Effect Of Substitution Pattern Research Articles

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions.

Redox active phenotellurazine catalysts have been recently utilized in two different cross-dehydrogenative coupling reactions. In this study, we revisit the design of the phenotellurazine redox catalysts. In particular, we investigate the level of cooperativity between the Te- and N-centers, the effect of secondary versus tertiary N-centers, the effect of heterocyclic versus non-heterocyclic structures, and the effect of substitution patterns on the redox catalytic activity.

Synthesis and HPLC-ECD Study of Cytostatic Condensed O,N-Heterocycles Obtained from 3-Aminoflavanones.

Racemic chiral O,N-heterocycles containing 2-arylchroman or 2-aryl-2H-chromene subunit condensed with morpholine, thiazole, or pyrrole moieties at the C-3-C-4 bond were synthesized with various substitution patterns of the aryl group by the cyclization of cis- or trans-3-aminoflavanone analogues. The 3-aminoflavanone precursors were obtained in a Neber rearrangement of oxime tosylates of flavanones, which provided the trans diastereomer as the major product and enabled the isolation of both the cis- and trans-diastereomers. The cis- and trans-aminoflavanones were utilized to prepare three diastereomers of 5-aryl-chromeno[4,3-b][1,4]oxazines. Antiproliferative activity of the condensed heterocycles and precursors was evaluated against A2780 and WM35 cancer cell lines. For a 3-(N-chloroacetylamino)-flavan-4-ol derivative, showing structural analogy with acyclic acid ceramidase inhibitors, 0.15 μM, 3.50 μM, and 6.06 μM IC50 values were measured against A2780, WM35, and HaCat cell lines, and apoptotic mechanism was confirmed. Low micromolar IC50 values down to 2.14 μM were identified for the thiazole- and pyrrole-condensed 2H-chromene derivatives. Enantiomers of the condensed heterocycles were separated by HPLC using chiral stationary phase, HPLC-ECD spectra were recorded and TDDFT-ECD calculations were performed to determine the absolute configuration and solution conformation. Characteristic ECD transitions of the separated enantiomers were correlated with the absolute configuration and effect of substitution pattern on the HPLC elution order was determined.

Effects of Substitution Pattern in Phosphite Ligands Used in Rhodium-Catalyzed Hydroformylation on Reactivity and Hydrolysis Stability

The stability of homogeneous catalytic systems is an industrially crucial topic, which, however, receives comparatively little attention from academic research. Phosphites are among the most frequently used ligands in industrial, rhodium-catalyzed n-regioselective hydroformylation. However, they are particularly vulnerable to hydrolysis. Since the decomposition of ligands should be dependent on the substitution patterns, phenyl, tert-butyl and condensed ring systems of benzopinacolphosphites were evaluated concerning their activity, regioselectivity and hydrolysis stability. A series of twelve strongly related phosphites were synthesized, tested in the hydroformylation of isomeric n-octenes, and studied in hydrolysis experiments using in situ NMR spectroscopy. Our results show that substituents in the ortho-position, especially tert-butyl substituents, enhance hydrolysis stability while maintaining compelling activity and regioselectivity. In contrast, substituents in the para-position may destabilize the phosphite.

The Effect of Substitution Pattern on Binding Ability in Regioisomeric Ion Pair Receptors Based on an Aminobenzoic Platform.

A series of ditopic ion pair receptors equipped with 4-nitrophenylurea and 1-aza-18-crown-6-ether linked by ortho-(1), meta-(2), and para-(3) substituted benzoic acid were readily synthesized in three steps from commercially available materials. The binding properties of these regioisomeric receptors were determined using UV-vis and 1H NMR spectroscopy in MeCN and in the solid state by single-crystal X-ray diffraction crystallography. The solution studies revealed that, apart from carboxylates, all the anions tested formed stronger complexes in the presence of sodium cations. Receptors 2 and 3 were found to interact with ion pairs with remarkably higher affinity than ortho-substituted 1. 1H NMR titration experiments showed that both urea NH protons interacted with anions with comparable strength in the case of receptors 2 and 3, but only one of the NHs was effective in anion binding in the case of receptor 1. X-ray analysis of the crystal structure of receptor 1 and 1·NaPF6 complex showed that binding was hampered due to the formation of an intramolecular hydrogen bond. Analysis of the crystal structures of 2·NaBr and 3·NaBr complexes revealed that proper mutual orientation of binding domains was responsible for the improved binding of the sodium salts.

