Hydroxyphenyl Substituents Research Articles

Electrocatalytic Hydrogen Evolution of the Cobalt Triaryl Corroles Bearing Hydroxyl Groups

AbstractThree isomeric A2B‐type new cobalt triaryl corroles bearing hydroxyphenyl substituents have been prepared and well characterized. Their activity and stability in the electrocatalytic hydrogen evolution reaction (HER) have been investigated. The results showed that the hydroxyl position of the phenyl group had significant influence on electrocatalytic HER. The ortho‐hydroxyphenyl substituted cobalt corrole (1) core displays the best HER activity using TsOH proton source, and the turnover frequency (TOF) and catalytic efficiency (C.E) reach 318.68 s−1 and 1.13, respectively. Moreover, a turnover number (TON) of 1447.39 and Faraday efficiency (FE) of 98.7 % have been observed in aqueous medium. The catalytic pathway is via EECEC, EECC or ECEC pathways depending on the acidity of acid proton source (E: electron transfer step, C: chemical step, in this case protonation). The catalytic HER performance of these cobalt corroles follows an order of o‐hydroxyl > p‐hydroxyl > m‐hydroxyl isomer, showing the o‐ and p‐hydroxyl of the phenyl groups are more efficient in accelerating proton relay.

Regioselective Synthesis of 2-Aryl-5-cyano-1-(2-hydroxyaryl)-1H-imidazole-4-carboxamides Self-Assisted by a 2-Hydroxyaryl Group.

The reactivity of the diaminomaleonitrile-based imines containing hydroxyphenyl substituents with diverse aromatic aldehydes has been explored for the synthesis of novel highly substituted nitrogen heterocycles, which are considered privileged scaffolds in drug discovery. We report here a simple and efficient method for the regiocontrolled synthesis of a variety of 2-aryl-5-cyano-1-(2-hydroxyaryl)-1H-imidazole-4-carboxamides from 2-hydroxybenzylidene imines and aromatic aldehydes. Computational studies on the reaction path revealed that the regioselectivity of the reaction toward the formation of imidazole derivatives instead of 1,2-dihydropyrazines, most likely via a diaza-Cope rearrangement, is driven by the 2-hydroxyaryl group in the scaffold. The latter group promotes the intramolecular abstraction and protonation process in the cycloadduct intermediate, triggering the evolution of the reaction toward the formation of imidazole derivatives.

Roaming-like Mechanism for Dehydration of Diol Radicals.

Diol radicals (DRs) are important intermediates in biocatalysis, atmospheric chemistry, and biomass combustion. They are particularly generated from photolysis of halogenated diols and addition of hydroxyl radical to a double bond of unsaturated alcohols, such as lignols. The energized DRs further isomerize/decompose to form products, including water. Aqueous-phase dehydration in radiolytic and biomimetic systems typically occurs at low temperatures, with or without catalysis, whereas the gas-phase dehydration is usually considered energetically unfavorable. In the present study, we propose a new low-energy, roaming-like mechanism based on a detailed dispersion-corrected DFT and ab initio level analysis of the gas-phase dehydration of DRs obtained from the combination of OH radicals with allyl alcohol (AA, CH2═CHCH2OH)-the simplest relevant model of the unsaturated alcohols. The roaming pathways involve a nearly dissociated OH-group, which subsequently abstracts an H atom of the remaining fragment to form water and [C3H5O] radical via a transition state (TS) with energy close to the C-O bond fission asymptote. Two types of roaming-like first-order saddle points (SP) are identified for unimolecular dehydration of 1,2- and 1,3-DR radical adducts involving either both hydroxyl groups of diol radicals to generate an oxygen-centered radical, or β-OH group and a skeletal α-hydrogen atom of the 1,2-DR to form a resonantly stabilized hydroxyallyl radical. Two higher energy conventional (tight) transition states, along with the pathways to 1,2-OH-migration, as well as direct H-abstraction, are also identified and analyzed. Most of the traditional density functional theory methods that have been successfully employed in the literature to locate so-far-known roaming SPs were also able to identify the new mechanism, in accord with dispersion-corrected double hybrid B2PLYP-D3(BJ) and mPW2PLYPD methods involving MP2-correlation corrections. However, the MP2 method itself failed to locate any of them, which seems to be typical for MP2 method for loose TS structures, confirmed here for a flat region of PES connecting direct and roaming saddle points. However, MP2 method correctly locates an identical roaming SP for a larger p-coumaryl alcohol model involving hydroxyphenyl substituent at Cγ atom of AA. Two types of interfragmental interactions are identified that stabilize the roaming SPs: (a) H-bonding of the leaving OH radical either with the H atom of the remaining OH group, or with π-cloud of the double bond; (b) direct interaction of π-electrons with the lone-pair electrons of the heteroatom in the leaving OH group through the TS-ring. The alternative TSs are qualitatively characterized by "collinearity" angle of the OH radical attack on the O-H/C-H bonds of the substrate in abstraction-like O-H-O geometry, attributed to the improved orbital overlaps. The proposed mechanism presents broader implications to signify, particularly, a larger role in atmospheric and combustion processes, especially biomass pyrolysis.

