, especially for the ruthenium and molybdenum complexes. In the reactions of aryl-substituted tetramethylcyclopentadiene with Mo(CO)₃(MeCN)₃, the electron-withdrawing effect of the substituent in the para position of benzene ring is favorable to produce the Mo-Mo triple bonded complexes, but the electron-donor effect of the substituent in the para position of benzene ring is favorable to produce the Mo-Mo single bonded complexes. In a given condition, the Mo-Mo single bonded complex could be transformed into the corresponding Mo-Mo triple bonded complex. The structures of nine complexes were determined by single crystal X-ray diffraction.     

Flexibility of the pyranose ring in α- and β-D-glucoses

Conformational energies of α- and β-D -glucopyranoses were computed by varying all the ring bond angles and torsional angles using semiempirical potential functions. Solvent accessibility calculations were also performed to obtain a measure of solvent interaction. The results indicate that the ⁴C₁ (D ) chair is the most favored conformation, both by potential energy and solvent accessibility criteria. The ⁴C₁ (D ) chair conformation is also found to be somewhat flexible, being able to accommodate variations up to 10° in the ring torsional angles without appreciable change in energy. Observed solid-state conformations of these sugars and their derivatives lie in the minimum-energy region, suggesting that the substituents and crystal field forces play a minor role in influencing the pyranose ring conformation. Theory also predicts the variations in the ring torsional angles, i.e., CCCC < CCCO < CCOC, in agreement with the experimental results. The boat and twist-boat conformations are found to be at least 5 kcal mol^?1 higher in energy compared to the ⁴C₁ (D ) chair, suggesting that these forms are unlikely to be present in a polysaccharide chain. The ¹C₄ (D ) chair has energy intermediate between that of the ⁴C₁ (D ) chair and that of the twist-boat conformation. The calculated energy barrier between ⁴C₁ (D ) and ¹C₄ (D ) conformations is high—about 11 kcal mol^?1.     

Developmental Histology of Organogenic and Embryogenic Tissue in Picea omorika Culture

Newly synthesized derivatives of α-aminoalkanephosphonic acids (aminophosphonates) differ in the substituents at the carbon, nitrogen, and phosphorus atoms. They modified in different degree the properties of cucumber (Cucumis sativus cv. Wisconsin) cotyledon membranes, physiological activity of some enzymes (guaiacol and pyrogallol peroxidases, and catalase), chlorophyll content, and cellular membrane lipid peroxidation. Most active modifiers were those possessing sufficiently long hydrocarbon substituents at the nitrogen atom (C₁₀H₂₁) or isopropyl chain at the phosphorus atom. The branched tertbutyl group at the carbon atom enhanced slightly the activities of peroxidases in contrast to hexane ring at the same position, which decreased them. This revised version was published online in July 2006 with corrections to the Cover Date.     

Symmetry breaking in charge-transfer compounds. The effects of electric fields and substituents on the properties of bipyrazine cations

The effects of an electric field and of various substituents on the symmetry breaking of degenerate near-midgap orbitals and on different properties in bi-N,N-pyrazine-1,6-hexatriene dications ([C₄N₂H₄—(CH)₆—C₄N₂H₄]²⁺) are investigated by means of semiempirical PM3 and INDO CI methods. The electric field is simulated by applying positive/negative point charges at varying distances from the end-points, and the substitutions are done with single chlorine atoms or with CN, OH or CH₃ groups, at various positions along the chain or on one of the pyrazine rings. The results are compared with calculations on the unsubstituted, field-free system. It is found that an electric field (e.g., as applied over a membrane) leads to significant symmetry breaking and also polarizes the HOMO and LUMO, such that electron transfer between these orbitals generates large dipole-moment shifts and non-negligible oscillator strengths. With substituents, no major symmetry breaking is observed for the ground state. Instead, strong modifications of the orbital picture are observed, in particular when using the stronger electron-withdrawing substituents. Placing the substituent in a ring position does, furthermore, lead to the possibility of large charge transfer.     

