Substituents In Para Position Research Articles

Synthesis and Enzymatic Evaluation of a Small Library of Substituted Phenylsulfonamido-Alkyl Sulfamates towards Carbonic Anhydrase II.

A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, 1b-79b, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates 1a-79a, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds 1a-79a showed no inhibition of the enzyme, in contrast to sulfamates 1b-79b. Thus, the inhibitory potential of compounds 1b-79b towards this enzyme depends on the substituent and the substitution pattern of the phenyl group as well as the length of the spacer. Bulkier substituents in the para position proved to be better for inhibiting CAII than compounds with the same substituent in the meta or ortho position. For many substitution patterns, compounds with shorter spacer lengths were superior to those with long chain spacers. Compounds with shorter spacer lengths performed better than those with longer chain spacers for a variety of substitution patterns. The most active compound held inhibition constant as low as Ki = 0.67 μM (for 49b) and a tert-butyl substituent in para position and acted as a competitive inhibitor of the enzyme.

Synthesis of New Chroman-4-one Based 1,2,3-Triazole Analogues as Antioxidant and Anti-Inflammatory Agents.

A library of new chroman-4-one based 1,2,3-triazole analogues were synthesized involving a series of condensation, cyclization, Suzuki coupling and copper catalysed click chemistry protocols. The newly synthesized compounds 8a-l were screened for their invitro antioxidant and anti-inflammatory activities by employing Ascorbic acid and Diclofenac as reference drugs respectively. The compound without any substituent on benzyl ring (8a), compound with -Cl substituent in para position of benzyl ring (8i), and compound with ethoxy substituent in para position of benzyl ring (8k) exhibited potent antioxidant and anti-inflammatory activities with higher percentage of inhibition. To understand their binding affinities, molecular docking study of these three compounds performed against NADPH oxidase with presented outstanding docking scores and promising binding interactions like H-bond and hydrophobic.

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells.

Evaporable indano[60]fullerene ketone (FIDO) was converted to indano[60]fullerene thioketone (FIDS) in high yield by using Lawesson's reagent. Three compounds with different substituents in para position were successfully converted to the corresponding thioketones, showing that the reaction tolerates compounds with electron-donating and electron-withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives (FIDO, FIDS, C60) as electron-acceptors were compared, and the open-circuit voltage with FIDS was 0.16 V higher than that with C60.

Network topology diversification of porous organic salts.

Hydrogen-bonded organic frameworks (HOFs) are porous organic materials constructed via hydrogen bonds. HOFs have solubility in specific high-polar organic solvents. Therefore, HOFs can be returned to their components and can be reconstructed, which indicates their high recyclability. Network topologies, which are the frameworks of porous structures, control the pore sizes and shapes of HOFs. Therefore, they strongly affect the functions of porous materials. However, hydrogen bonds are usually weak interactions, and the design of the intended network topology in HOFs from their components has been challenging. Porous organic salts (POSs) are an important class of HOFs, are hierarchically constructed via strong charge-assisted hydrogen bonds between sulfonic acids and amines, and therefore are expected to have high designability of the porous structure. However, the network topology of POSs has been limited to only dia-topology. Here, we combined tetrasulfonic acid with the adamantane core (4,4',4'',4'''-(adamantane-1,3,5,7-tetrayl)tetrabenzenesulfonic acid; AdPS) and triphenylmethylamines with modified substituents in para-positions of benzene rings (TPMA-X, X = F, methyl (Me), Cl, Br, I). We changed the steric hindrance between the adamantane and substituents (X) in TPMA-X and obtained not only the common dia-topology for POSs but also rare sod-topology, and lon- and uni-topologies that are formed for the first time in HOFs. Changing template molecules under preparation helped in successfully isolating the porous structures of AdPS/TPMA-Me with dia-, lon-, and sod-topologies which exhibited different gas adsorption properties. Therefore, for the first time, we demonstrated that the steric design of HOF components facilitated the formation, diversification, and control of the network topologies and functions of HOFs.