Photogeneration of Singlet Oxygen by Tetra(p-Hydroxyphenyl)porphyrins Modified with Oligo- and Polyalkylene Oxides

Mono- and diethylene oxide derivatives of tetra(p-hydroxyphenyl)porphyrin (THPP) with different conformation states are synthesized. These compounds exhibit high photosensitization activity in the generation of singlet oxygen in organic and aqueous (in the solubilized state) phases. It is shown that introducing ethylene oxide moieties into the hydroxyphenyl substituents of THPP increases its solubility in chloroform. In addition, the activity of singlet oxygen 1Δg generation in the reaction of anthracene photooxidation by THPP tetra derivatives in chloroform, where the ethylene oxide fragments are introduced into two phenyl rings and hexadecyl fragments are introduced into another two, is higher than the activity of mono- and di-modified THPP molecules with enthylene oxide molecules at one hydroxyphenyl cycle. The activity of tetra-substituted porphyrin in chloroform, however, is comparable to that of nonsubstituted tetraphenylporphyrin, considered to be one of the most active photosensitizers. The produced ethylene oxide derivatives of THPP are solubilized with pluronic F-127 (triblock copolymer of ethylene- and propylene-oxides)—one of the least toxic and effective polymeric detergents—forming water-soluble forms of the respective porphyrins. It is established that the pluronic solubilization capability (the lowest molar concentration of pluronic required for the complete transfer of porphyrin of a particular molar concentration dissolved in organic phase to the water-soluble form) is higher for asymmetrical mono- and di-derivatives of the THPP than for symmetric tetra-substituted THPP. It is shown that the activity of the solubilized water-soluble form of mono- and tetra-derivatives in tryptophan photoxidation is higher than that of unsubstituted THPP and is comparable to the activity of tetraphenylporphyrin.

Fluorescence of Hydroxyphenyl-Substituted "Click" Triazoles.

The structural and optical properties of hydroxyphenyl-substituted-1,2,3-triazole molecules ("click" triazoles) are described. "Click" triazoles are prepared from the copper(I)-catalyzed azide-alkyne cycloaddition reactions. The alkyne-derived C4 substituent of a "click" triazole engages in electronic conjugation more effectively with the triazolyl core than the azide-derived N1 substituent. Furthermore, triazolyl group exerts a stronger electron-withdrawing effect on the N1 than the C4 substituent. Therefore, the placement of an electron-donating group at either C4 or N1 position and the presence or the absence of an intramolecular hydrogen bond (HB) have profound influences on the optical properties of these compounds. The reported "click" triazoles have fluorescence quantum yields in the range of 0.1-0.3 and large apparent Stokes shifts (8000-13 000 cm-1) in all tested solvents. Deprotonation of "click" triazoles with a C4 hydroxyphenyl group increases their Stokes shifts; while the opposite (or quenching) occurs to the triazoles with an N1 hydroxyphenyl substituent. For the triazoles that contain intramolecular HBs, neither experimental nor computational results support a model of excited state intramolecular proton transfer (ESIPT). Rather, the excited state internal (or intramolecular) charge transfer (ICT) mechanism is more suitable to explain the fluorescence properties of the hydroxyphenyl-substituted "click" triazoles; specifically, the large Stokes shifts of these compounds.

