Alkyl-substituted Derivatives Research Articles

Preparation of Dearomatized p-Coumaric Acid Derivatives as DNA Damage Response Inhibitors with Potent In Vitro Antitumor Effect.

Our research group previously identified graviquinone (1) as a promising antitumor metabolite that is formed in situ when the antioxidant methyl caffeate scavenges free radicals. Furthermore, it exerted a DNA damaging effect on cancer cells and a DNA protective effect on normal keratinocytes. To expand and explore chemical space around qraviquinone, in the current work we synthesized 9 new alkyl-substituted derivatives and tested their in vitro antitumor potential. All new compounds bypassed ABCB1-mediated multidrug resistance and showed highly different cell line specificity compared with 1. All compounds were more potent in MDA-MB-231 than on MCF-7 cells. The n-butyl-substituted derivatives 2 and 8 modulated the cell cycle and inhibited the ATR-mediated phosphorylation of checkpoint kinase-1 in MCF-7 cells. As a significant expansion of our previous findings, our results highlight the potential antitumor value of alkyl-substituted graviquinone derivatives.

Mono-Alkyl-Substituted Phosphinoboranes (HRP–BH2–NMe3) as Precursors for Poly(alkylphosphinoborane)s: Improved Synthesis and Comparative Study

A new synthetic pathway to various mono-alkyl-substituted phosphinoboranes HRP–BH2–NMe3 has been developed. The new synthetic route starting from alkyl halides and NaPH2 followed by metalation and salt metathesis is performed in a one-pot procedure and leads to higher yields and purity of the resulting phosphinoboranes, as compared to previously reported routes. Additionally, the scope of accessible compounds could be expanded from short-chained linear alkyl substituents to longer-chained linear alkyl substituents as well as secondary or functionalized alkyl substituents. The reported examples include primary alkyl-substituted phosphinoboranes RHP-BH2-NMe3 (R = n-butyl, n-pentyl, n-hexyl; 1a–c), the secondary alkyl-substituted derivatives iPrPH-BH2-NMe3 (2), and the functionalized alkyl-substituted 4-bromo-butyl-phosphinoborane (BrC4H8)PH-BH2-NMe3 (3). Compounds 1a, 1c, and 2 were additionally used for preliminary polymerization reactions via a thermal and a transition metal-catalyzed pathway, revealing the formation of high-molecular-weight polymers under certain conditions. Detailed investigations on the influence of temperature, concentration, substituents and reaction time on the respective polymerization reactions were performed.

Spatial and temporal trends of polycyclic aromatic hydrocarbons in sediment cores of Brunei Bay, East Malaysia

The spatial and temporal distribution of polycyclic aromatic hydrocarbons (PAHs) in three sediment cores from Brunei Bay, Southern South China Sea was investigated. The total concentrations of 16 priority PAHs (∑PAH16) and their alkyl-substituted derivatives ranged from 10.4 to 376 ng g−1 and 30.7 to 2263 ng g−1, respectively. PAH biomarker diagnostic ratios and principal component analysis (PCA) combined with absolute principal component score (APCS) and multiple linear regression (MLR) were performed to apportion the source contribution. The results revealed mixed inputs of fuel combustion residues and uncombusted petrogenic products. The downcore PAH profile revealed that the highest peaks could be related to past human activities using biofuel and coal during the industrialization/agriculture revolution period. The 1,7/(2,6+1,7)-dimethylphenanthrene ratio also highlighted wood combustion during forest fire outbreaks, which appeared to coincide with the past climate events.