Changing up BN-Polystyrene: Effect of Substitution Pattern on the Free-Radical Polymerization and Polymer Properties

Azaborinine-substituted polymers are poised to dramatically expand the diversity and functionality of polystyrenes via BN for CC substitution, but this new class of materials remains underexplored....

Effect of regioisomerism on the self-assembly, photophysical and gelation behavior of aroylhydrazone based polycatenars: Synthesis and characterization

In this paper we report five series of aroylhydrazone based polycatenars differing from each other in number and position of alkoxy chains on one end of the core; keeping other end the same. A systematic variation in the structures was carried out to understand the effect of position and chain length on the mesophase behavior. In the case of single alkoxy chain at 4-position, there is a transition from Smectic C to Smectic A mesophase during cooling and Smectic A to Smectic C transition in heating cycle in all the homologues except n = 6 & n = 8. In the case of two alkoxy chains at 3-, 5-positions, the compounds are non-mesogenic in nature. On changing the position of alkoxy chains from 3-, 5-positions to 3-, 4-positions, intermolecular forces weaken and these compounds become liquid crystalline and show columnar rectangular mesophase resulting from the effect of regioisomerism. Moving on to the series with three alkoxy chains, it was observed that 2-, 3-, 4-trialkoxy substituted compounds exhibit columnar rectangular mesophase except lower chain length (n = 6 & 8) while 3-, 4-, 5-trialkoxy substituted aroylhydrazones show columnar rectangular mesophase; except n = 10 which shows columnar oblique mesophase. Thus it was established that on increasing density of alkoxy chains around one terminal, mesophase changes from smectic to columnar mesophase. Temperature dependent Raman studies confirm the presence of intermolecular hydrogen bonding. Further, effect of substitution pattern did not show much influence on the photophysical properties of the mesogenic series in solid and solution state. However, the non-mesogenic series showed a different absorption and emission transition from the mesogenic series in solid and solution state. Solid state fluorescence studies show almost similar emission maxima in all the series. However, it was also noticed that non-mesogenic series show maximum red shifted emission maxima in solid state as compared to that of solution. All the series showed good gelation properties with less than 1% CGC (wt%) suggesting the strong ability of molecules to form gel. These H-bonded liquid-crystalline gels have immense potential for applications in emissive displays.

Triphenylamine-Thienothiophene Organic Charge-Transport Molecular Materials: Effect of Substitution Pattern on their Thermal, Photoelectrochemical, and Photovoltaic Properties.

Two readily accessible thienothiophene-triphenylamine charge-transport materials have been synthesized by simply varying the substitution pattern of the triphenylamine groups on a central thienothiophene π-linker. The impact of the substitution pattern on the thermal, photoelectrochemical, and photovoltaic properties of these materials was evaluated and, based on theoretical and experimental studies, we found that the isomer in which the triphenylamine groups were located at the 2,5-positions of the thienothiophene core (TT-2,5-TPA) had better π-conjugation than the 3,6-isomer (TT-3,6-TPA). Whilst the thermal, morphological, and hydrophobic properties of the two materials were similar, their optoelectrochemical and photovoltaic properties were noticeably impacted. When applied as hole-transport materials in hybrid perovskite solar cells, the 2,5-isomer exhibited a power-conversion efficiency of 13.6 %, much higher than that of its 3,6-counterpart (0.7 %) under the same standard conditions.

