Role of Substituent Position in Coumarin Derivatives during their Interaction with TiO2 Nano Particles.

The effect of position of benzo group in coumarin derivatives, 5,6 benzo-4-azidomethyl coumarin (5BAMC) and 7,8 benzo-4-azidomethyl coumarin (7BAMC) during their interaction with TiO2 nanoparticles in ethyl acetate, tetrahydrofuran, butan-1-ol and acetonitrile solvents has been studied using different spectroscopic methods and electrochemical analysis. Benesi-Hildebrand plots indicate that nature of interaction between 7BAMC and TiO2 is 1:2 in solvent with low dielectric constant whereas for 5BAMC and TiO2, it is 1:1 in all the solvents. From the fluorescence quenching study and binding equilibria analysis, it is observed that interaction between 5BAMC and TiO2 depends on the dielectric constant of the solvent. Time resolved quenching study reveals that quenching is dynamic for 5BAMC in solvent with high dielectric constant. Whereas for 7BAMC, it is dynamic in solvent with low dielectric constant. Hence the nature of interaction of these two coumarin derivatives with TiO2 NPs is different. From electrochemical analysis, it is observed that, free energy change for electron transfer is more negative for 5BAMC-TiO2 compared to 7BAMC-TiO2 therefore quenching is more efficient for 5BAMC-TiO2 compared to 7BAMC-TiO2 system, which is also confirmed from fluorescence quenching studies. Non-radiative energy transfer rate is more than radiative energy transfer rate for both the systems according to FRET study.

A click chemistry approach for the synthesis of cyclic ureido tethered coumarinyl and 1-aza coumarinyl 1,2,3-triazoles as inhibitors of Mycobacterium tuberculosis H37Rv and their in silico studies.

Nucleoside bases like uracil, pharmacophoric triazoles and benzimidazolones have been used during the present study to design molecular matrices for antitubercular activity, employing Click Chemistry. Click triazoles 4/7/10 have been obtained by the reaction of 4-(Azidomethyl)-2H-chromen-2-ones/quinolin-2(1H)-ones 3 and propargyl ethers 2/6/9 derived from theophylline/6-methyl uracil/2-benzimidazolone respectively. In addition to spectral data structures have been confirmed by single crystal X-ray diffraction studies in case of uracil bis alkyne (6) and theophylline mono triazole (4c). Theophylline linked mono triazoles, 4(a-d) and 6-methyl uracil linked bis triazoles, 7(a-e) have been found to inhibit Mycobacterium tuberculosis H37Rv with MIC values in the range 55.62-115.62 µM. Benzimidazolone bis triazoles, 10(a-n) showed better activity with MIC in the range 2.33-18.34 µM. Molecular modeling studies using Surflex-Dock algorithm supported our results.

Crystal structure of 4-(4b,8a-di-hydro-9H-pyrido[3,4-b]indol-1-yl)-7-methyl-2H-chromen-2-one.

The title compound, C21H14N2O2, was prepared by Pictet-Spengler cyclization of tryptamine and 4-formyl coumarin. In the mol-ecule, the dihedral angle between the mean planes of the coumarin and ß-carboline ring systems is 63.8 (2)°. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming chains along the b-axis direction. Within the chains, there are a number of offset π-π inter-actions present [shortest inter-centroid distance = 3.457 (2) Å].

One pot Click chemistry: A three component reaction for the synthesis of 2-mercaptobenzimidazole linked coumarinyl triazoles as anti-tubercular agents.

2-Propargylthiobenzimidazole 1, 4-bromomethyl coumarins/1-aza-coumarins 2/3 and sodium azide have been reacted in one pot under Click chemistry conditions to give exclusively 1,4-disubstituted triazoles 5a-n. Anti-tubercular assays against M. tuberculosis (H37Rv) coupled with in silico molecular docking studies indicated that dimethyl substituents 5c and 5d showed promising activity with higher C-score values.

Rhodium-Catalyzed Regioselective Synthesis of Isocoumarins through Benzothiadiazine-Fused Frameworks.

An unprecedented two-step, one-pot synthesis of benzimidazothiadiazine 5,5-dioxides is presented. Reaction condition based regioselectivity has been achieved where fused benzimidazo[1,2-b][1,2,4]thiadiazines are exclusively formed under thermal conditions, whereas benzimidazo[2,1-c][1,2,4]thiadiazines were created only under microwave irradiation. The salient features of this protocol include a regioselective sulfonylation of 2-aminobenzimidazole with o-halo sulfonyl chlorides followed by N-C bond formation. The acid forms of these fused regioisomers have been used to introduce novel guanidine-containing isocoumarin frameworks.

A click chemistry approach for the synthesis of mono and bis aryloxy linked coumarinyl triazoles as anti-tubercular agents.