X-ray crystal,and molecular,structure of 1,2,3-tri-O-acetyl-4,5-dideoxy-4-C-[(R)-phenylphosphinyl]-α-l-lyxofuranose: The first x-ray analysis of a pentofuranose having phosphorus in the hemiacetal ring

X-Ray crystallographic analysis was performed on the compound to which had been assigned the structure of 1,2,3-tri-O-acetyl-4,5-dideoxy-4-C-[(R)-phenylphosphinyl]-α-l-lyxofuranose. The results showed that the compound has the proposed configuration, the five-membered ring is in the E₃ conformation, with a tendency towards the ³T₂ form, the substituents at P-5 and C-5 are linked bisectionally, the acetoxyl group at C-2 and the methyl group at C-4 are linked quasiequatorially, and the acetoxyl group at C-3 is linked axially.     

Structural studies on santalin permethyl ether

The chloroform extract of the heartwood of Pterocarpus santalinus yielded a mixture of red pigments which could be separated by polyamide column chromatography into two major compounds, santalin-A and santalin-B. Both gave the same permethyl ether, C₃₈H₃₆O₁₀ which had 8 methoxyls and formed a number of derivatives typical of anhydrobenzopyranols. IR and UV spectra confirmed the same. NMR and MS suggested the presence of homoveratrayl group supported by the formation of veratraldehyde in alkali degradation. Permanganate oxidation gave 2,4-dimethoxy benzoic acid, veratric acid and 3,4,6-trimethoxy phthalic acid. On a basic fluorone skeleton, the substituents in the A ring are indicated by 2,4-dihydroxy-5-methoxy benzaldehyde, an alkali fission product and, further, 2,4-dimethoxy phenyl and homoveratryl units are located in ring C based on NMR, MS and biogenetic considerations. The residues constitute another benzene ring fused to ring C leading to the complete structures of the permethyl ether as (VII) which explains all its degradations and which constitutes a highly condensed biflavonoid of a new type.     

Effects of imidazolium room temperature ionic liquids on the fluorescent properties of norfloxacin

The effects of 12 imidazolium room temperature ionic liquids (RTILs), including [C_nmim]BF₄, [C_nmim]PF₆, and [C_nmim]Br (n = 4, 6, 8, 10), on the fluorescent properties of norfloxacin were examined. The fluorescence intensity of norfloxacin at 0.1 mg/L in methanol significantly increased with the addition of [C_nmim]BF₄ and [C_nmim]PF₆ into the solvent at 0.1–15.0%. The sensitizing effect may result from the higher viscosity of the RTILs–methanol mixture solvent than that of the methanol itself. However, the quenching effect on fluorescence of norfloxacin was observed in [C_nmim]Br–methanol solvent. The fluorescence intensities of norfloxacin decreased with an increase in the alkyl chain length of the alkyl substituents of the imidazolium ring of RTILs. The main interaction between the RTILs and norfloxacin is not by hydrogen bonding. The fact, that some RTILs can significantly sensitize fluorescence of norfloxacin, indicates that RTILs could be a group of promising solvents for development of sensitive spectrofluorimetric methods for determination of norfloxacin at ultra‐trace levels in environmental samples. Copyright © 2011 John Wiley & Sons, Ltd.     

Analysis of the structure of the flavin-binding sites of flavocytochrome P450 BM3 using surface enhanced resonance Raman scattering

Flavocytochrome P450 BM3, an FMN-deficient mutant (G570 D), the component reductase and an FAD-containing domain were studied using surface enhanced resonance Raman scattering (SERRS). They were compared to spectra obtained from the free flavins FAD and FMN. For the holoenzyme and reductase domain, FMN is displaced during SERRS analysis. However, studies with the G570 D mutant indicate that FAD is retained in its active site. Analysis of SERRS frequencies and intensities provides information on the nature of the flavin binding site and the planarity of the ring, and enables an interpretation of the hydrogen bonding environment around ring III of the isoalloxazine moiety. Hydrogen bonding is strong at N₃–H, C₂=O and C₄=O, but weak at N₅. Structural alteration of the FAD domain of P450 BM3 is caused by removal of the FMN-binding domain. Further, the hydrogen bond at N₃–H is lost and that at C₂=O is weakened and the isoalloxazine ring system in the FAD domain appears to adopt a more planar arrangement. Alterations in the environment of the FAD in its isolated domain are likely to relate to changes in the redox properties and suggest a close structural interplay of FAD with the FMN-binding domain in intact flavocytochrome P450 BM3. Received: 5 August 1998 / Revised version: 11 February 1999 / Accepted: 15 February 1999     

