A new family of monothiooxalamides derived from 2-aminobenzimidazole was synthesized, and their structures were confirmed by 1H and 13C one-dimensional and 2D NMR experiments (COSY, HSQC, and HMBC). The antioxidant capacity was evaluated by free radical scavenging assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and the Fe(II) chelating ability. Our work group has previously reported the synthesis and antioxidant activity of monothiooxalamides derived from 2-aminopyridine (I). In this study, the in vitro hemolytic activity of compounds from the 2-aminopyridine (I) and 2-aminobenzimidazole (II) families was evaluated against human red blood cells (RBCs). The concentration at which monothiooxalamides showed no hemolytic activity was chosen to assess their ability to inhibit free radical-induced membrane damage in human RBCs, acute toxicity in brine shrimp, and in vivo toxicity against Drosophila melanogaster. Compounds with morpholine fragments (1g, 1h, 2g, and 2h) showed time- and concentration-dependent protective effects against radical-induced oxidative hemolysis. Moreover, they had the lowest acute toxicity in the brine shrimp lethality assay and a significant increase in chelating activity compared with the other molecules. In particular, monothiooxalamide 2g showed lower toxicity and can be considered for further biological screening and application trials.

New family monothiooxalamides containing pyridine moiety were synthesized. The structures of monoth-iooxalamides were confirmed by one-dimension NMR experiments H-1 and C-13, and 2D NMR (COSY, HSQC, and HMBC). In addition, antiproliferative activity was evaluated in human cancer cell lines. One com-pound showed antiproliferative effects against human tumor cell lines. Furthermore, the cytotoxic com-pound showed the ability to induce a Reactive Oxygen Species (ROS) production on the A2780-wt cell line. This study discarded the substitution pattern of non-active and allowed to identify the structure that could be used as a scaffold for the future design of monothiooxalamides with promising antipro-liferative capability. Moreover, the in vitro antioxidant activity was determined by DPPH center dot , ABTS center dot(+), FRAP, ORAC, and the Fe(II) chelating ability assays. Additionally, the antiradical potential was determined the-oretically employing Donor-Acceptor Maps (DAM), and the function was used to estimate the reactive regions involved in this process. (C) 2022 Elsevier B.V. All rights reserved.

Intramolecular charge transfer (ICT) effects are responsible for the photoluminescent properties of coumarins. Hence, optical properties with different applications can be obtained by ICT modulation. Herein, four 3-acetyl-2H-chromen-2-ones (1a–d) and their corresponding fluorescent hybrids 3- (phenylhydrazone)-chromen-2-ones (2a–d) were synthesized in 74–65% yields. The UV-Vis data were in the 295–428 nm range. The emission depends on the substituent in position C-7 bearing electron-donating groups. Compounds 1b–d showed good optical properties due to the D-π-A structural arrangement. In compounds 2a–d, there is a quenching effect of fluorescence in solution. However, in the solid, an increase is shown due to an aggregation-induced emission (AIE) effect given by the rotational restraints and stacking in the crystal. Computational calculations of the HOMO-LUMO orbitals indicate high absorbance and emission values of the molecules, and gap values represent the bathochromic effect and the electronic efficiency of the compounds. Compounds 1a–d and 2a–d are good candidates for optical applications, such as OLEDs, organic solar cells, or fluorescence markers.

The structures of thioethers I-III and the new amidic compounds 1(a-f)-3(a-f) derived from 2-mercaptobenzimidazole (MBZ) and cinnamic acids were confirmed by NMR and elemental analysis. Antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH●) radical scavenging assay and 2,2-azinobis (3-ethyl benzothiazoline-6-sulfonic acid) ABTS●+ radical cation decolorization method. Besides, donor-acceptor maps (DAM) and electrophilicity were calculated using DFT/B3LYP method with a 6-311G(d,p) basis set. MBZ, I-III and (1a-3a) compounds showed higher activity in vitro antioxidant assays, confirming with in silico studies that they are the best candidates. The findings found in antiradical activity suggest that these compounds could be promising in the development of new antitumor and antimicrobial agents. QSAR Molecular properties and topological descriptors of the synthesized compounds 1(a-f)-3(a-f) were calculated. The QSAR model indicates that the size and molecular shape are relevant for the antiradical activity for this family of compounds.