New fluorescent derivatives from papaverine: Two mechanisms to increase the quantum yield

A series of new emissive imidazo[5,1-a]isoquinolines were synthesized, and their electronic properties investigated, compared, and discussed in light of their chemical structure. The electronic spectra show absorption bands around 330–350 nm and intense fluorescence emissions between 440 nm and 460 nm, with corresponding huge Stokes shifts (6464-8611 cm−1). Depending on the position and the electronic properties of the substituents on the imidazo[5,1-a]isoquinoline nucleus, the emission quantum yield in dichloromethane solution enhances from 9% to 37%. The collected data suggest that two distinct mechanisms are responsible for the enhanced emission: the steric hindering of the rotation of the substituent and its electronic effect, improved by the molecular planarization attainable exclusively with electron-withdrawing substituents in para position.

The substituent effect on CW laser beam self-action manifestation under UV irradiation of azo-azomethine PMMA composites thin films

We report synthesis and study of E→Z→E photoswitching transformations of methyl-substituted azo-aldehyde and six novel corresponding azo-azomethines containing electron withdrawing/donating substituents in para-position to – CHN– bond, being analyzed by UV–Vis and 1H NMR spectroscopy techniques. Impact of donor/acceptor substituent nature on isomerization kinetics was studied in THF solutions by light activation at 390 nm. We obtained high optical quality of PMMA thin films doped with mentioned dyes. It was characterized with both angularly resolved optical elastic scattering data and nonlinear refractive/absorptive optical responses analysis via CW laser beam self-action effects manifestation at wavelength 532 nm. Pronounced self-focusing effect contribution was shown for electron donating substituents (-CH3, -OCH3) and self-defocusing one for electron withdrawing -NO2 group. UV irradiation at 254 nm provides switching from self-defocusing to self-focusing mode of -NO2 substituted dye-doped film with refractive nonlinear optical response efficiency Re(χ(3)) ≈10−2 esu on background of moderate photoinduced absorption effects manifestation.

Photophysical and optical properties of 4-(4'-(diphenylamino)benzylidene)-2-phenyloxazol-5(4H)-ones induced by the peripheral substituent

Photophysical and optical properties of 4-(4'-(diphenylamino)benzylidene)-2-phenyloxazol-5(4H)-ones differing in the peripheral substituent have been investigated in chloroform, solvent mixture, polymer matrix and solid state. These properties are influenced by the nature of the substituent on the phenyl ring and the environment. The dye bearing phenyl group or without substituent in para position of the phenyl group in 2-phenyloxazol-5(4H)-one moiety has the brightest emission in a solid state, whereas the dye with cyano functional group possesses the strongest emission in chloroform. The spectral behavior of the tested dyes is dependent on the solvent mixture. The fluorescence of the oxazolone dye in CHCl3/MeOH was reduced due to hydrogen bond formation, whereas addition of water to the THF or DMSO indicate the enhancement in emission caused by aggregation induced emission (AIE). The absorption and fluorescence spectra of the oxazolone polymer thin film are shifted to blue compared to the dyes dissolved in chloroform.The surface topography of the oxazolone thin films was examined using atomic force microscopy (AFM). The optical properties of the dye layers and dyes immobilized in PMMA matrix were determined by spectroscopic ellipsometry (SE). The absorption coefficient, refractive index, extinction coefficient and the energy bandgap can be effectively manipulated by changing substituent in the dye structure.

Synthesis, biological assessment, and computational investigations of nifedipine and monastrol analogues as anti-leishmanial major and anti-microbial agents.

