In vitro assessment of antimicrobial, antioxidant, and cytotoxic properties of Saccharin-Tetrazolyl and-Thiadiazolyl derivatives: the simple dependence of the pH value on antimicrobial activity

The antimicrobial, antioxidant, and cytotoxic activities of a series of saccharin-tetrazolyl and -thiadiazolyl analogs were examined. The assessment of the antimicrobial properties of the referred-to molecules was completed through an evaluation of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against Gram-positive and Gram-negative bacteria and yeasts. Scrutiny of the MIC and MBC values of the compounds at pH 4.0, 7.0, and 9.0 against four Gram-positive strains revealed high values for both the MIC and MBC at pH 4.0 (ranging from 0.98 to 125 µg/mL) and moderate values at pH 7.0 and 9.0, exposing strong antimicrobial activities in an acidic medium. An antioxidant activity analysis of the molecules was performed by using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, which showed high activity for the TSMT (N-(1-methyl-2H-tetrazol-5-yl)-N-(1,1-dioxo-1,2-benzisothiazol-3-yl) amine, 7) derivative (90.29% compared to a butylated hydroxytoluene positive control of 61.96%). Besides, the general toxicity of the saccharin analogs was evaluated in an Artemia salina model, which displayed insignificant toxicity values. In turn, upon an assessment of cell viability, all of the compounds were found to be nontoxic in range concentrations of 0-100 µg/mL in H7PX glioma cells. The tested molecules have inspiring antimicrobial and antioxidant properties that represent potential core structures in the design of new drugs for the treatment of infectious diseases.Funding Agency Portuguese Foundation for Science and Technology UID/QUI/00100/2019 UID/MULTI/04326/2019 -CCMAR Portuguese Foundation for Science and Technology SFRH/BPD/99851/2014 IST-ID/115/2018info:eu-repo/semantics/publishedVersio

Carbenic nitrile imines: Properties and reactivity

Structures and properties of nitrile imines were investigated computationally at B3LYP and CCSD(T) levels. Whereas NBO analysis at the B3LYP DFT level invariably predicts a propargylic electronic structure, CCSD(T) calculations permit a clear distinction between propargylic, allenic, and carbenic structures. Nitrile imines with strong IR absorptions above ca. 2150 cm-1 have propargylic structures with a CN triple bond (RCNNSiMe 3 and R2BCNNBR2), and those with IR absorptions below ca. 2150 cm-1 are allenic (HCNNH, PhCNNH, and HCNNPh). Nitrile imines lacking significant cumulenic IR absorptions at 1900-2200 cm -1 are carbenic (R-(C:)-N=N-R′). Electronegative but lone pair-donating groups NR2, OR, and F stabilize the carbenic form of nitrile imines in the same way they stabilize "normal" singlet carbenes, including N-heterocyclic carbenes. NBO analyses at the CCSD(T) level confirm the classification into propargylic, allenic, and carbenic reactivity types. Carbenic nitrile imines are predicted to form azoketenes 21 with CO, to form [2+2] and [2+4] cycloadducts and borane adducts, and to cyclize to 1H-diazirenes of the type 24 in mildly exothermic reactions with activation energies in the range 29-38 kcal/mol. Such reactions will be readily accessible photochemically and thermally, e.g., under the conditions of matrix photolysis and flash vacuum thermolysis

Structural and functional insights into asymmetric enzymatic dehydration of alkenols

The asymmetric dehydration of alcohols is an important process for the direct synthesis of alkenes. We report the structure and substrate specificity of the bifunctional linalool dehydratase isomerase (LinD) from the bacterium Castellaniella defragrans that catalyzes in nature the hydration of β-myrcene to linalool and the subsequent isomerization to geraniol. Enzymatic kinetic resolutions of truncated and elongated aromatic and aliphatic tertiary alcohols (C5-C15) that contain a specific signature motif demonstrate the broad substrate specificity of LinD. The three-dimensional structure of LinD from Castellaniella defragrans revealed a pentamer with active sites at the protomer interfaces. Furthermore, the structure of LinD in complex with the product geraniol provides initial mechanistic insights into this bifunctional enzyme. Site-directed mutagenesis confirmed active site amino acid residues essential for its dehydration and isomerization activity. These structural and mechanistic insights facilitate the development of hydrating catalysts, enriching the toolbox for novel bond-forming biocatalysis

Photochemistry and Vibrational Spectra of Matrix-Isolated 5-Ethoxy-1-Phenyl-1H-Tetrazole

