Benzotriazole Derivatives Research Articles

Synthesis and Spectral Characterization of Derivatives of Benzotriazole and Piperidine

Synthesis and Spectral Characterization of Derivatives of Benzotriazole and Piperidine

Stability of Benzotriazole Derivatives with Free Cu, Zn, Co and Metal-Containing Enzymes: Binding and Interaction of Methylbenzotriazoles with Superoxide Dismutase and Vitamin B12

Benzotriazole derivatives form very strong bonds with transition metals, and are the most widely used type of industrial corrosion inhibitor. Some benzotriazole derivatives have been implicated as hormone regulators which also carry the ability to induce uncoupling responses or otherwise inhibit respiration processes in some microorganisms. However, the mechanisms associated with benzotriazole toxicity and inhibition are unknown. Using Differential Pulse Polarography, the stability constants of commercially significant corrosion inhibitors, 4-and 5-methylbenzotriazole, coordinated with free Cu (II) and Co (III), were determined to be 1015 and 108, respectively. Polarographic analyses were extended to confirm that methylbenzotriazole also binds the copper center(s) in the ubiquitous enzyme superoxide dismutase, and the Corrin site in the coenzyme cobalamin (vitamin B12). These results suggest that the metal-chelating ability of this unique class of compounds may confer inhibition to certain enzyme systems.

Effects of Substitutions on the Biodegradation Potential of Benzotriazole Derivatives

Fourteen benzotriazole derivatives were subjected to microcosm tests to study the influence of substitutions on their biodegradation potential. Methylated, nitrated, carboxylated, and propionated bezotriazoles, a heterocyclic triazole, as well as methylated benzimidazoles, were introduced to activated sludge and soil enrichment cultures as the only carbon source. Some of the enrichment cultures were derived from airport soils that had been previously contaminated with aircraft deicing fluids and subsequently enriched with the commercially significant corrosion inhibitor methylbenzotriazole. The 5-methylbenzotriazole and only the carboxylated derivatives were degraded by soil or activated sludge biomass regardless of acclimation conditions. Radiotracer studies of [U-14C] 5-methylbenzotriazole, and [U-14C] 5-carboxybenzotriazole confirmed that relatively high concentrations (25mg L-1) of these derivatives can be completely mineralized in relatively short time frames by microbial consortia regardless of prior exposure. Observations suggested that the growth yield on these compounds is likely low. Biodegradation patterns suggested that carboxylated benzotriazole derivatives are more readily biodegradable than their more popular methylated counterparts.

Microwave-Assisted Synthesis and Biological Evaluation of Some Coumarin Hydrazides

In this work, 15 different coumarin hydrazides were successfully synthesized and screened for their antioxidant and antilipase activities. To do this, firstly, salicylaldehyde derivatives and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's Acid) were reacted in ethanol in the presence of catalytic amount of pyridine to obtain coumarin-3-carboxylic acid derivatives (1a-e). Then, these compounds were treated with benzotriazole in dichloromethane by using thionyl chloride to synthesized benzotriazole derivatives (2a-e). Then, compounds 2a-e were reacted with three commercial hydrazides (nicotinic hydrazide, benzhydrazide and phenylacetichydrazide) in ethanol by using microwave irradiation and conventional heating procedures to obtain final products (3-5a-e). Finally, these compounds were tested for their anti-oxidant and anti-pancreatic lipase activities. The structure of newly synthesized compounds was identified by 1H NMR, 13C NMR and elemental analysis data.