Leishmaniasis includes a range of parasitic diseases caused by numerous types of the protozoan kinetoplastid parasite. Fungal and bacterial pathogens have led to infectious illnesses causing some main public health problem in current years. A series of dihydropyridine and tetrahydropyrimidine derivatives having fluoro, bromo, and nitro substituents at para-phenyl ring on C4 of dihydropyridine and tetrahydropyrimidine rings were synthesized. Then, anti-leishmanial and antimicrobial potencies of compounds were assessed. All compounds were synthesized via Hantzsch and Biginelli reactions. All derivatives were evaluated for their anti-leishmanial and antimicrobial activities. Moreover, docking and molecular dynamics simulation calculations of the compounds in PRT1 binding site were performed to report the results of anti-leishmanial and antimicrobial activities. Compounds 4a and 4b showed the highest anti-amastigote and anti-promastigote activities. Compound 4a revealed the highest antimicrobial activity against E. coli, P. aeruginosa, and C. albicans strains. In addition, compound 4c showed the highest activity against S. aureus. The fluoro, bromo, and nitro substituents in para-position of phenyl group at C4 of dihydropyridine and tetrahydropyrimidine moieties as well as the bulk and length of the chain linking to the ester moieties are essential for anti-leishmanial and anti-microbial activities of these derivatives. Low cytotoxicity was shown by most of derivatives against macrophages. The molecular docking studies were in agreement with in vitro assay. Moreover, hydrogen binds, RMSF, RMSD, and Rg, strongly showed the steady binding of 4a and 4b compounds in PRT1 active site.

Synthesis and fine-tuning of thermal stability of the negative nitrile-rich photochromes of hydroxytricyanopyrrole (HTCP) series

A series of negative T-type nitrile-rich photochromes containing a hydroxytricyanopyrrole acceptor was synthesized. It was shown that thermal stability of the photoinduced form could be tuned by the replacement of a substituent in para-position to OH-group as well as by the change of a solvent. Ethanol solutions of the synthesized compounds showed significantly shorter half-lives of the reverse dark (thermal) reaction in comparison with solutions in acetonitrile.

The Effect of Methyl and Chloro Substituent Compounds in Amida Derivatives Synthesis from p-Metoxicynamic Acid with Microwaves Irradiation

Background: The difference in the nature of these aromatic amine substituents, i.e. methyl and chloro will affect the N atom of aniline as a nucleophile to attack the carbonyl C atom in the p -methoxcycinnamoyl chloride in the synthesis two amides derivate of p -methoxycinnamic acid, namely N -( p -methylphenyl)- p -methoxycinnamide and N- ( p -chlorophenyl)- p -methoxycinnamide. Aim: to obtain the N -( p -methylphenyl)- p -methoxycinnamide and the N- ( p -chlorophenyl)- p -metoxicinamide compound from p -methoxycinamic acid using the microwave irradiation method as source of energy. Beside that, it also to determine the effect of the presence of methyl and chloro substituents in para position of aromatic amines in the yields of reactions. Method: The reactions were carried out by microwave irradiation at three powers, i.e 120 watts, 200 watts, 280 watts. After separation and purification steps, the products were identified by spectrometric methods. Result: At power of 200 watts for reaction time of 7.5 minutes, the yield of N -( p -methylphenyl)- p -methoxycinamide is larger than N -( p -chlorophenyl)- p -methoxycinnamamide. The percentage of the product synthesis of N -( p -methylphenyl)- p -methoxycinamide was 51.84% and the percentage of N -( p -chlorophenyl)- p -methoxycinnamamide was to 47.20%. Conclusion: The effect of substituent methyl is increase the percentage yield of N -( p -methylphenyl)- p -methoxycinamide compound than that substituent chloro of N -( p -chlorophenyl)- p -methoxycinamide compound under the same reaction conditions. Based on the identification of the structure of the synthesized compound using a UV spectrophotometer, infrared spectrophotomers and 1 H-NMR spectrometer it can be concluded that the synthesized compounds are N -( p -methylphenyl)- p -methoxycinnamide and N - ( p -chlorophenyl)- p -methoxycinnamide.

Synthesis and antimycobacterial activity of disubstituted benzyltriazoles

The increasing prevalence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb), the pathogen of human tuberculosis (TB), serves as a strong incentive for the discovery and development of new agents for the treatment of this plight. In search for such drugs, we investigated a series of benzyltriazole derivatives. We herein report the design, synthesis and biological activity of disubstituted benzyltriazoles against the human virulent H37Rv strain of Mtb as well as the toxicity on human embryonic kidney (HEK-293) cells. The derivative 21 featuring trifluoromethyl substituent in para position on the phenyl ring and n-butyl chain in position 4 on the triazole ring was the most active with MIC90 and MIC99 values of 1.73 and 3.2 µM, respectively, in the albumin-free medium. It also displays high selectivity towards bacteria growth inhibition (SI > 58), thus stands as a better hit for further investigation, including lead optimization, DMPK parameters determination and assessment of its activity in animal models.