A new organic salt of metformin, an antidiabetic drug, and N,N′-(1,4-phenylene)dioxalamic acid, was mechanochemically synthesized, purified by crystallization from solution and characterized by single X-ray crystallography. The structure revealed a salt-type crystal hydrate composed of one dicationic metformin unit, two monoanionic units of the acid and four water molecules, namely H2Mf(HpOXA)2∙4H2O. X-ray powder, IR, 13C-CPMAS, thermal and BET adsorption–desorption analyses were performed to elucidate the structure of the molecular and supramolecular structure of the anhydrous microcrystalline mesoporous solid H2Mf(HpOXA)2. The results suggest that their structures, conformation and hydrogen bonding schemes are very similar. To the best of our knowledge, the selective formation of the monoanion HpOXA−, as well as its structure in the solid, is herein reported for the first time. Regular O(δ−)∙∙∙C(δ), O(δ−)∙∙∙N+ and bifacial O(δ−)∙∙∙C(δ)∙∙∙O(δ−) of n→π * charge-assisted interactions are herein described in H2MfA organic salts which could be responsible of the interactions of metformin in biologic systems. The results support the participation of n→π * charge-assisted interactions independently, and not just as a short contact imposed by the geometric constraint due to the hydrogen bonding patterns.

Four compounds derived from 2-hydroxy and 2-mercaptobenzimidazole were synthesized and characterized by FT-IR spectroscopy, nuclear magnetic resonance and elemental analysis. Two of the resulting compounds –diethyl 2-oxo-1H benzo[d]imidazole-1,3(2H)-dicarboxylate and diethyl 2-thioxo-1H benzo[d]imidazole-1,3(2H)-dicarboxylate– were crystallized and analyzed by X-ray diffraction. The former presented intermolecular interactions of bidentate hydrogen-bonds and the formation of R22(10) rings via C–H⋯OC, resulting in a stacking arrangement while the latter had a zig-zag arrangement due to the intermolecular aromatic interaction C–H⋯OC. A computational conformational study was made to support and explain the resulting structures stabilities. Furthermore, a QTAIM analysis was performed to study the nature of the intramolecular 1,5-type O⋯O and S⋯O interactions.

The compound 2-aryl-2,3-dihydro-4H- [1,3]thiazino[3,2-a]benzimidazol-4-one (C16H12N2OS) (III) was synthesized. The compound crystallized in a monoclinic crystal system with P21/c space group as revealed by mono-crystal X-ray diffraction. The X-ray analysis and density functional theory complementary calculations showed that noncovalent C–H···π interactions between the benzimidazole system and the thiazine ring form a dimerization along the direction of the b axes, additionally π···π interactions were found between the benzene rings. The C12, in the thiazine ring, has a distortion angle (41.69°) respect to the plane of benzimidazole. The intermolecular interactions in the crystal structure were quantified and analyzed using Hirshfeld surface analysis. The predominant interaction within the crystalline structure was found to be H⋯H interaction. On the other hand, antioxidant activity of the C16H12N2OS system was studied using the DPPH and ABTS+ assay. Using the energy profile for the reaction of DPPH with III it was demonstrated that the antioxidant activity is carried out through HAT (H12) mechanism where conjugation of the radical can occur between the C12 of the thiazine ring and the aromatic ring, this was confirmed by a H function calculation. The importance of this study focuses on the promising range of biological activities and molecular characteristics of the synthesized compound (III).