X-ray crystal, and molecular, structure of 1,2,3-tri-O-acetyl-4,5-dideoxy-4-C-[(R)-phenylphosphinyl]-α- -lyxofuranose: The first x-ray analysis of a pentofuranose having phosphorus in the hemiacetal ring

X-Ray crystallographic analysis was performed on the compound to which had been assigned the structure of 1,2,3-tri-O-acetyl-4,5-dideoxy-4-C-[(R)-phenylphosphinyl]-α- -lyxofuranose. The results showed that the compound has the proposed configuration, the five-membered ring is in the E₃ conformation, with a tendency towards the ³T₂ form, the substituents at P-5 and C-5 are linked bisectionally, the acetoxyl group at C-2 and the methyl group at C-4 are linked quasiequatorially, and the acetoxyl group at C-3 is linked axially.     

A DFT study of addition reaction between fragment ion (CH<Subscript>2</Subscript>) units and fullerene (C<Subscript>60</Subscript>) molecule

The theoretical study of the interaction between CH₂ and fullerene (C₆₀) suggests the existence of an addition reaction mechanism; this feature is studied by applying an analysis of electronic properties. Several different effects are evident in this interaction as a consequence of the particular electronic transfer which occurs during the procedure. The addition or insertion of the methylene group results in a process, where the inclusion of CH₂ into a fullerene bond produces the formation of several geometric deformations. A simulation of these procedures was carried out, taking advantage of the dynamic semi-classical Born-Oppenheimer approximation. Dynamic aspects were analyzed at different speeds, for the interaction between the CH₂ group and the two bonds: CC (6, 6) and CC (6, 5) respectively on the fullerene (C₆₀) rings. All calculations which involved electrons employed DFT as well as exchange and functional correlation. The results indicate a tendency for the CH₂ fragment to attack the CC (6, 5) bond.     

Design,synthesis and biological evaluation of potential antibacterial butyrolactones

Novel butyrolactone analogues were designed and synthesized based on the known lichen antibacterial compounds, lichesterinic acids (B-10 and B-11), by substituting different functional groups on the butyrolactone ring trying to enhance its activity. All synthesized butyrolactone analogues were evaluated for their in vitro antibacterial activity against Streptococcus gordonii. Among the derivatives, B-12 and B-13 had the lowest MIC of 9.38 μg/mL where they have shown to be stronger bactericidals, by 2–3 times, than the reference antibiotic, doxycycline. These two compounds were then checked for their cytotoxicity against human gingival epithelial cell lines, Ca9–22, and macrophages, THP-1, by MTT and LDH assays which confirmed their safety against the tested cell lines. A preliminary study of the structure–activity relationships unveiled that the functional groups at the C₄ position had an important influence on the antibacterial activity. An optimum length of the alkyl chain at the C₅ position registered the best antibacterial inhibitory activity however as its length increased the bactericidal effect increased as well. This efficiency was attained by a carboxyl group substitution at the C₄ position indicating the important dual role contributed by these two substituents which might be involved in their mechanism of action.     

The effect of some alkyl derivatives of cholesterol on the permeability properties and microviscosities of model membranes

The properties of lecithin liposomes or vesicles containing a variety of sterols have been studied by measuring either the release of entrapped glucose or determining microviscosity by fluorescence depolarization of the probe diphenylhexatriene. Sterols containing alkyl substituents at C₃, C₄, or C₁₄ were less effective in reducing glucose permeability or increasing microviscosity than cholesterol. 19-Norcholesterol was also less effective than cholesterol in raising membrane viscosity. These results support the hypothesis that the selective biological demethylation of lanosterol to a planar (α-face) structure optimizes the ability of the sterol molecule to condense the lipid phase of the membrane bilayer. Removal of an angular methyl group (C₁₉), a rare event in biological systems, has the opposite effect.     