Spectroscopic characterization and photochemistry of the Criegee intermediate CF3C(H)OO

Criegee intermediates (CIs), also known as carbonyl oxide, are reactive intermediates that play an important role in the atmospheric chemistry. Investigation on the structures and reactivity of CIs is of fundamental importance in understanding the underlying mechanism of their atmospheric reactions. In sharp contrast to the intensively studied parent molecule (CH2OO) and the alkyl-substituted derivatives, the knowledge about the fluorinated analogue CF3C(H)OO is scarce. By carefully heating the triplet carbene CF3CH in an O2-doped Ar-matrix to 35 K, the elusive carbonyl oxide CF3C(H)OO in syn- and anti-conformations has been generated and characterized with infrared (IR) and ultraviolet-visible (UV-vis) spectroscopy. The spectroscopic identification is supported by 18O-labeling experiments and quantum chemical calculations at the B3LYP/6-311++G(3df,3pd) and MP2/6-311++G(2d,2p) levels. Upon the long-wavelength irradiation (λ > 680 nm), both conformers of CF3C(H)OO decompose to give trifluoroacetaldehyde CF3C(H)O and simultaneously rearrange to the isomeric dioxirane, cyclic-CF3CH(OO), which undergoes isomerization to the lowest-energy carboxylic acid CF3C(O)OH upon UV-light excitation at 365 nm. The O2-oxidation of CF3CH via the intermediacy of CF3C(H)OO and cyclic-CF3CH(OO) might provide new insight into the mechanism for the degradation of hydro-chlorofluorocarbon CF3CHCl2 (HCFC-123) in the atmosphere.

High-Yield Production of Deoxygenated Monomers from Kraft Lignin over ZnO-Co/N-CNTs in Water

Catalytic conversion of technical lignin to value-added chemicals and fuels is important for realizing economically viable lignocellulosic biomass refineries. The choice of catalysts and solvents is critical for the effective conversion of the technical lignin to chemicals and fuels by the cleavage of the C–C bonds. In this study, catalytic depolymerization and hydrodeoxygenation of Kraft lignin (KL) were investigated over bimetallic ZnO and Co deposited on N-doped carbon nanotubes (ZnO-Co/N-CNTs) in an aqueous medium. The catalytic activity of ZnO-Co/N-CNTs was compared with those of various noble and non-noble metal-based catalysts. Almost complete KL conversion with a very low solid residue yield (5 wt %), a high bio-oil yield (52 wt %), a high degree of deoxygenation (DOD, 59.0%), and a high monomeric yield (12.1 wt %) was achieved over ZnO-Co/N-CNTs at 350 °C and 6 h reaction time. The monomers mainly consisted of cyclohexanone and its alkyl-substituted derivatives and alkylated phenols. At 400 °C, the monomeric yield and DOD increased to 24.4 wt %and 61.0%, respectively. In addition, the produced bio-oil exhibited high-calorific values of 34.3–37.0 MJ kg–¹ because of the high activity of ZnO-Co/N-CNTs for hydrodeoxygenation. ZnO-Co/N-CNTs outperformed most of the metal-supported catalysts including 5 wt % Pd, 5 wt % Ru, 5 wt % Pt, 66 wt % Ni, and CoMo on various supports of activated carbon and alumina. The use of water as the solvent resulted in much higher bio-oil and monomeric yields than those using methanol, isopropyl alcohol, and n-hexane (12–37 and 3.2–4.1 wt %, respectively). The high bio-oil and monomeric yields with a high DOD in water make ZnO-Co/N-CNTs highly attractive in the development of an environmentally friendly technical lignin conversion process.

Boosting Room Temperature Phosphorescence Performance by Alkyl Modification for Intravital Orthotopic Lung Tumor Imaging.

Pure organic persistent room temperature phosphorescence (RTP) materials have attracted wide attention owing to their great potential in various applications, particularly in bioimaging. However, it is still a challenge to manufacture organic RTP materials possessing quite high efficiency and long lifetime, owing to the high requirements for triplet excitons. In this study, a series of keto derivatives with efficient RTP in crystals are developed through the regulation of molecular aggregation states by simple alkyl groups, resulting in impressive luminescence performance with a longer lifetime and higher efficiency of up to 868ms and 51.59%, respectively. All the alkyl-substituted derivatives exhibit bright RTP intensities after heavy grinding with a pestle, indicating their robust RTP features, which are suitable for many fields. Encouraged by the excellent RTP performance of these luminogens in the crystalline state, successful orthotopic lung tumor imaging with a high signal-to-background ratio (SBR) of 65 is demonstrated in this study to provide the promise of pure organic RTP materials for disease diagnosis, which hold the advantages of low autofluorescence interference and high signal-to-background ratio.