A series of mono and bis-triazole coumarin hybrids 6a-u and 9a-f respectively have been synthesized using 4-(azidomethyl)-2H-chromen-2-ones 5a-i and aryl propargyl ethers 2a-c/8 employing Click chemistry modified protocol for Azide-Alkyne cycloadditions(CuAAC). Anti-tubercular screening showed moderate activity for mono aryloxy compounds 6a-u with MIC 50-100 µg/mL, whereas the bis compounds 9a-f were more effective with MICs between 0.2 and 12.5 µg/mL. Molecular modeling and 3D-QSAR measurements using CoMFA and Topomer CoMFA further supported the observed results. The bis compound 9b showed excellent activity with MIC value as low as 0.2 µg/mL.

Crystal structure of 6,6'-dimethyl-2H,2'H-3,4'-bichromene-2,2'-dione.

In the title compound, C20H14O4, the dihedral angle between the two coumarin ring systems is 52.37 (19)°, showing a gauche arrangement across the C-C bond which links the two units. The carbonyl groups of the two coumarin units adopt an s-trans arrangement. In the crystal, pairs of C-H⋯O hydrogen bonds and π-π inter-actions [centroid-centroid distance = 3.631 (2) Å] connect the mol-ecules into inversion dimers.

Synthesis, biological evaluation and docking studies of 4-aryloxymethyl coumarins derived from substructures and degradation products of vancomycin.

Two series of 4-aryloxymethyl coumarins derived from the reaction of 4-bromomethyl coumarins with ethyl gallate and ethyl ester of N-Benzoyl tyrosine have been synthesized. Gallate ethers 3a-3g and tyrosine derivatives 4e-4j were most effective against Entercoccus faecalis. They were also found to be effective against Aspergillus niger and Candida albicans. Comparative docking studies with novobiocin have indicated better binding ability and higher 'C' score values than novobiocin.

4-{[Bis(2-hy-droxy-eth-yl)amino]-meth-yl}-6-meth-oxy-2H-chromen-2-one.

In the title compound, C(15)H(19)NO(5), an intra-molecular O-H⋯O hydrogen bond links the hy-droxy-ethyl side chains, forming a seven-membered ring. In the crystal, mol-ecules are linked into chains via O-H⋯O hydrogen bonds along the b axis. Further, mol-ecules are linked by weak inter-molecular C-H⋯O and π-π stacking inter-actions [centroid-centroid distance = 3.707 (4) Å].

Click chemistry approach for bis-chromenyl triazole hybrids and their antitubercular activity.

1,4-Disubstituted bis-chromenyl triazole hybrids 5a-m have been synthesized in a three-step reaction sequence from 4-(bromomethyl)-2H-chromen-2-ones 3a-m. The intermediate azides 4a-m underwent a regioselective 1,3-dipolar cycloaddition with a 2H-chromen-2-one linked acetylenic dipolarophile in the presence of Cu (II)/ascorbate/water/n-butanol reaction medium. Three compounds 5h-j exhibited 6.25 µg/mL MIC against M. tuberculosis. Among the compounds screened for antifungal activity, lowest MIC of 6.25 µg/mL was observed for 5c against A. niger that also exhibited DNA cleavage observed by agarose gel electrophoresis. All the compounds were moderately active against both Gram-positive and Gram-negative bacterial strains. The cytotoxic effect of potent compounds on normal cells (V79 and HBL100) was assessed by MTT assay.

6-Chloro-4-(4-methyl-phen-oxy-meth-yl)-2H-chromen-2-one.

In the title compound, C(17)H(13)ClO(3), the coumarin and phen-oxy moieties are essentially co-planar, making a dihedral angle of 1.99 (7)°. The phen-oxy moiety is oriented anti-periplanar with respect to the coumarin ring as indicated by the C-C-O-C angle of -179.97 (16)°. In the crystal, the sheet-like packing is stabilized by inter-molecular C-H⋯O and C-H⋯Cl hydrogen bonds.

Effect of solvent polarity on the fluorescence quenching of biologically active 5BAMC by aniline in binary solvent mixtures.

The fluorescence quenching of 5, 6-benzo-4-azidomethyl coumarin (5BAMC) by aniline have been carried in different solvent mixtures of benzene (BN) and acetonitrile (AN) at room temperature by steady state fluorescence measurements. The quenching is found to be appreciable and a positive deviation from linearity was observed in the Stern-Volmer plot for the fluorophore in all the solvent mixtures. Various parameters for the quenching process have been determined using the extended S-V equation and have been found to be dependent on the solvent polarity. Further, with the use of finite sink approximation model, it is concluded that the bimolecular reactions quenching reactions are diffusion limited, and the distance parameter R' and mutual diffusion coefficient D are estimated independently.

Synthesis and antimicrobial studies on novel sulfonamides containing 4-azidomethyl coumarin.