Proton magnetic resonance studies of the conformational changes of dideoxynucleoside ethyl phosphotriesters

PMR investigations on the diastereomeric phosphate methyl protons of the dinucleoside ethyl phosphotriesters Tp(C₂H₅)T, dA, and dIp(C₂H₅)dI have been used to study the conformational changes of these dimersin solution. In D₂O (273°K), the diastereomeric phosphate-methly groups of Tp(C₂H₅)T appear as a triplet. The methyl resonances of dIp(C₂H₅)dI and dAp(C₂H₅)dA appear as two sets of triplets and their chemical shift differences (δ₁ ? δ₂), decrease with increasing temperature, finally becoming zero at 292°K and 333°K, respectively. The same phenomenon is observed for dAp(C₂H₅)dA in CD₃OD; in this detacking solvent, the difference (δ₁ ? δ₂) diminishes to zero at a lower temperature (261°K). At room temperature in D₂O, the chemical shift of the phosphate methyl of Tp(C₂H₅)T appears at lower field than those of dIp(C₂H₅)dI or dAp(C₂H₅)dA. The differences between the chemical shifts of these groups (δ_I ? δ_T or δ_A ? δ_T) increase with increasing temperature, and reach maximal values at 301°K and 333°K, respectively. The results suggest that at low temperature the largest fraction of the dimer population exists in a stacked state, with the phosphate-ethyl groups outside the stack. Increasing temperature causes an oscillation of the bases and a shift in the dimer population away from the stacked state. Finally at high temperature, the planar bases rorate with respect to one another and in the case of dIp(C₂H₅)dI and dAp(C₂H₅)dA, the ethyl groups experience shielding by the anisotropic ring current of the five-membered ring of the bases. Thus, the current pmr studies and those reported earlier from our laboratory support an “oscillation-rotation model” for the unstacking process of the dimers. The relationship of this model and the “two-state model” is discussed.     

High resolution nuclear magnetic resonance spectroscopy of glycosphingolipids. I: 360 MHz 1H and 90.5 MHz 13C NMR analysis of galactosylceramides

The high resolution ¹H and ¹³C nuclear magnetic resonance (NMR) spectra of galactosylceramides containing n-fatty acids and α-hydroxy fatty acids were recorded in dimethylsulfoxide solution with and without addition of D₂O. From the coupling constants of the sugar ring protons, a ⁴C₁ conformation can be deduced. In contrast to the conformation in aqueous solution, the C⁶ hydroxymethylene group is freely rotating around the C⁶C⁵ bond. In the ceramide residue all signals produced by protons linked to carbons bearing electronegative substituents could be attributed. The large difference in coupling constants of the methylene protons of C^1′ to the C^2′ methine proton of the sphingosine indicates a restricted rotation around the C^1′C^2′ bond. The assignments of the hydroxy and amino protons follow from the decoupling of the corresponding methine protons.     

5-Halogenopyrimidines

Microbial enzymatic hydroxylation of 4-hydroxy-5-halogeno-pyrimidines was shown to take place at the C₂ of the pyrimidine ring, giving rise to corresponding 5-halogeno-uracils. The analogous 2-hydroxy-5-fluoropyridine was never hydroxylated by microorganisms at the C₄ to give rise to 5-fluorouracil. An inhibitory effect was found only with 4-hydroxy-5-fluoropyrimidine (the starting substance) and its transformation metabolite (5-fluorouracil). In this case the metabolite formed possessed a greater inhibitory effect than did the original pyrimidine derivative.     

The scope of thallium nitrate oxidative cyclization of chalcones; synthesis and evaluation of isoflavone and aurone analogs for their inhibitory activity against interleukin-5

The oxidative cyclization of 2′-hydroxy-6′-cyclohexylmethoxychalcones 5 using thallium (III) nitrate (TTN) in alcoholic solvents produced isoflavones 2 and (or) aurones 3 depending on the electronic nature of p-substituents on ring B. Chalcones with strong electron donating substituents (OH, OCH₃) were exclusively converted to isoflavones 2. Chalcone with weak electron donating substituents (CH₂CH₃) was transformed into isoflavone 2 and the aurone 3 in approximate ratio 1:1. Chalcones with hydrogen or electron withdrawing substituents (Cl, CHO, COOCH₃, and NO₂) formed aurones 3. Synthesized isoflavones 2 and aurones 3 were evaluated for their inhibitory activity against interleukin-5. Among them, 5-(cyclohexylmethoxy)-3-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (2h, >100% inhibition at 50 μM, IC₅₀ = 6.1 μM) gave most potent activity. All the aurones 3 were inactive.