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks.

ortho-Fluoroazobenzenes are a remarkable example of bistable photoswitches, addressable by visible light. Symmetrical, highly fluorinated azobenzenes bearing an iodine substituent in para-position were shown to be suitable supramolecular building blocks both in solution and in the solid state in combination with neutral halogen bonding acceptors, such as lutidines. Therefore, we investigate the photochemistry of a series of azobenzene photoswitches. Upon introduction of iodoethynyl groups, the halogen bonding donor properties are significantly strengthened in solution. However, the bathochromic shift of the π→π* band leads to a partial overlap with the n→π* band, making it slightly more difficult to address. The introduction of iodine substituents is furthermore accompanied with a diminishing thermal half-life. A series of three azobenzenes with different halogen bonding donor properties are discussed in relation to their changing photophysical properties, rationalized by DFT calculations.

Synthesis and thermal properties of arylazo pyridone dyes

Thermal degradation properties of 5-(4-substitutedphenylazo)-3-amido-6-hydroxy-4-methyl-2-pyridones and 5-(4-substitutedphenylazo)-3-cyano-6-hydroxy-4-methyl-2-pyridones dyes, differing in electron withdrawing and electron donating substituents in para-position of diazo components were examined. The structure of the synthesized compounds has been confirmed by 1H NMR,13C NMR, FTIR, UV–Vis and XRD analysis techniques. The results obtained with thermogravimetric analysis (TGA) – derivative thermogravimetry (DTG) and differential thermal analysis (DTA) were combined with GC-mass spectral fragmentation to obtain thermal decomposition mechanism. Non-isothermal kinetics were monitored by application of TGA-DTG-DTA. For Kinetic behavior of the investigated dyes during their degradation in an inert atmosphere, Kissinger, Ozawa, Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) isoconversional (model-free) methods were applied. It was found that different thermal stabilities of investigated dyes are the consequence of their different chemical structures, including diverse substituents.

Supramolecular Organogels Based on N-Benzyl, N'-Acylbispidinols.

The acylation of unsymmetrical N-benzylbispidinols in aromatic solvents without an external base led to the formation of supramolecular gels, which possess different thicknesses and degrees of stability depending on the substituents in para-positions of the benzylic group as well as on the nature of the acylating agent and of the solvent used. Structural features of the native gels as well as of their dried forms were studied by complementary techniques including Fourier-transform infrared (FTIR) and attenuated total reflection (ATR) spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and small-angle X-ray scattering and diffraction (SAXS). Structures of the key crystalline compounds were established by X-ray diffraction. An analysis of the obtained data allowed speculation on the crucial structural and condition factors that governed the gel formation. The most important factors were as follows: (i) absence of base, either external or internal; (ii) presence of HCl; (iii) presence of carbonyl and hydroxyl groups to allow hydrogen bonding; and (iv) presence of two (hetero)aromatic rings at both sides of the molecule. The hydrogen bonding involving amide carbonyl, hydroxyl at position 9, and, very probably, ammonium N-H+ and Cl− anion appears to be responsible for the formation of infinite molecular chains required for the first step of gel formation. Subsequent lateral cooperation of molecular chains into fibers occurred, presumably, due to the aromatic π−π-stacking interactions. Supercritical carbon dioxide drying of the organogels gave rise to aerogels with morphologies different from that of air-dried samples.