Synthesis of new alkylsulfonyl(Sulfinyl)-1,2,4-triazole derivatives based on (3-(Alkylthio)-4-R-1,2,4-thriazole-5-yl)(phenyl)methanol’s

In recent years, much attention has been paid to the search and creation of new drugs. Purposeful synthesis of compounds with low toxicity and pronounced biological properties is the main stage in the development of medicinal products. Of particular interest in this direction are nitrogen-containing heterocycles, as highly effective pharmacologically active compounds. Great importance in this direction is given to the study of the biological activity of 1,2,4-triazoles, since the 1,2,4-triazole nucleus is a structural fragment of drugs with variety pharmacological effects. The purpose of our work was to synthesize new compounds in the series of 1,2,4-triazole-3-thione containing hydroxyphenyl substituents, namely synthesise starting compounds, carry out the reactions of alkylation, and study directly oxidation of the Sulfur atom to IV and VI valence states. Materials and methods. The structure of the synthesized compounds, their identity and purity has been proved by elemental analysis, IR-, UV-spectrophotometry, NMR-spectrometry, TLC, HPLC-MS. Results. We obtained a number of 1,2,4-triazole-3-thione derivatives, namely, oxidized forms of s-alkyl derivatives, which have practical significance for drug developers, as well as for scientists in the field of organic synthesis. For the obtained compounds it is planned to study acute toxicity, antifungal, antimicrobial, neuroleptic, diuretic, anti-inflammatory, antioxidant, hypolipidemic activity. But the pharmacological activity of 1,2,4-triazole-3-thione has not been studied sufficiently. From our point of view, the synthesis, study of physical-chemical and biological properties of 1,2,4-triazole-3-thione with hydroxyphenyl substituents have a scientific novelty, theoretical and practical significance. Therefore, the further search for biologically active substances in this series of compounds continues. Conclusions. The thirteen new biological active compounds (3-(alkylsulfonyl(sulfinyl))-4-R-1,2,4-triazole-5-il)(phenyl)methanols have been synthesized. Their structure has been confirmed using modern methods of analysis.

Spectroscopic characterization of free-base hydroxy(arylethynyl)porphyrins in acidic and basic media

The addition of arylethynyl groups to the porphyrin macrocycle represents an effective strategy with which to enhance the light-harvesting properties of porphyrins. We now extend this modification to arylethynyl porphyrins with two or four [Formula: see text]-hydroxyphenyl substituents. Arylethynyl porphyrins bearing four, but not two, [Formula: see text]-hydroxyphenyl substituents show evidence of aggregation under acidic conditions. Under basic conditions, deprotonation of the peripheral hydroxyphenyl substituents results in substantially red-shifted spectral features and enhanced absorption in the Q-band region. When the hydroxyphenyl groups are appended to the porphyrin macrocylce via the ethynyl spacers, the spectral shifts observed upon deprotonation are significantly enhanced relative to those observed for hydroxyphenylporphyrins, highlighting the role of expanded conjugation in altering porphyrin photophysics.

Synthesis of new triazole based imidazo[1,2-a]pyrazine-benzimidazole conjugates: H-bonding assisted FRET efficient ratiometric detection of pyrophosphate

Abstract Triazole tethered imidazo[1,2- a ]pyrazine-benzimidazole conjugates 13-38 has been synthesized by click and Suzuki-Miyaura cross coupling reactions at C-8 and C-6 positions, respectively. The research findings clearly predicted that by modification of electronic structure of the receptor, the sensitivity of the recognition process could be modified. Compound 24 with hydroxyphenyl substituent, showed stronger binding to the pyrophosphate than other compounds. Compound 24 has been used as selective probe for ratiometric detection of pyrophosphate amongst the other anions. The binding event of compound 24 toward PPi has been successfully evaluated by absorption and emission spectroscopy as well as NMR titration method. The compound 24 showed H-bonding assisted facilitation of FRET phenomenon in the presence of PPi.

Synthesis and theoretical investigation of some new 4-substituted flavylium salts.

Flavylium salts substituted at 4-position with hydroxyphenyl substituents were synthesized by acidic condensation according to a slightly modified procedure described by Robinson and Walker. Their thermodynamic properties and conformational analysis have been studied at DFT level.