Solution-Processable Field-Effect Transistor Behavior of π-Conjugated Oligothiophene

The effect of substitution pattern of the linear-type π-conjugated oligothiophenes is examined. The material solubility, thermal properties, and charge transport characteristics of two hexyl subsituted quinquethiophenes (DH5T) were determined along with the characteristics of an organic field-effect transistor (OFET). The solubility of 4,7-bis (3’-hexyl-2,2’-bithiophene-5-yl) thiophene (β-DH5T), which featured a lateral substitution, was significantly better than that of α,α’-dihexylquinquethiophene (α-DH5T) by altering the directional position of the alkyl group, which makes it a good candidate for solution-processed OFETs. Despite the well-defined vertical alignment of α-DH5T, the hole mobility of the β-DH5T film (3.02 × 10–3 cm2 V–1 s–1) was one order of magnitude higher than the hole mobility of the α-DH5T film (2.47 × 10–4 cm2 V–1 s–1) prepared by solution processing.

Phenothiazine decorated carbazoles: effect of substitution pattern on the optical and electroluminescent characteristics.

A series of thienylphenothiazine decorated carbazoles were synthesized and characterized by optical, electrochemical, thermal, and theoretical investigations. Absorption spectra of the compounds are influenced by the substitution pattern and chromophore number density. Compounds containing 2,7-substitution exhibited red-shifted absorption, while the chromophore loading on the other positions led to the increment in molar extinction coefficients due to the increase in the chromophore density. Multiple substitutions resulted in twisting of chromophores and affected the conjugative delocalization of the π-electrons, which produced shorter wavelength absorption for the 2,3,6,7-tetrasubstituted derivative. Interestingly, the compounds exhibited excited-state solvatochromism attributable to the structural reorganization-induced electronic perturbations. The solvatochromic data are supportive of a general solvent effect, which is further confirmed by Lippert-Mataga correlation. End-capping with butterfly shaped phenothiazine restrained the formation of molecular aggregates in the solid state. All of the compounds displayed exceptional thermal stability attributable to the rigid carbazole building block. Solution processed OLED fabricated using the new materials as emitting dopants in 4,4'-bis(9H-carbazol-9-yl)biphenyl host exhibited bluish green electroluminescence.

Similar and Different: Effect of Substitution Pattern on the Aggregation-Induced Emission Property of [4'-(bisphenylamino)[1,1']biphenyl]methylene Fluorenes

Three isomers, [4'-(bisphenylamino)[1,1']biphen-2-yl]methylenefluorene (BAB2MF), [4'-(bisphenylamino)[1,1']biphen-3-yl]methylenefluorene (BAB3MF) and [4'-(bisphenylamino)[1,1']biphen-4-yl]methylenefluorene (BAB4MF), were synthesized through Suzuki coupling. The substitution pattern exerts a dramatic influence on the optical property. BAB3MF and BAB4MF are hardly emissive either in the solution or as solid state. On the contrary, BAB2MF emits strongly, especially in the aggregate state with a high fluorescent quantum yield of 69%. Furthermore, BAB2MF shows an aggregation-induced enhanced emission behavior. BAB2MF solid emits at 488 nm, about 60 nm blue-shifted from its solution.

Equilibrium and structural characterization of ofloxacin–cyclodextrin complexation

The enantiomer-specific characterization of ofloxacin–cyclodextrin complexes was carried out by a set of complementary analytical techniques. The apparent stability constants of the ofloxacin enantiomers with 20 different cyclodextrins at two different pH values were determined to achieve good resolution capillary electrophoresis enantioseparation either to establish enantioselective drug analysis assay, or to interpret and design improved host–guest interactions at the molecular level. The cyclodextrins studied differed in the nature of substituents, degree of substitution (DS), charge and purity, allowing a systematic test of these properties on the complexation. The seven-membered beta-cyclodextrin and its derivatives were found to be the most suitable hosts. Highest stability and best enantioseparation were observed for the carboxymethylated-beta-cyclodextrin (DS ~ 3.5). The effect of substitution pattern (SP) was investigated by molecular modeling, verifying that SP greatly affects the complex stability. Induced circular dichroism was observed and found especially significant on carboxymethylated-beta-cyclodextrin. The complex stoichiometry and the geometry of the inclusion complexes were determined by 1H NMR spectroscopy, including 2D ROESY techniques. Irrespective of the kind of cyclodextrin, the complexation ratio was found to be 1:1. The alfa-cyclodextrin cavity can accommodate the oxazine ring only, whereas the whole tricyclic moiety can enter the beta- and gamma-cyclodextrin cavities. These equilibrium and structural information offer molecular basis for improved drug formulation.