Kinetic parameters of the concerted decomposition of alkyl-substituted cyclohexene derivatives

The kinetic and thermodynamic parameters of the concerted decomposition of cyclohexenes of various structures were calculated by two methods: the method of three intersecting parabolas and quantum chemical modeling (hybrid density functional theory B3LYP method and the 6–311++G** basic set). The activation energies, rate constants, and enthalpies for nine decomposition reactions were determined for the first time. The parameters of the decomposition of cyclohexenes calculated by two independent methods are in good agreement with each other.

α-Substituted Lactams and Acetamides: Ion Channel Modulators that Show Promise in Treating Drug-resistant Epilepsy.

The two main problems in the pharmacotherapy of epilepsy are resistance to currently available first-line medications (which occurs in about one third of patients) and the high incidence of side effects. To address these two challenges, extensive efforts are being undertaken to design new, structurally distinct antiepileptic drugs with a broad spectrum of anticonvulsant activity. Tests in animal models of epilepsy indicate that α-substituted lactams and acetamides show a broad spectrum of anticonvulsant activity (including very promising activity in drug-resistant models) as well as an excellent safety profile. Limited clinical results confirm these preclinical findings. In the first part of this review, pharmacology and toxicology of α-substituted lactams and acetamides and their putative protein targets in the brain have been discussed. This is followed by a discussion of structure-activity relationships among α-alkyl-, α-aryl-, and α-aryl-α-alkyl-substituted derivatives. The most promising structures seem to be those related to 3-ethyl-3-phenylpyrrolidin-2-one, 2-phenylbutyramide, and 2- sec-butylvaleramide. The information presented in this review is expected to facilitate rational drug design and development efforts for α-substituted lactams and acetamides.

Application of ionizing radiation in decomposition of perfluorooctane sulfonate (PFOS) in aqueous solutions

The radiolytic methods of PFOS decomposition in aqueous solutions investigated in this work for potential environmental applications are based on the use of gamma rays or a beam of accelerated electrons (EB) under different chemical conditions in irradiated solutions. The most active reagents in the employed conditions are hydrated electrons from water radiolysis. There are also OH and H radicals which take part in the occurring reactions. In the presence of formate and 2-propanol in irradiated solutions, the reductive radicals derived from them (CO2−, (CH2)2C-OH) are able to induce reductive decomposition of PFOS. In turn, in the presence of tert-butanol, the radicals derived from the alcohol and PFOS dimerize forming alkyl-substituted derivatives. The most favorable conditions for irradiation were achieved in neutral deaerated solutions and aerated solutions containing 10 mM 2-propanol. In γ-irradiation processes the pseudo-first order rate-constants of PFOS decomposition are 0.0197 min−1 (0.310 kGy−1), and 0.0060 min−1 (0.0947 kGy−1), respectively, under both conditions. Due to a big difference in the dose-rate between the two employed types of radiation (gamma and EB), the values of pseudo-first order rate constants of PFOS decomposition are different, namely 0.0197 min−1 (0.310 kGy−1) and 0.368 s−1 (0.0184 kGy−1), respectively, for γ and EB radiation used for decomposition of 0.1 mg L−1 PFOS in neutral, deaerated solution. The EB-irradiation processes for PFOS decomposition are much more efficient than any other AO/RPs reported so far and can be easily employed at a technological scale for very large volumes of treated solutions. The gamma irradiation-based PFOS decomposition requires smaller absorbed doses and it does not require any external energy input because of the use of the isotope source of radiation.

Qualitative characterization of three combustion-related standard reference materials for polycyclic aromatic sulfur heterocycles and their alkyl-substituted derivatives via normal-phase liquid chromatography and gas chromatography/mass spectrometry.