Molecular modeling for the investigation of UV absorbers for sunscreens: Triazine and benzotriazole derivatives

Investigations on the photoprotection mechanisms of molecular sunscreens is critical to developing more efficacious sunscreen products. Molecular modeling has proved to be very helpful in understanding intrinsic properties of molecules that protect our skin from the harmful rays of the sun and gathering useful features to developing improved sunscreens. Herein the investigation focuses on the stereoelectronic properties related to photoprotection mechanisms of triazine and benzotriazole derivatives, important compound classes based on their physical-chemical properties, such as resonance and ultraviolet (UV) broad spectrum absorption (UVA and UVB). The method proved to be a valuable tool to reproduce the experimental UV absorption of a set of triazine and benzotriazole derivatives with compromise between the accuracy and the computational speed. All calculations were carried out considering only the isolated UV filter (in vacuum) and have provided a qualitative prediction and interpretation of absorption properties. The lowest band gap energy (Ebg), highest chemical potential (μ) and lowest chemical hardness (η) values were observed to the orthohydroxy substituted derivatives that are able to undergo excited-state proton transfer (ESPT), supporting the UVA absorption and resulting in excellent photostability.

Environmental occurrence and distribution of organic UV stabilizers and UV filters in the sediment of Chinese Bohai and Yellow Seas.

Organic UV stabilizers and UV filters are applied to industrial materials and cosmetics worldwide. In plastics they prevent photo-induced degradation, while in cosmetics they protect human skin against harmful effects of UV radiation. This study reports on the occurrence and distribution of organic UV stabilizers and UV filters in the surface sediment of the Chinese Bohai and Yellow Seas for the first time. In total, 16 out of 21 analyzed substances were positively detected. Concentrations ranged from sub-ng/g dw to low ng/g dw. The highest concentration of 25 ng/g dw was found for octocrylene (OC) in the Laizhou Bay. In the study area, characteristic composition profiles could be identified. In Korea Bay, the dominating substances were OC and ethylhexyl salicylate (EHS). All other analytes were below their method quantification limit (MQL). Around the Shandong Peninsula, highest concentrations of benzotriazole derivatives were observed in this study with octrizole (UV-329) as the predominant compound, reaching concentrations of 6.09 ng/g dw. The distribution pattern of UV-329 and bumetrizole (UV-326) were related (Pearson correlation coefficient r > 0.98, p « 0.01 around the Shandong Peninsula), indicating an identical input pathway and similar environmental behavior.

Quantum Chemical Investigation of the Relationship Between Molecular Structure and Corrosion Inhibition Efficiency of Benzotriazole and its Alkyl-Derivatives on Iron

In this study, we have investigated possible role as iron corrosion inhibitor of four benzotriazole derivatives, BTA, BTA-C1, BTA-C4, BTA-C6, using DFT calculations at B3LYP/6-311G** level of theory. For this purpose, we have determined some structural and electronic parameters such as HOMO and LUMO orbital energies, energy gap, electron affinity, ionization potential, hardness, softness, absolute electronegativity, chemical potential, electrophilicity index, fractions of electrons transferred and back donation, logP, molecular surface area, polar surface area, molecular volume, molar refractivity and have compared with experimental literature results. We have also computed and discussed the interaction energy of the inhibitors with iron surface. The calculated parameters are closely related to the inhibition efficiencies, and have compared with experimental literature values using linear regression analysis to determine the most effective parameters on inhibition efficiency.

Determination of benzotriazoles and benzothiazoles in human urine by UHPLC-TQMS.

Benzotriazole (BTR) and benzothiazole (BTH) derivatives are extensively applied in industrial processes and consumer products, and are thus frequently detected in the environmental matrices. Due to their potential estrogenic effects reported in animal studies, the assessment of human exposure to BTRs and BTHs is important. In this study, a method was developed and validated to determine six BTRs and five BTHs in human urine by using ultra-high performance liquid chromatography coupled with a triple quadrupole mass spectrometry (UHPLC-TQMS) in positive electrospray ionization mode. After de-conjugation by β-glucuronidase, urine samples were liquid-liquid extracted for the measurement of total concentrations of BTRs and BTHs. The linearity, detection limit, precision, recovery, accuracy and matrix effect were evaluated. The limits of detection were less than 0.5ng/mL. The validated method demonstrated good precision (RSD%<15%), linearity (R2>0.99), recovery (>80%) and accuracy (80-100%). The method was successfully applied for the analysis of 22 human urine samples. Four out of eleven targeted compounds were detected in more than half of participants at ng/mL levels.