In vitro and in vivo photocytotoxicity of boron dipyrromethene difluoride for photodynamic therapy

To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the “heavy atom effect” or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G2/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY st...

Enantioselective Hydrolysis of Glycidyl Methylphenyl Ethers by Botryosphaeria Dothidea ZJUZQ007: Effect of Substitution Pattern on Enantioselectivity

Resolution of racemic glycidyl (o, m, p)-methylphenyl ethers by using a newly isolated Botryosphaeria dothidea ZJUZQ007 with epoxide hydrolase activity affords enantiopure epoxides with enantiomeric excesses (e.e.(s)) of 91-99% and enantiomeric ratios (E) of 18.1 to 48.6. The (R)-enantiomer was obtained from rac-glycidyl (o or m)-methylphenyl ethers whereas the (S)-epoxides was obtained from glycidyl p-methylphenyl ether. Substitution pattern of the methyl group exerted effects both on configurations of the remaining epoxides and enantioselectivities of epoxide hydrolase. The observations were explained by enzyme-substrate docking studies. It is the first example showing that for kinetic resolution of glycidyl methylphenyl ethers, fungal species of B. dothidea was applied.

Tetrathiophenes with thiophene side chains: effect of substitution on packing and conjugation

Abstract The effect of substitution pattern on conjugation and packing has been investigated by synthesizing a series of tetrathiophenes with systematically varied alkyl thiophene substituents.

Comparable stabilisation, structural changes and activities can be induced in FGF by a variety of HS and non-GAG analogues: implications for sequence-activity relationships

The activities of heparan sulfate (HS) and heparin do not correlate simply with sulfation levels or sequence. The alternative hypothesis, that appropriate charge and conformational characteristics for protein binding and activity can be provided by other sequences in heparan sulfate and, possibly, also in unrelated sulfated polysaccharides, is explored. Differential scanning fluorimetry was used to measure the thermostabilisation bestowed by modified heparin polysaccharides (proxies for heparan sulfate) on fibroblast growth factor-1 (FGF-1) and fibroblast growth factor-2 (FGF-2), prototypical heparan sulfate-binding proteins, revealing varied abilities and primary sequence-activity redundancy. The effect of substitution pattern on the heparin/heparan sulfate backbone was explored using principal component analysis of (13)C NMR chemical shift data for homogeneously modified heparin polysaccharides revealing complex conformational effects. No simple relationship emerged between these polysaccharides, with their distinct charge distributions and geometries, and their ability to signal. Other, structurally unrelated sulfated polysaccharides were also able to support signalling. These influenced FGF stabilisation in a similar manner to the HS analogues and provided analogous cell signalling activity. For FGF-1, but not FGF-2, signaling correlated strongly with protein stabilisation and circular dichroism spectroscopy demonstrated that some non-HS polysaccharides invoked comparable secondary structural changes to those induced by heparin. Active conformations can readily be found in several heparin derivatives, as well as among non-HS polysaccharides, which comprise unrelated primary sequences, confirming the hypothesis and implying that the level of unique information contained in HS sequences may be much lower than previously thought.

Structural cleavages, electoral competition and partisan divide: A Bayesian multinomial probit analysis of Chile's 2005 election

The transformations in Chile's party structure since 1989 have led several authors to examine the main cleavages shaping partisan divisions and the impact of different factors on citizens' party preferences. Previous studies, however, failed to analyze the effect of these variables on actual vote choice and neglected the influence of election-specific factors. In order to address these issues, we implement a Bayesian multinomial probit model to analyze Chile's 2005 election. We show that, while both socio-demographic variables and attitudes towards democracy affected voter behavior, the latter were the main determinants of the choice between Chile's two main political coalitions. In addition, we find that the presence of a second conservative candidate, together with voters' strategic considerations, significantly affected candidate choice. These results cannot be accounted for by analyses focused on citizens' party identification or by methodologies that ignore the effect of substitution patterns between candidates on voters' electoral behavior.