A new cocrystal salt of metformin, an antidiabetic drug, and N,N’-(1,4-phenylene)dioxalamic acid, was synthesized by mechanochemical synthesis, purified by crystallization from solution and characterized by single X-ray crystallography. The structure revealed a salt-type cocrystal composed of one dicationic metformin unit, two monoanionic units of the acid and four water molecules namely H2Mf(HpOXA)2∙4H2O. X-ray powder, IR, 13C-CPMAS, thermal and BET adsorption-desorption analyses were performed to elucidate the structure of the molecular and supramolecurar structure of the anhydrous microcrystalline mesoporous solid H2Mf(HpOXA)2. The results suggest that their structures, conformation and hydrogen bonding schemes are very similar between them. To the best of our knowledge, the selective formation of the monoanion HpOXA⁻, as well as its structure in the solid, is herein reported for the first time. Regular O(-)∙∙∙C(), O(-)∙∙∙N+ and bifacial O(-)∙∙∙C()∙∙∙O(-) of n→* charge-assisted interactions are herein described in H2MfA cocrystal salts which could be responsible of the interactions of metformin in biologic systems. The results, support the participation of n→* charge-assisted interactions independently, and not just as a short contact imposed by the geometric constraint due to the hydrogen bonding patterns.

In this investigation, the reaction of 2-dithiomethylcarboimidatebenzothiazole with a series of six chiral amino-acids was studied. The reaction proceeds through the isolable sodium salt of SMe-isothiourea carboxylates as intermediates, whose reaction with methyl iodide in stirring DMF as solvent affords SMe-isothiourea methyl esters. The presence of water in the reaction leads to the corresponding urea carboxylates as isolable intermediates, whose methyl esters were obtained. Finally, the urea N-methyl amide derivatives were isolated when SMe-isothiourea or urea methyl esters were reacted with methylamine in the presence of water. The structures of synthesized compounds were established by 1H and 13C nuclear magnetic resonance and the structures of SMe-isothiourea methyl esters derived from (l)-glycine, (l)-alanine, (l)-phenylglycine, and (l)-leucine, by X-ray diffraction analysis. This methodology allows to functionalize 2-aminobenzothiazole with SMe-isothiourea, urea, and methylamide groups derived from chiral amino acids to get benzothiazole derivatives containing coordination sites and hydrogen bonding groups. Further research on the biological activities of some of these derivatives is ongoing.

Benzimidazole (BI) and derivatives are interesting because several of these compounds have been found to have a diversity of biological activities with clinical applications. In view of their importance, the synthesis of BI and its derivatives is still considered as a challenge for synthetic chemists. Examples of compounds used in medicinal chemistry containing BI, as important nucleus, are Astemizole (antihistaminic), Omeprazole (antiulcerative) and Rabendazole (fungicide), some of these compounds have the 2- aminobenzimidazole (2ABI) as base nucleus. The structure of 2ABI derivatives contains a cyclic guanidine moiety, which is interesting because of its free lone pairs, labile hydrogen atoms and planar delocalized structure. The delocalized 10-π electron system and the extension of the electron conjugation with the exocyclic amino group, in 2ABI, making these heterocycles to have amphoteric character. The 2ABI has been used as building blocks for the synthesis of several BI derivatives as medicinally important molecules. On these bases, herein, we present a bibliographic review concerning the recent methodologies used in the synthesis of 2ABIs, including the substituted ones.

New tributyl-, dibutyl-and diphenyl-tin(IV) complexes derived from ibuprofen and cinnamic acids were synthesized. All compounds were structurally characterized by FT-IR, multinuclear H-1, C-13, F-19 and Sn-119 NMR and corroborated by 2D spectra. The NMR data in CDCl3 revealed several hexacoordinated compounds with octahedral geometry. Moreover, in DMSO-d(6) some of these complexes switched to heptacoordination with a pentagonal-bipyramidal geometry due to the inclusion of a solvent's molecule; their Sn-119 signals moved up field by around 58 ppm compared to their chemical shifts in non-coordinated solvent CDCl3. The structural results were supported by Density Functional Theory (DFT) computational calculations. In addition, a docking study was performed to evaluate the ability of ligands to interact within the active site of cyclooxygenases (COX-1 and COX-2). Docking results showed a possible binding of stannoxanes theoretically more selective towards COX-2 than ibuprofen. (C) 2018 Elsevier B.V. All rights reserved.