Synthesis, chemosensing properties and logic behaviour of a novel ratiometric 1,8-naphthalimide probe based on ICT and PET

A novel fluorescence sensing 1,8-naphthalimide designed on the “receptor1-fluorophore-spacer-receptor2” model is synthesized and investigated. The novel probe comprising aminotriazole and hydroxyphenyl substituents is capable to operate simultaneously via ratiometric ICT and PET signalling mechanism. The synthesized compound shows excellent signalling properties towards protons, hydroxyl anions and Cu2+ ions. Due to the remarkable fluorescence changes in the presence of these analytes the system is able to act as a two output combinatorial logic circuit with three chemical inputs. Input3-Disabled XNOR, INHIBIT and IMPLICATION logic gates were obtained. Because of the parallel action of disabled-XNOR and disabled-INHIBIT gates a magnitude digital comparator with disable capability is achievable.

Optical properties of porphyrin–Eu-β-diketonate supramolecular nanostructures

Hybrid nanostructures obtained by the assembly of organic/inorganic chemical systems can show novel molecular properties. The combination of different optical properties belonging to different molecular components represents an advanced method to manufacture hybrid assemblies useful for improved optical applications. In our study, silanized quartz substrates were functionalized with a covalent tetrakis hydroxyphenyl porphine monolayer. The remaining hydroxyphenyl substituents, not involved in the covalent bond with the silane coupling layer, allowed additional functionalization with the tris(dibenzoylmethane) mono(5-amino-1,10-phenanthroline)europium(III) complex by means of ionic interactions. X-ray photoelectron spectroscopy and UV-visible spectrophotometry gave indication of the porphyrin–Eu-complex grafting mode. In these supramolecular architectures both through bond (covalent) and through space (mainly ionic) electronic interactions between the two molecular units resulted in unprecedented macroscopic properties. In fact, emission measurements confirmed that the porphyrin and Eu-complexes influence each other and the photoluminescence relative intensities are strongly affected.

Aggregation Properties of Hyperporphyrins with Hydroxyphenyl Substituents

Acidification of tetrakis(4-hydroxyphenyl)porphyrin (THPP) and tetrakis(3,5-dihydroxyphenyl)porphyrin (OHPP) in dichloromethane solutions has been investigated as a function of the nature of the counteranion. These porphyrins exhibit different patterns of behavior, and extended aggregates are formed displaying broad extinction features together with intense components due to resonant light scattering. Especially in the case of haloacids, J-aggregated species are obtained exhibiting large bathochromic shifts both for B- and Q-bands, which extend in the far red region. The optical characteristics of the aggregated and monomeric protonated species are strongly influenced by the nature of the counteranions. A comparison with tetrakis(4-methoxyphenyl)porphyrin (TMPP), which remains always in a monomeric form, demonstrates the key role played by the peripheral hydroxyl groups in stabilizing various porphyrin aggregates.

Synthesis and versatile supramolecular self-assembly of the 5,15-bis(4-hydroxyphenyl)-10,20-bis(4-carboxyphenyl)porphyrin scaffold

This study reports the synthesis of the 5,15-bis(4-hydroxyphenyl)-10,20-bis(4-carboxyphenyl)porphyrin (BBP) moiety, and its versatile self-assembly into multiporphyrin hydrogen-bonding ‘polymers’ in four different reaction and crystallization conditions. In two cases the polymers are sustained by characteristic intermolecular cyclic dimeric (COOH)2 hydrogen-bond synthons between the carboxyphenyl functions of neighboring species, which face one another along a common equatorial axis of the porphyrin building blocks. The hydroxyphenyl substituents, which are directed perpendicular to the porphyrin chains, form either O–H⋯O(dioxane) or O–H⋯N(pyridine) weak hydrogen bonds by donating their protons to the solvent guest species. In the third example, the multiporphyrin chains are tessellated by rather unusual pairs of OH⋯OC(OH) hydroxyl–carboxyl hydrogen bonds between cis-related arms of adjacent porphyrin species along opposite directions of the polymer. Here the carboxylic protons are donated to the carbonyl site of the ethyl benzoate guest, thus linking the latter to the side surfaces of the polymeric chain. The fourth structure, which involves chain polymers of deprotonated porphyrin building blocks, is sustained by strong symmetric [–COO⋯H⋯OOC–]− hydrogen bonds along the chains. These chains aggregate further into complex three-dimensional architecture by weaker hydrogen bonds through bridging water molecules. The observed diversity of the intermolecular binding patters suggests that the BBP scaffold is not well suited for a programmed construction of network solids.