Reactions of 1‐Arylbenziodoxolones with Azide Anion: Experimental and Computational Study of Substituent Effects

New substituted 1‐arylbenziodoxolones were prepared and their reactivity with azide anion as a nucleophile was investigated. It was found that independent of the presence of substituents, all reactions of 1‐arylbenziodoxolones proceed as nucleophilic substitution of the iodonium leaving group in the electron‐deficient benziodoxolone benzene ring. The presence of bulky substituents in the ortho position of the aryl ring slows the reaction down, while the presence of a moderately electron‐withdrawing bromine substituent in para position to the iodine atom in the benziodoxolone ring moderately increases the rate of substitution. The presence of a strongly electron‐withdrawing nitro group in the para position to the iodine atom in the benziodoxolone ring dramatically increases the rate of substitution. These observations are in agreement with the electronic requirements for internal nucleophilic substitution in the benziodoxole ring. A quantum‐chemical computational study of the possible reaction paths is in agreement with the observed effects of substituents on the reactivity of arylbenziodoxolones in this reaction.

Halogen bonds in 2,5-dihalopyridine-copper(ii) chloride complexes

In the (2,5-dihalopyridine)2·CuCl2complexes varying the C5-position halogens affects the halogen bonding properties so that the C5–X5⋯Cl–Cu halogen bonds follow the order F5 < Cl5 < Br5 < I5 when the substituent at 2-position is chlorine and Cl5 < Br5 < I5 when it is bromine.

Structural characterization, AC conductivity, optical properties and biochemical study of a new hybrid phosphate: Scavenger of free radicals

Single crystal of the hybrid compound [p-(F)C6H4NH3]6P6O18·2H2O has been grown with sizes up to 0.65 × 0.45 × 0.3 mm3 by the slow evaporation method. The crystal structure of this material was determined by single crystal X-ray diffraction. It crystallizes in the triclinic space group P 1¯ with the lattice parameters a = 10.16(3) Å, b = 15.87(3) Å, c = 16.36(4) Å, α = 80.93(2)°, β = 85.92(18)°, γ = 85.31(2)°, V = 2591.1(12) Å3 and Z = 2. Its crystal structure is a packing of alternated inorganic and organic layers parallel to (a, c) planes. The cohesion of the structure is essentially ensured by a hydrogen bonding network as well as electrostatic and Van Der Waals interactions and also F…F interactions so as to increase the stability of the 3D-network. The effect of the nature of the substituent in para-position with respect to amine group on obtained structures and on other studied properties was discussed. Crystal symmetry is confirmed by 31P MAS-NMR. Furthermore, IR characteristics and thermal analysis are given. The luminescent properties of this material have been carried out at room temperature based on UV absorption spectroscopy data. AC conductivity of this compound has been investigated by means of impedance spectroscopy measurements in the 303–383 K temperature range. The antioxidant study was determined, in vitro, using 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical and reducing power and with ascorbic acid as a control. X-rays structural results are correlated with electrical and antioxidant findings.

Exploring the pnicogen bond non-covalent interactions in 4-XPhNH2:PFnH3-n complexes (n = 1–3, X = H, F, CN, CHO, NH2, CH3, NO2 and OCH3)

Quantum chemical calculations were carried out to explore the effects of substituents in para position of aniline as well as phosphine on the strength of interactions in pnicogen-bonded (PB) complexes of the 4-XPhNH2:PFnH3-n (n=1–3 and X=H, F, CN, CHO, NH2, CH3, NO2 and OCH3). The P⋯N pnicogen bond strength in these complexes was examined at M06-2X/6–311++G(d,p), MP2/6–311++G(d,p), MP2/cc-pVDZ, CCSD/cc-pVDZ and MP2/aug-cc-pVTZ levels of theory. The dispersion corrected M06-2X-GD3, B2PLYP-GD3 and mPW2PLYP-GD2 functionals were also used to calculate the binding energies. The changes in the pnicogen bond strength due to the change of the substituents were well monitored by the changes in the interaction energy, structural parameters, natural charge, charge transfer, electron density topology, NMR chemical shielding and spin-spin coupling constants. The BSSE-corrected BEs change from 14.5 to 21.4kJmol−1 for the 4-XPhNH2:PF3, 21.5 to 30.5kJmol−1 for the 4-XPhNH2:PF2H and 24.2 to 33.1kJmol−1 for the XPhNH2:PFH2 complex at MP2/aug-cc-pVTZ level and 12.5 to 18.9kJmol−1 for the 4-XPhNH2:PF3, 17.4 to 26.5kJmol−1 for the 4-XPhNH2:PF2H and 18.9 to 26.5kJmol−1 for the XPhNH2:PFH2 complexes at MP2/6–311++G(d,p) level. For each PFnH3-n monomer, results demonstrated that the strength of the pnicogen bonds increases by introducimg electron-donating substituents in 4-XPhNH2 molecule, whereas a reverse situation was found upon introducing electron-accepting substituents. Natural bond orbital analysis confirmed that the charge transfer takes place from 4-XPhNH2 to PFnH3-n. Electron density properties based on atoms in molecules theory were also utilized to characterize the pnicogen bonds.