There are many chronic diseases related with inflammation. The chronic inflammation can produce other problems as cancer. Therefore, it is necessary to design drugs with better anti-inflammatory activity than those in the clinic. Likewise, these could be used in chronic treatments with minimum adverse effects. The amide or ester functionality in combination with the insertion of a silyl alkyl moiety is able to improve some drug properties. In this context, the evaluation of a group of silicon containing ibuprofen derivatives (SCIDs) as antioxidants and anti-inflammatory agents is reported. Antioxidant activity was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH⨪), 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS•+) and the Fe(II) chelating ability methods. The anti-inflammatory activity was determined by using the carrageenan induced rat paw edema. The gastrotoxic profile of the SCIDs that displayed significant anti-inflammatory activity was determined by the indomethacin induced ulceration method. The SCIDs performed better than ibuprofen as chelating agents for Fe(II) and as scavengers for the free radicals DPPH• and ABTS•+. On the anti-inflammatory test, compound 4a inhibited the edema up to 87%, while 4d & 10b achieved significant inflammation inhibition at a lower effective dose 50 (ED50) than ibuprofen´s. None of the SCIDs endowed with anti-inflammatory activity, showed significant gastrotoxic effects with respect to those displayed by ibuprofen. Based on the experimental results and aided by the theoretical docking approach, it was possible to rationalize how the SCIDs may bind to cyclooxygenase isoforms and helped to explain their reduced gastrotoxicity. The evaluated effects were improved in SCIDs with respect to ibuprofen.

The synthesis and structural characterization of novel amine-borane adducts of ibuprofen derivatives are presented. The changes of the electron density on the carbonyl and pyridine ring after formation of NBH3, NBF3, and N-CH3+ have been confirmed by H-1, B-11, C-13, and F-19 NMR, further supported by homonuclear and heteronuclear correlations. Moreover, electrostatic interactions H+-F and the nonclassical H+-H were identified by NMR spectra. The analysis of the resulting molecular structures offered insights on the 2-aminopyridine NB adducts. The NBH3 adduct formed a single molecular arrangement, both in C6D6 and CDCl3. The same behavior was observed for the NBF3 adduct in CDCl3. However, two conformers of this adduct were detected in C6D6. All adduct geometries were corroborated by density functional theory computational calculations.

Herein we report the synthesis and structural study of ten new tin compounds derived from the polyfunctional and optically active pro-ligand: 2-phenyl-2-(p-tosylsuphonamino)acetic acid (1). Reactions of the sodium carboxylate of compound 1 with SnMe2Cl2; SnPh2Cl2, SnMe3Cl, SnPh3Cl and that of 1 with nBu2SnO in benzene were investigated. Structures of the reaction products {chloro(dimethyl)tin [(S) 2-phenyl-2-(p-tolylamino)]acetate (2), trimethyltin [(S) 2-phenyl-2-(p-tolylamino)]acetate (3), triphenyltin (S) 2-phenyl-2-(4-methylphenylamino)acetate (4), dimethyltin bis-[2-phenyl-2-(p-tolylamino) acetate] (5), chlorophenyltin bis-[2-phenyl-2-(p-tolylamino)acetate] (6), diphenyltin bis-[2-phenyl-2-(p-tolylamino)acetate] (7) and aqua-dinbutyltin bis-[2-phenyl-2-(p-tolylamino) acetate] (8)} were determined by NMR and high resolution mass spectrometry. Two crystals from compound 3 (3a and 3b), one from aqua-diphenyltin bis-[2-phenyl-2-(p-tolylamino)acetate] (9) and one from dinbutyl-distannoxane tetra[2-phenyl-2-(p-tolylamino)acetate] (10) were analysed by X-ray diffraction. The new compounds are hypervalent; 2–4 are pentacoordinated, 5–7 are hexacoordinated whereas 8 and 9 are heptacoordinated. Theoretical study of compounds 2, 3, and the model compounds: dimethyltin bis-acetate, diphenyltin bis-acetate and their water complexes was performed by B3LYP/LANL2DZ base calculations, particularly O⋯O interaction through the space.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