New Bis(chalcones) and Their Transformation into Bis(pyrazoline) and Bis(pyrazole) Derivatives

AbstractThe reaction of bis(chalcones) 1a−d and bis(chalcone) tetrabromo derivatives 3a−d with hydrazine hydrate gave bis(pyrazolines) 4a−d and bis(pyrazoles) 5a−d, respectively. Bis(pyrazoles) 5e,f bearing hydroxyphenyl substituents have been prepared from the reaction of bis(chromones) 6c,d with hydrazine hydrate, because their synthesis from the corresponding benzyloxy‐substituted 5c,d gave very poor yields. The structures of all new compounds have been established by extensive NMR spectroscopic studies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Drug features that contribute to the activity of quinolones against mammalian topoisomerase II and cultured cells: correlation between enhancement of enzyme-mediated DNA cleavage in vitro and cytotoxic potential

CP-115,953 [6,8-difluoro-7-(4'-hydroxyphenyl)-1-cyclopropyl-4- quinolone-3-carboxylic acid] is a novel quinolone that is highly active against topoisomerase II in vitro and in mammalian cells in culture (M. J. Robinson, B. A. Martin, T. D. Gootz, P. R. McGuirk, M. Moynihan, J. A. Sutcliffe, and N. Osheroff, J. Biol. Chem. 266:14585-14592, 1991). However, the features of the drug that contribute to its activity towards mammalian systems have not been characterized. Therefore, CP-115,953 and a series of related quinolones were examined for their activity against calf thymus topoisomerase II and cultured mammalian cells. CP-115,953 stimulated DNA cleavage mediated by the type II enzyme with a potency that was approximately 600-fold greater than that of the antimicrobial quinolone ciprofloxacin and approximately 50-fold greater than that of the antineoplastic drug etoposide. As determined by the ability to enhance enzyme-mediated DNA cleavage, quinolone activity towards calf thymus topoisomerase II was enhanced by the presence of a cyclopropyl group at the N-1 ring position and by the presence of a fluorine at C-8. Furthermore, the 4'-hydroxyphenyl substituent at the C-7 position was critical for the potency of CP-115,953 towards the mammalian type II enzyme. In this regard, the aromatic nature of the C-7 ring as well as the presence and the position of the 4'-hydroxyl group contributed greatly to drug activity. Finally, the cytotoxicity of quinolones in the CP-115,953 series towards mammalian cells paralleled the in vitro stimulation of DNA cleavage by topoisomerase II rather than the inhibition of enzyme-catalyzed DNA relaxation. This correlation strongly suggests that these quinolones promote cell death by converting topoisomerase II to a cellular poison.

Synthesis of 2- and 4-chloropyrimidines with hydroxyphenyl substituents by the interaction of Vilsmeier-Haack reagents with (hydroxyphenyl)dihydropyrimidin-2- and -4-ones

The reaction of 2- and 4-hydroxypyrimidines containingortho- andpara-hydroxyphenyl substituents with Vilsmeier-Haack reagents generatedin situ from DMF and SOCl2 or POCl3 results in the chemoselective replacement of the heterocyclic hydroxyl group by chlorine and formylation of the phenolic hydroxyl group. Aryl formates are hydrolyzed under the conditions of their isolation to give the corresponding phenols, especially if the pyrimidyl fragment isortho to the formyloxy group.

Analogs of cannabinoids: synthesis of some 7H-indolo-, 5H-imidazolo, 7H-benzimidazolo[1,2-c] [1,3]benzoxazines – novel ring systems

Tetrahydrocannabinol 1, the active constituent of CannabissativaLinn, is a well-known CNS-active compound and introduction of a nitrogen atom at the ring junction of the pyran and alicyclic ring is of considerable interest. This prompted the synthesis of 7H-indolo[1,2-c] [1,3]-, 5H-imidazolo[1,2-C] [1,3],- and 7H-benzimidazolo[1,2-c] [1,3]-benzoxazine, a novel heterocyclic system. 2-(2′-Hydroxyphenyl) indoles, 2-(2′-hydroxyphenyl) imidazoles, and 2-(2′-hydroxyphenyl) benzimidazoles are suitable intermediates for the preparation of this type of benzoxazines, as the second heterocycle (ring B) can then be constructed by introduction of a methylene bridge between the hydroxyl of the 2′-hydroxy phenyl substituent and the imino group of the heterocyclic system.