The research described here provides the most comprehensive qualitative characterization of three combustion-related standard reference materials (SRMs) for polycyclic aromatic sulfur heterocycles (PASHs) and some alkyl-substituted (alkyl-) derivatives to date: SRM 1597a (coal tar), SRM 1991 (coal tar/petroleum extract), and SRM 1975 (diesel particulate extract). An analytical approach based on gas chromatography/mass spectrometry (GC/MS) is presented for the determination of three-, four-, and five-ring PASH isomers and three- and four-ring alkyl-PASHs in the three SRM samples. The benefit of using a normal-phase liquid chromatography (NPLC) fractionation procedure prior to GC/MS analysis was demonstrated for multiple isomeric PASH groups. Using a semi-preparative aminopropyl (NH2) LC column, the three combustion-related samples were fractionated based on the number of aromatic carbon atoms. The NPLC-GC/MS method presented here allowed for the following identification breakdown: SRM 1597a - 35 PASHs and 59 alkyl-PASHs; SRM 1991-31 PASHs and 58 alkyl-PASHs; and SRM 1975-13 PASHs and 25 alkyl-PASHs. These identifications were based on NPLC retention data, the GC retention times of reference standards, and the predominant molecular ion peak in the mass spectrum. Prior to this study, only 11, 1, and 0 PASHs/alkyl-PASHs had been identified in SRM 1597a, SRM 1991, and SRM 1975, respectively. Graphical abstract NPLC-GC/MS analysis for the three- and four-ring parent PASH isomers in SRM 1597a.

Qualitative characterization of three combustion-related standard reference materials for polycyclic aromatic sulfur heterocycles and their alkyl-substituted derivatives via gas chromatography/mass spectrometry

Qualitative characterization of three combustion-related standard reference materials for polycyclic aromatic sulfur heterocycles and their alkyl-substituted derivatives via gas chromatography/mass spectrometry

Sulfur extraction from liquid fuels using trihexyl(tetradecyl)phosphonium tetrafluoroborate: as promising solvent.

Sulfur extraction from fuel is essential to be done for environmental and industrial point of view. Extractive desulfurization (EDS) is one of the most promising techniques in order to achieve legislative sulfur content requirements. Among numerous extractants and solvents, ionic liquids (ILs) are more capable due to their desirable green solvent properties. This work demonstrated that trihexyl(tetradecyl)phosphonium tetrafluoroborate ([THTDP]BF4) was synthesized, characterized, and employed as extraction solvent for extraction of dibenzothiophene (DBT), thiophene, benzothiophene, and other alkyl-substituted derivatives of sulfur from liquid fuel. Molecular confirmation and purity of synthesized ([THTDP]BF4) were analyzed with FTIR, Raman, NMR, EPR, UV, TG/DSC, and XRD analyses. Also, physical properties of ([THTDP]BF4) were carried out. The effects of extraction time, temperature, sulfur compounds, ultra-sonication, and ([THTDP]BF4) recycling/regeneration on DBT removal from liquid fuel were also examined. DBT removal in n-dodecane was 92.6% using EDS with mass ratio (1:1) in 30min at 30°C under the mild reaction conditions. ([THTDP]BF4) could be reused up to ten cycles for sulfur extraction and regenerated for few more cycles with good DBT removal ability. Also, the sulfur extraction from real fuels and multistage extraction performance were tested. The experimental data and results provided in this article discover the remarkable understandings of tetrafluoroborate-based phosphonium ionic liquids as promising solvent for EDS.

Novel multi-targeted agents for Alzheimer's disease: Synthesis, biological evaluation, and molecular modeling of novel 2-[4-(4-substitutedpiperazin-1-yl)phenyl]benzimidazoles

The present study describes the synthesis, pharmacological evaluation (BChE/AChE inhibition, Aβ antiaggregation, and neuroprotective effects), and molecular modeling studies of novel 2-[4-(4-substitutedpiperazin-1-yl)phenyl]benzimidazole derivatives. The alkyl-substituted derivatives exhibited selective inhibition on BChE with varying efficiency. Compounds 3b and 3d were found to be the most potent inhibitors of BChE with IC50 values of 5.18 and 5.22μM, respectively. The kinetic studies revealed that 3b is a partial non-competitive BChE inhibitor. Molecular modeling studies also showed that the alkyl-substituted derivatives were able to reach the catalytic anionic site of the BChE. The compounds with an inhibitory effect on BChE were subsequently screened for their Aβ antiaggregating and neuroprotective activities. Compounds 3a and 3b exerted a potential neuroprotective effect against H2O2 and Aβ-induced cytotoxicity in SH-SY5Y cells. Collectively, 3b was found as the most promising compound for the development of multi-target directed ligands against Alzheimer’s disease.