Blue‐emitting poly(1,3‐phenylenevinylene) derivatives: Effect of substitution patterns on optical properties

AbstractBlue‐emitting poly{[5‐(diphenylamino)‐1,3‐phenylenevinylene]‐alt‐(2‐hexyloxy‐5‐methyl‐1,3‐phenylenevinylene)} (3), poly{[5‐bis‐(4‐butyl‐phenylamino)‐1,3‐phenylenevinylene]‐alt‐(1,3‐phenylene vinylene)} (4), and poly(2‐hexyloxy‐5‐methyl‐1,3‐phenylenevinylene) (5) were synthesized by the Wittig–Horner reaction. Although polymers 3–5 possess fluorescent quantum yields of only 13–34% in tetrahydrofuran solution, their films appear to be highly luminescent. Attachments of substituents tuned the emission color of thin films to the desirable blue region (λmax = 462–477 nm). Double‐layer light‐emitting‐diode devices with 3 and 5 as an emissive layer produced blue emission (λem = 474 and 477 nm) with turn‐on voltages of 8 and 11 V, respectively. The external quantum efficiencies were up to 0.13%. © 2005Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2800–2809, 2005

EPR study of positive holes on phenylene vinylene chains: from dimer to polymer

Isolated radical cations of substituted oligomers and polymers of phenylene vinylenes (PV) produced by irradiation in glassy toluene solutions were characterized by EPR. It was shown that the linewidth of the EPR signal from radical cations in oligomers decreased with increasing the number of repeat PV units, at least, up to n=8. This result implies extensive delocalization of hole on the isolated PV chain. In the case of polymer (MEH-PPV), the EPR signal linewidth is substantially smaller than the extrapolated value for oligomer radical cations, which was tentatively explained by the effect of substitution pattern.

The effect of substitution patterns on the release rates of opioid peptides DADLE and [Leu 5]-enkephalin from coumarin prodrug moieties

A coumarin-based prodrug system has been developed in our laboratory for the preparation of esterase-sensitive prodrugs of amines, peptides, and peptidomimetics. The drug release rates from this prodrug system were found to be dependent on the structural features of the drug moiety. The effect of the phenyl ring substitutions on the release kinetics of such prodrugs of model amines was examined recently and it was found that appropriately positioned alkyl substituents on the phenyl ring could help to facilitate the release. Aimed at further understanding the structure–release rate relationship of the coumarin-based cyclic prodrugs, we synthesized and examined a series of substituted coumarinic acid derivatives of opioid peptides, DADLE, and [Leu 5]-enkephalin.

Controlling the rates of reductively-activated elimination from the (indol-3-yl)methyl position of indolequinones

A series of substituted 3-(4-nitrophenyloxy)methylindole-4,7-diones (Q) were synthesised. The effects of substitution patterns on the indole core on rates of elimination of 4-nitrophenol as a model for drug release following fragmentation of a phenolic ether linker were studied. After reduction to either the radical anion (Q˙−) or hydroquinone (QH2) elimination of 4-nitrophenol occurred from the (indol-3-yl)methyl position. The half-lives of Q˙− radicals at [O2] ≈ 5 µmol dm−3, typical of tumour hypoxia, were t½ ≈ 0.3–1.8 ms, the higher values associated with higher reduction potentials. Half-lives for the autoxidation of the QH2 were markedly longer at the same oxygen concentration (t½ ≈ 8–102 min) and longer still in the presence of 4 µmol dm−3 superoxide dismutase (t½ ≈ 8–19 h). Although the indolequinones were able to eliminate 4-nitrophenol with high efficiency only Q˙− radicals of the 3-carbinyl substituted derivatives did so with sufficiently short half-lives (t½ ≈ 41–2 ms) to compete with electron transfer to oxygen and therefore have the potential to target the leaving group to hypoxic tissue. The hydroquinones are not sufficiently oxygen sensitive to prevent the elimination of 4-nitrophenol (t½ ≈ 1.5–3.5 s) even at oxygen concentrations expected in normal tissue. By incorporating electron rich substituents at the indolyl carbinyl position it is possible to control the rate of reductive fragmentation. This may prove an important factor in the design of an indolequinone-based bioreductive drug delivery system.