Penta and hexacoordinated aluminum(III) compounds containing benzotriazole and benzimidazole derivatives as ligands

Abstract New aluminum(III) pentacoordinated compounds were obtained from reactions of 2-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol (1) and 2-(1H-benzimidazol-2-yl)phenol (2) with two equivalents of Al(CH3)3 (3 and 4 respectively) or Al(CH3)2Cl (5 and 6). Ligands are bidentate, the aluminum is the center of a spiranic structure bound to two fused and planar tetracyclic systems. Solution of compound 6 in DMSO afforded a new ionic compound (7), which has two bidentate ligands and two DMSO molecules bound to a cationic aluminum with chloride as counterion. Compounds were characterized by 1H, 13C and 27Al NMR, mass spectrometry, elemental analysis and infrared spectroscopy. Crystals of compounds 3, 4 and 7 were submitted to X-ray diffraction analysis. Intra and intermolecular weak interactions were analyzed using the Quantum Theory of Atoms in Molecules (QTAIM) and the noncovalent interaction plots (NCI).

Pharmaceuticals and other anthropogenic chemicals in atmospheric particulates and precipitation

Air and precipitation samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC–MS) for pharmaceuticals, personal care products, and other commercial chemicals within the St. Paul/Minneapolis metropolitan area of Minnesota, U.S. Of the 126 chemicals analyzed, 17 were detected at least once. Bisphenol A, N,N-diethyl-meta-toluamide (DEET), and cocaine were the most frequently detected; their maximum concentrations in snow were 3.80, 9.49, and 0.171ng/L and in air were 0.137, 0.370, and 0.033ng/m3, respectively. DEET and cocaine were present in samples of rain up to 14.5 and 0.806ng/L, respectively. Four antibiotics - ofloxacin, ciprofloxacin, enrofloxacin, and sulfamethoxazole - were detected at concentrations up to 10.3ng/L in precipitation, while ofloxacin was the sole antibiotic detected in air at 0.013ng/m3. The X-ray contrast agent iopamidol and the non-steroidal anti-inflammatory drug naproxen were detected in snow up to 228ng/L and 3.74ng/L, respectively, while caffeine was detected only in air at 0.069 and 0.111ng/m3. Benzothiazole was present in rain up to 70ng/L, while derivatives of benzotriazole – 4-methylbenzotriazole, 5-methylbenzotriazole, and 5-chlorobenzotriazole - were detected at concentrations up to 1.5ng/L in rain and 3.4ng/L in snow. Nonylphenol and nonylphenol monoethoxylate were detected once in air at 0.165 and 0.032ng/m3, respectively. Although the sources of these chemicals to atmosphere are not known, fugacity analysis suggests that wastewater may be a source of nonylphenol, nonylphenol monoethoxylate, DEET, and caffeine to atmosphere. The land-spreading of biosolids is known to generate PM10 that could also account for the presence of these contaminants in air. Micro-pollutant detections in air and precipitation are similar to the profile of contaminants reported previously for surface water. This proof of concept study suggests that atmospheric transport of these chemicals may partially explain the ubiquity of these contaminants in the aquatic environment.

Thieno[3,2-b]pyrrolo-Fused Pentacyclic Benzotriazole-Based Acceptor for Efficient Organic Photovoltaics