A series of new and novel coumarin-6-sulfonamides with a free C4-azidomethyl group have been synthesized as antimicrobials in three steps starting from 7-methyl-4-bromomethylcoumarin 1. The reaction of 1 with chlorosulfonic acid was found to yield the corresponding 6-sulfonylchloride 2, which when treated with sodium azide led to intermediate 3. The title sulfonamides 5a-y were obtained from the reaction of 3 with various aromatic amines 4 in refluxing benzene. The chemical structures of the compounds were elucidated by IR, NMR and LC-MS spectral data. All the synthesized compounds have been screened for their in vitro anti-bacterial and anti-fungal activities. Some of the compounds have been found to be active against both bacterial species at a concentration of 1 microg/mL.

4-Azido-methyl-7-methyl-2-oxo-2H-chromene-6-sulfonyl azide.

In the title compound, C(11)H(8)N(6)O(4)S, the plane of the coumarin aromatic ring is twisted by 17.2 (2)° with respect to the plane of the azide group bound to the methyl-ene substituent, whereas it is twisted by 83.2 (2)° to the plane of the azide attached to the sulfonyl group. The crystal structure is stabilized by weak C-H⋯O inter-actions, leading to the formation of dimers with R(2) (2)(12) graph-set motifs. These dimers are further linked by weak S-O⋯π and π-π contacts [centroid-centroid distance = 3.765 (2) Å], leading to the formation of a layered structure.

4-Bromo-methyl-6-meth-oxy-2H-chromen-2-one.

The structure of the title coumarin derivative, C(11)H(9)BrO(3), is stabilized by weak inter-molecular C-H⋯O hydrogen bonds.

4-Bromo-methyl-7,8-dimethyl-coumarin.

In the title mol-ecule, C(12)H(11)BrO(2), all non-H atoms with the exception of the Br atom are essentially coplanar (r.m.s. deviation = 0.018 Å). The C-Br bond is inclined by 80.17 (12)° to this plane. The crystal structure is stabilized by weak C-H⋯O hydrogen bonds.

Estimation of dipole moments of some biologically active coumarins by solvatochromic shift method based on solvent polarity parameter, E(T)(N).

The electronic absorption and fluorescence spectra of three newly synthesized coumarin derivatives viz., 4-(5-methyl-3-furan-2-yl-benzofuran-2-yl)-7-methyl-chromen-2-one (MFBMC), 4-(5-chloro-3-furan-2-yl-benzofuran-2-yl)-6-methyl-chromen-2-one (ClFBMC) and 4-(5-methyl-3-phenyl-benzofuran-2-yl)-6-chloro-chromen-2-one (MPBClC) have been recorded at room temperature (296 K) in solvents of different polarities. The effects of the solvents upon the spectral properties are discussed. Solvatochromic correlations were used to estimate the ground-state (mu(g)) and excited-state (mu(e)) dipole moments. The excited-state dipole moments for all the three molecules are found to be larger than their corresponding ground-state dipole moments. Further, the changes in dipole moment (Delta mu) were calculated both from solvatochromic shift method and on the basis of microscopic empirical solvent polarity parameter (E(T)(N)), and the values are compared.

4-Bromo-methyl-7-methyl-6,8-dinitro-coumarin.

The crystal structure of the title compound, C(11)H(7)BrN(2)O(6), establishes the substitution positions of the nitro groups from the nitration reaction of 7-methyl-4-bromo-methyl coumarin. The mean planes of the nitro groups form dihedral angles of 43.9 (8) and 52.7 (10)° with the essentially planar [maximum deviation 0.031 (6) Å] benzopyran ring system.

1,3-Bis(hydroxy-meth-yl)benzimidazolin-2-one.

The title compound, C(9)H(10)N(2)O(3), crystallizes with one and a half mol-ecules in the asymmetric unit, one lying on a general position and the other on a twofold rotation axis. The dihedral angle between the two independent benzimidazole ring systems is 18.96 (5)°. In the crystal, mol-ecules are linked into a three-dimensional network by O-H⋯O hydrogen bonding involving N-hydroxy-methyl and carbonyl groups, and C-H⋯O hydrogen bonds.

Parallel synthesis of 2-sulphanylated bis-benzimidazoles on soluble polymer support.

A well-sustained multistep synthetic protocol has been designed for the PEG-functionalized aromatic acid amide to generate a molecular library of 2-alkylthio bis-benzimidazoles. An attempted synthesis of benzimidazole-2-thiol in dichloromethane has led to S-chloromethyl methyl sulfides, mimicking bacterial enzymatic systems. Regioselective S-alkylation was brought about under controlled conditions using a mild base at room temperature. The polymer-free compounds, 2-sulfanylated bisbenzimidazoles, were obtained in high yields and high purities. Chemical shift changes in proton and carbon NMR have been employed to monitor the progress of the reaction steps and to prove the site of S-alkylation, respectively.