Aerobic degradation of adamantanes at highly acidic conditions

Biodegradation of alkyl-substituted adamantane derivatives (1-methyl, 1,3-dimethyl-, and 1,3,5-trimethyladamantane) by slow-growing bacteria Mycobacterium AGS10 was studied. The process was carried out under extremely acidic conditions (pH 2.5). Bacterial strain AGS10 was able to utilize these alicyclic hydrocarbons with a high degree of condensation and diamond-like structure, which are usually resistant to microbial transformation. Efficiency of alkyaldamantane biodegradation by the cells growing with these substrates as the sole carbon and energy sources was affected significantly by their aggregate state, which depended on molecular structure. Compared to the solid 1-methyladamantane, 1,3-dimethyladamantane, which is liquid under normal conditions, was a preferable substrate. Adamantanes in the gas condensate were generally more resistant to bacterial degradation than such markers as normal and isoprenoid alkanes. Moreover, biodegradation had no significant effect on relative distribution of the tested С11–С13 alkyladamantanes.

Coordination of cucurbit [6]uril and its alkyl-substituted derivatives with the lanthanum cation and the supramolecular assemblies formed with the aid of inorganic anions

We have investigated the interactions of the lanthanum cation (La3+) with cucurbit [6]uril (Q [6]) and its alkyl-substituted derivatives (SQ [6]s), including symmetrical tetramethylcucurbit [6]uril (TMeQ [6]), symmetrical dicyclohexanocucurbit [6]uril (1,4-DiCyHQ [6]), and percyclohexanocucurbit [6]uril (CyH6Q [6]), as well as the supramolecular assemblies formed with the aid of inorganic anions (NO3− and Cl−) as structure-directing agents. Single-crystal X-ray diffraction analysis has revealed that the interaction results in the formation of three kinds of coordination complexes. The main driving forces may be the ion-dipole interaction of inorganic anions and the electropositive outer surface of Q[n].

Amorphous Solid Simulation and Trial Fabrication of the Organic Field-Effect Transistor of Tetrathienonaphthalenes Prepared by Using Microflow Photochemical Reactions: A Theoretical Calculation-Inspired Investigation.

The p-type organic semiconductor (OSC) material tetrathieno[2,3-a:3',2'-c:2″,3″-f:3‴,2‴-h]naphthalene (2TTN) and its alkyl-substituted derivatives C(n)-2TTNs (n = 6, 8, and 10) have been developed based on the results of theoretical calculation-inspired investigation. A hole mobility for amorphous C(n)-2TTNs (10(-2)-10(-3) cm(2) V(-1) s(-1)) was accurately predicted by using a novel statistical method in which the geometric mean of the mobilities for many individual small molecular flocks in an amorphous solid was obtained by using molecular mechanical molecular dynamics simulations and quantum chemical calculations. The simulation also suggests that upon increasing the length of alkyl chains in C(n)-2TTNs the mobilities become smaller as a consequence of a decrease in transfer integral values. C(n)-2TTNs are synthesized in a microflow reactor through photoreactions of the corresponding precursors. C(n)-2TTNs are then utilized in the fabrication of organic field-effect transistors (OFETs). Although spin-coated thin films of C(n)-2TTNs are crystalline, the hole mobilities (10(-2)-10(-3) cm(2) V(-1) s(-1)) of trial OFETs decrease upon elongation of the alkyl chains. This finding parallels the results of theoretical simulation. The simulation method for amorphous solids developed in this effort should become a useful tool in studies aimed at designing new OSC materials.