A novel nonfullerene small molecular acceptor (BZIC) based on a ladder-type thieno[3,2-b]pyrrolo-fused pentacyclic benzotriazole core (dithieno[3,2-b]pyrrolobenzotriazole, BZTP) and end-capped with 1,1-dicyanomethylene-3-indanone (INCN) has been first reported in this work. Through introducing multifused benzotriazole and INCN, BZIC could maintain a high-lying lowest unoccupied molecular orbital (LUMO) energy level of -3.88 eV. Moreover, BZIC shows a low optical bandgap of 1.45 eV with broad and efficient absorption band from 600 to 850 nm due to increased π-π interactions by the covalently locking thiophene and benzotriazole units. A power conversion efficiency of 6.30% is delivered using BZIC as nonfullerene acceptor and our recently synthesized hexafluoroquinoxaline-based polymer HFQx-T as donor. This is the first time to synthesize mutifused benzotriazole-based molecules as nonfullerene electron acceptor up to date. The preliminary results demonstrate that the mutifused benzotriazole derivatives hold great potential for efficient photovoltaics.

Effect of the topology of benzotriazole derivatives on their chromatographic retention under RP-HPLC conditions

Sixth order connectivity indices are calculated for 29 benzotriazole derivatives. Correlations between the connectivity indices, physicochemical characteristics, and retention factors of the mentioned compounds are obtained for reversed-phase high-performance liquid chromatography conditions. Based on the correlations obtained, a predictive calculation of the retention factors of some benzotriazole derivatives is performed.

A novel “turn-on” fluorescence probe based on azoaniline-arylimidazole dyad for the detection of Cu2+

A novel fluorescence probe TPI-AD bearing azoaniline and arylimidazole moieties is conveniently synthesized for the detection of Cu2+. A “naked-eye” visible color change from colorless to lake-blue together with a 220-fold fluorescence enhancement can be achieved by Cu2+-catalyzed oxidative cyclization, which transforms the non-emissive TPI-AD into strongly fluorescence benzotriazole derivative (TPI-BTA). The TPI-AD probe can be applied for quantitative detection of Cu2+ with good linear relationship between its fluorescence intensity and Cu2+ concentration. Moreover, TPI-AD shows high selectivity over other common metal ions as well as excellent sensitivity with a detection limit of 14.4 nM. In addition, the fluorescence imaging of living cells MCF-7 reveals the potential application of TPI-AD in biological system.

Tunable emission in aggregated T-Shaped 2H-Benzo[d][1,2,3]triazoles with waveguide behaviour

Symmetrical Donor-Acceptor-Donor (D-A-D) 2H-benzo[d][1,2,3]triazole derivatives have been designed by DFT calculations and prepared by a multistep synthetic protocol. The design strategy involved the identification of a suitable acceptor benzotriazole core and modification of the steric volume and donor strength of the branches in order to modulate the Intramolecular Charge Transfer (ICT) process and, consequently, the band gap. Self-assembly of the reported triazoles afforded organized supramolecular structures, the morphologies of which were visualized by SEM imaging. The outcomes demonstrated the effect that the donor moiety has on the emission properties and the morphologies of the aggregates. The aggregates that had a crystal-like structure, with smooth surfaces and flat end facets, exhibited optical waveguide behaviour with tunable colour emission. Depending on the initial design, the different emission wavelengths are related to the band gap of the benzotriazole derivatives.

Synthesis, in vitro antiproliferative activity and kinase profile of new benzimidazole and benzotriazole derivatives

Protein kinase 2 (CK2), a member of the serine/threonine kinase family, has been established as a promising target in anticancer therapy. New derivatives of known CK2 inhibitors 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) bearing azide or substituted triazole groups were synthesized. Their influence on the activity of human recombinant CK2α and cytotoxicity against normal and cancer cell lines were evaluated. TBBi derivatives with triazole substituted with carboxyl substituent (7 and 10) exhibited the most potent inhibitory activity against CK2 with Ki value in the range of 1.96–0.91μM, respectively. New TBBi derivatives 2, 3, 5 and 9 have demonstrated the EC50, in the range of 12–25μM and 13–29μM respectively towards CCRF-CEM and MCF-7 cells. Derivatives TBBi decreased viability of cancer cells more efficiently than BALB cells and the biggest differences were observed for the azide substituted compounds 3 and 5. The effect of the most active compounds on the activity of eight off-target kinases was evaluated. Inhibitory efficiency of CK2-mediated p65 phosphorylation was demonstrated for the TBBi and compound 12.