A combined matrix isolation FT-IR and theoretical DFT(B3LYP)/6-311++G(d,p) study of the molecular structure and photochemistry of 5-ethoxy-1-phenyl-1H-tetrazole (5EPT) was performed. A new method of synthesis of the compound is described. Calculations show three minima, very close in energy and separated by low-energy barriers (less than 4 kJ mol-1), in the ground-state potential energy profile of the molecule. The method of matrix isolation enabled the reduction of the number of populated conformational states in the experiment at low temperature due to the effect known as conformational cooling. As a result, the spectrum of the as-deposited matrix of 5EPT closely matches that of the most stable conformer predicted theoretically, pointing to the existence of only this conformer in the low-temperature matrixes. In this structure, the dihedral angle between the two rings, phenyl and tetrazole, is ca. 30°, whereas the ethyl group stays nearly in the plane of the tetrazole ring and is as far as possible from the phenyl group. In situ UV irradiation (λ > 235 nm) of the matrix-isolated 5EPT induced unimolecular decomposition, which led mainly to production of ethylcyanate and phenylazide, this later compound further reacting to yield, as final product, 1-aza-1,2,4,6-cycloheptatetraene. Anti-aromatic 3-ethoxy-1-phenyl-1H-diazirene was also observed experimentally as minor photoproduct, resulting from direct extrusion of molecular nitrogen from 5EPT. This species has not been described before and is now characterized by infrared spectroscopy for the first time

Solvent-free oxidation of benzyl alcohols catalysed by a tetrazole-saccharinate Zn(II) complex under microwave radiation: the role of the ligand and the reaction mechanism

Herein we present an efficient methodology for the microwave-assisted peroxidative oxidation of benzyl alcohols to the corresponding aldehydes by using a novel and stable tetrazole-saccharinate zinc(II) catalyst, along with some insights into the reaction mechanism. This methodology is distinguished by the use of easily available and cheap reagents on the genesis of the zinc catalyst, mild reaction conditions, very short reaction periods (5-20 min) and no need to add an organic solvent. Furthermore, the use of TBHP (70%. aq.) as oxidizing agent turn this protocol a convenient one for benzyl alcohol oxidation in yields up to 98%. (C) 2020 Elsevier B.V. All rights reserved.Centro de Quimica Estrutural [UIDB/00100/2020]Center of Marine Sciences (CCMAR) [DID/MULTI/04326/2019]FCT Portuguese Foundation for Science and Technology European Commission [IST-ID/115/2018]info:eu-repo/semantics/publishedVersio

Photochemistry of 5-allyloxy-tetrazoles: steady-state and laser flash photolysis study

The photochemistry of three 5-allyloxy-tetrazoles, in methanol, acetonitrile and cyclohexane was studied by product analysis and laser flash photolysis. The exclusive primary photochemical process identified was molecular nitrogen elimination, with formation of 1,3-oxazines. These compounds were isolated in reasonable yields by column chromatography on silica gel and were fully characterized. DFT(B3LYP)/6-31G(d,p) calculations predict that these 1,3-oxazines can adopt two tautomeric forms (i) with the NH group acting as a bridge connecting the oxazine and phenyl rings and (ii) with the –N bridge and the proton shifted to the oxazine ring. Both tautomeric forms are relevant in the photolysis of oxazines in solution. Secondary reactions were observed, leading to the production of phenyl vinyl-hydrazines, enamines, aniline and phenyl-isocyanate. Transient absorption, detected by laser flash photolysis, is attributed to the formation of triplet 1,3-biradicals generated from the excited 5-allyloxy-tetrazoles. The 1,3-biradicals are converted to 1,6-biradicals by proton transfer, which, after intersystem crossing, decay to generate the products. Solvent effects on the photoproduct distribution and rate of decomposition are negligible

UV-induced photochemistry of matrix-isolated 1-phenyl-4-allyl-tetrazolone

The photochemistry and molecular structure of 1-phenyl-4-allyl-tetrazolone (PAT) was studied by FT-IR matrix isolation spectroscopy and DFT(B3LYP)/6-311++G(d,p) calculations. The spectrum of matrix-isolated PAT monomers agrees well with the sum spectrum of three conformers predicted theoretically. UV irradiation (λ > 235 nm) of matrix-isolated PAT induces three types of photofragmentation: (1) production of phenylazide and allyl-isocyanate, with phenylazide then losing N2 to yield 1-aza-1,2,4,6-cycloheptatetraene; (2) formation of phenyl-isocyanate and allylazide; (3) N2 elimination leading to formation of 1-allyl-2-phenyldiaziridin-3-one; this compound partially reacts further to form 1-allyl-1H-benzoimidazol-2(3H)-one. The observed photochemistry of the matrix-isolated PAT is distinct from the preferred photochemical fragmentation in solution, where 3,4-dihydro-3-phenylpyrimidin-2(1H)-one is produced as the primary photoproduct