Candida antarctica lipase B-catalyzed regioselective deacylation of dihydroxybenzenes acylated at both phenolic hydroxy groups

Candida antarctica lipase B proved to be highly active in the deacylation of substituted hydroquinones and resorcinols acylated at both phenolic hydroxy groups. The deacylation reactions were much faster than the corresponding direct acylations of these dihydroxybenzenes catalyzed by the same lipase. More importantly, they took place generally in a markedly regioselective manner: the acyloxy group remote from the substituent was preferentially cleaved. The main or exclusive products obtained were the regioisomers of those produced through the direct acylation of the dihydroxybenzenes. In the case of alkyl-substituted hydroquinone derivatives, the regioselectivity increased with an increase in the bulk of the substituent. In the case of 4-substituted diacylated resorcinols, the 3-O-monoacyl derivatives were obtained generally as the sole products. Quite interestingly, some secondary alcohols proved to act as better acyl acceptors than the corresponding primary alcohols in these enzymatic deacylations.

Sorption of americium(III) from multicomponent solutions with sorbents based on dibenzo-18-crown-6 and its derivatives

A sorption of metals from multicomponent nitric acid solutions that simulate process solutions resulting from reprocessing of spent nuclear fuel was studied. The sorbent used was a highly porous polymeric sorbent impregnated with crown ethers. Chemicals used in the work were dibenzo-18-crown-6 (DB18C6) and its alkyl-substituted derivatives: di-tert-butyldibenzo-18-crown-6 (DTBDB18C6) and diisooctyldibenzo-18-crown-6 (DIODB18C6). Sorption coefficients were determined for all elements. With the aim to study the possibility of isolation of 241Am from multicomponent solutions, separation factors for Am and ballast elements were determined. The possibility of application of sorbents impregnated with crown ethers for recovery of 241Am from multicomponent process solutions was shown.

Oxidative desulfurization of diesel fraction with hydrogen peroxide in the presence of catalysts based on transition metals

The oxidative desulfurization of a straight-run, nonhydrotreated diesel fraction (boiling range 178–342°C) containing benzothiophene, dibenzothiophene, their alkyl-substituted derivatives, and thioxanthene by the action of hydrogen peroxide in the presence of transition metal compounds (Na2MoO4, Na2WO4, NaVO3, WO3, tungstic acid, and heteropoly tungstate/molybdate H3PMo6W6O40) in a biphasic system followed by the extraction of the oxidation products with dimethylformamide has been studied. The oxidation of the hydrocarbon fraction in the presence of heteropoly tungstate/molybdate under biphasic conditions provides for the removal of up to 82% of total sulfur.

Sulfur K-edge X-ray absorption spectroscopy and time-dependent density functional theory of arsenic dithiocarbamates.

S K-edge X-ray absorption spectroscopy (XAS) and time-dependent density functional theory (TDDFT) calculations were performed on a series of As[S2CNR2]3 complexes, where R2 = Et2, (CH2)5 and Ph2, to determine how dithiocarbamate substituents attached to N affect As[S2CNR2]3 electronic structure. Complimentary [PPh4][S2CNR2] salts were also studied to compare dithiocarbamate bonding in the absence of As. The XAS results indicate that changing the orientation of the alkyl substituents from trans to cis (R2 = Et2vs. (CH2)5) yields subtle variations whereas differences associated with a change from alkyl to aryl are much more pronounced. For example, despite the differences in As 4p mixing, the first features in the S K-edge XAS spectra of [PPh4][S2CNPh2] and As[S2CNPh2]3 were both shifted by 0.3 eV compared to their alkyl-substituted derivatives. DFT calculations revealed that the unique shift observed for [PPh4][S2CNPh2] is due to phenyl-induced splitting of the π* orbitals delocalized over N, C and S. A similar phenomenon accounts for the shift observed for As[S2CNPh2]3, but the presence of two unique S environments (As-S and As···S) prevented reliable analysis of As-S covalency from the XAS data. In the absence of experimental values, DFT calculations revealed a decrease in As-S orbital mixing in As[S2CNPh2]3 that stems from a redistribution of electron density to S atoms participating in weaker As···S interactions. Simulated spectra obtained from TDDFT calculations reproduce the experimental differences in the S K-edge XAS data, which suggests that the theory is accurately modeling the experimental differences in As-S orbital mixing. The results highlight how S K-edge XAS and DFT can be used cooperatively to understand the electronic structure of low symmetry coordination complexes containing S atoms in different chemical environments.