COX-2 is a widely studied biological target, since its activity is directly related to the inflammation response. The design of COX-2 selective inhibitors is an ongoing topic in drug design. We performed a quantitative structure–activity relationship and docking studies over a series of benzenesulfonamide derivatives on their inhibition towards COX-1 and COX-2, in order to rationalize their selectivity towards COX-2. Constitutional, topological and molecular property descriptors for the QSAR models and molecular docking calculations were employed. The mathematical model highlighted that lipophilic character and size are the most important features for COX-2 inhibition by benzenesulfonamides. A second QSAR model revealed that the dipole moment, the number of hydrogen bond donors and lipophilicity descriptors of benzenesulfonamides are crucial for their binding to COX-1. Moreover, artificial neural networks were employed to improve the prediction power of the COX-1 inhibition QSAR model. In this sense, we proposed new selective potential inhibitors by introducing different halogens into the benzenesulfonamide scaffold, improving their interactions with key residues of COX-2.

Two new molecular structures, namely 1,3-bis(trimethylsilyl)-1H-benzimidazole-2(3H)-thione, C13H22N2SSi2, (2), and 1-trimethylsilyl-1H-benzimidazole-2(3H)-thione, C10H14N2SSi, (3), are reported. Both systems were derived from 1H-benzimidazole-2(3H)-thione. Noncovalent C-H···π interactions between the centroid of the benzmidazole system and the SiMe3 groups form helicoidal arrangements in (2). Dimerization of (3) results in the formation of R2(2)(8) rings via N-H···S interactions, along with parallel π-π interactions between imidazole and benzene rings.

The synthesis and characterisation of new silicon-containing amides and esters derived from ibuprofen is reported. These compounds were tested against nuclear transcription factor κβ (NF-κβ). Higher inhibition values than those of ibuprofen were achieved by the new amides 10a–10d; ester derivatives did not show inhibitory activity. The cytotoxicity of these new derivatives was screened; none of them displayed significant toxicity at the screened doses. A molecular docking calculation on IKKβ (an enzyme related to NF-κβ activation) was carried out and the results showed that the amides interact better than ibuprofen with key residues, which are important to the inhibition of IKKβ.

Here we explore in the Density Functional Theory (DFT) framework the antiradical activity of picolinic (PA), nicotinic (NA) and isonicotinic (INA) acids and a group of derivative stannoxanes of the type RC(O)OSnX3. Using the single charge transfer model proposed by Gázquez et al. (electrodonating ω− and electroaccepting ω+ powers), a Donor Acceptor Map (DAM) was employed to classify them as good or bad antiradicals. In the case of acids, an antiradical activity behavior was measured for each bond position of the –COOH functional group at the pyridine ring. For esters, antiradical activity was calculated considering three types of ligands: n-butyl, phenyl and the above acids. Esters showed a better antiradical behavior as electron donors than their corresponding acids. Two esters derived from picolinic acid showed a good donor index (Rd), which was closed to Rd of vitamin C, all above in their neutral form. In this assessment, the analytic Fukui function isosurface f− was included in order to determinate those regions of our molecules where it is most likely to occur the interaction with a free radical. The Fukui function f− was located mainly at the N atom of the pyridine ring for the three acids and most of the esters.