Tuning the redox potentials of ternary cobalt(III) complexes containing various hydroxamates

Abstract Sixteen cobalt(III) complexes incorporating one of the investigated 4N donor tripodal amines in the presence or absence of differently substituted hydroxamates have been synthesized and the effect of the nature of the N-donor, size of the chelates formed and the effect of the type of the substituent(s) at the hydroxamate moiety on the redox properties of the complexes have been studied. The crystal and molecular structures of the new complexes, [Co(uns-penp)(H 2 O)Cl]Cl 2 ·H 2 O ( 4 ), [Co(tren)(phebha)](ClO 4 ) 2 ( 11 ), [Co(tpa)(bha)](ClO 4 ) 2 ·C 2 H 5 OH·H 2 O ( 15 ) and [Co(tpa)(phebha)](ClO 4 ) 2 ( 16 ) have also been determined by single crystal X-ray diffraction method. Cyclic voltammetric (CV) results indicated the irreversible reduction of Co(III) in all the investigated complexes. Out of the four studied tripodal amines, abap was found to decrease the Co(III/II) reduction potential far below the region of bioreductants. Decreasing of two of the chains by one CH 2 in tren compared to abap resulted in less negative reduction potential of the corresponding complex. Further positive shift was observed by introducing two (uns-penp), and especially three (tpa) π-back-bonding pyridyl rings into the chains of tetramines. In agreement with literature results, the 3+ oxidation state of the central cobalt ion was found to be extremely stabilized in the ternary complexes containing the doubly deprotonated benzohydroximate, but the metal ion is significantly more reducible in the ternary complexes with mono-deprotonated benzohydroxamate/derivative ligands. Measurable effect was not found on the redox potential via introduction of chloro or nitro substituents in para position into the phenyl moiety of bha − (Cl-bha − and NO 2 -bha − ). Significant positive shift (ca. 200 mV) was obtained, however, when R N = H was replaced by a phenyl ring in phebha − therefore complexes with this latter ligand can be likely candidates for the in vitro releasing of hydroxamates with proven biological activity.

5-Aryl-1H-pyrazole-3-carboxylic acids as selective inhibitors of human carbonic anhydrases IX and XII

Inhibitory activity of a congeneric set of 23 phenyl-substituted 5-phenyl-pyrazole-3-carboxylic acids toward human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX and XII was evaluated by a stopped-flow CO2 hydrase assay. These compounds exerted a clear, selective inhibition of hCA IX and XII over hCAI and II, with Ki in two to one digit micromolar concentrations (4–50μM). Derivatives bearing bulkier substituents in para-position of the phenyl ring inhibited hCA XII at one-digit micromolar concentrations, while derivatives having alkyl substituents in both ortho- and meta-positions inhibited hCA IX with Kis ranging between 5 and 25μM. Results of docking experiments offered a rational explanation on the selectivity of these compounds toward CA IX and XII, as well as on the substitution patterns leading to best CA IX or CA XII inhibitors. By examining the active sites of these four isoforms with GRID generated molecular-interaction fields, striking differences between hCA XII and the other three isoforms were observed. The field of hydrophobic probe (DRY) appeared significantly different in CA XII active site, comparing to other three isoforms studied. To the best of our knowledge such an observation was not reported in literature so far. Considering the selectivity of these carboxylates towards membrane-associated over cytosolic CA isoforms, the title compounds could be useful for the development of isoform-specific non-sulfonamide CA inhibitors.