N-Acyl Benzotriazole Derivatives for the Synthesis of Dipeptides and Tripeptides and Peptide Biotinylation by Mechanochemistry

An eco-friendly methodology for preparing Fmoc-, Z-, and Boc-N-protected dipeptides and tripeptides is described, from the corresponding N-protected-α-aminoacyl benzotriazoles and α-amino acid derivatives, with different C-terminal functionalities such as esters or amides, using vibrational ball-mill (VBM). The reactivity of a β-amino ester was also investigated. In some cases, the coupling was achieved by liquid-assisted grinding (LAG). α,α- and one α,β-dipeptide were obtained in good to excellent yields mainly by precipitation in water, resulting in an improved environmental impact compared to classical peptide synthesis in solution, as shown by green metric calculations. The method was extended to the biotinylation, via an aminohexanoyl spacer, of the pentapeptide RGDfV, which contains the well-known integrins recognition site arginine–glycine–aspartic acid (RGD) motif.

The discovery of new scaffold of plant activators: From salicylic acid to benzotriazole

Started from salicylic acid (SA) and related commercialized plant activators, based on molecular three-dimensional shape and pharmacophore similarity comparison (SHAFTS), a new lead compound benzotriazole was predicted and a series of benzotriazole derivatives were designed and synthesized. The bioassay showed that benzotriazole had high activity against a broad spectrum of diseases including fungi and oomycetes in vivo, but no activity in vitro. And the introduction of proper groups at the 1'-position and 5'-position was beneficial to the activity. So, they had the potential to be exploited as novel plant activators.

Benzotriazoles Reactivate Latent HIV-1 through Inactivation of STAT5 SUMOylation

SUMMARYThe presence of latent HIV-1 in infected individuals represents a major barrier preventingviral eradication. For that reason, reactivation of latent viruses in the presence of antiretroviral regimens has been proposed as a therapeutic strategy to achieve remission. We screened for small molecules and identified several benzotriazole derivatives with the ability to reactivate latent HIV-1. In the presence of IL-2, benzotriazoles reactivated and reduced the latent reservoir in primary cells, and, remarkably, viral reactivation was achieved without inducing cell proliferation, T cell activation, or cytokine release. Mechanistic studies showed that benzotriazoles block SUMOylation of phosphorylated STAT5, increasing STAT5’s activity and occupancy of the HIV-1 LTR. Our results identify benzotriazoles as latency reversing agents and STAT5 signaling and SUMOylation as targets for HIV-1 eradication strategies. These compounds represent a different direction in the search for “shock and kill” therapies.

Synthesis and Performance of New Benzotriazole Derivatives with Long Alkyl Chain as Corrosion Inhibitors

Synthesis and Performance of New Benzotriazole Derivatives with Long Alkyl Chain as Corrosion Inhibitors

Synthesis and in vitro antikinetoplastid activity of polyamine–hydroxybenzotriazole conjugates

Thirteen new polyamine derivatives coupled to hydroxybenzotriazole have been synthesized and evaluated for their in vitro antikinetoplastid activity. Trypanosoma Trypanothione reductase (TryR) was envisioned as a potential target. Among all tested molecules, only one compound, a N3-spermidine–benzotriazole derivative, displayed relevant inhibitory activity on this enzyme but was not active on parasites. The corresponding Boc-protected spermidine–benzotriazole was however trypanocidal against Trypanosoma brucei gambiense with an IC50 value of 1μM and was completely devoid of cytotoxicity. On the intramacrophage amastigotes of Leishmania donovani, a N2-spermidine conjugate of this series, exhibited an interesting IC50 value of 3μM associated with both low cytotoxicity against axenic Leishmania donovani. These new compounds are promising leads for the development of antikinetoplastid agents and their targets have to be deciphered.