Series Of Amines Research Articles

High Antimicrobial Effectiveness with Low Hemolytic and Cytotoxic Activity for PEG/Quaternary Copolyoxetanes

The alkyl chain length of quaternary ammonium/PEG copolyoxetanes has been varied to discern effects on solution antimicrobial efficacy, hemolytic activity and cytotoxicity. Monomers 3-((4-bromobutoxy)methyl)-3-methyloxetane (BBOx) and 3-((2-(2-methoxyethoxy)ethoxy)methyl)-3-methyloxetane (ME2Ox) were used to prepare precursor P[(BBOx)(ME2Ox)-50:50–4 kDa] copolyoxetane via cationic ring opening polymerization. The 1:1 copolymer composition and Mn (4 kDa) were confirmed by 1H NMR spectroscopy. After C–Br substitution by a series of tertiary amines, ionic liquid Cx-50 copolyoxetanes were obtained, where 50 is the mole percent of quaternary repeat units and “x” is quaternary alkyl chain length (2, 6, 8, 10, 12, 14, or 16 carbons). Modulated differential scanning calorimetry (MDSC) studies showed Tgs between −40 and −60 °C and melting endotherms for C14–50 and C16–50. Minimum inhibitory concentrations (MIC) were determined for Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. A systematic dependence of MIC on alkyl chain length was found. The most effective antimicrobials were in the C6–50 to C12–50 range. C8–50 had better overall performance with MICs of 4 μg/mL, E. coli; 2 μg/mL, S. aureus; and 24 μg/mL, P. aeruginosa. At 5 × MIC, C8–50 effected >99% kill in 1 h against S. aureus, E. coli, and P. aeruginosa challenges of 108 cfu/mL; log reductions (1 h) were 7, 3, and 5, respectively. To provide additional insight into polycation interactions with bacterial membranes, a geometric model based on the dimensions of E. coli is described that provides an estimate of the maximum number of polycations that can chemisorb. Chain dimensions were estimated for polycation C8–50 with a molecular weight of 5 kDa. Considering the approximations for polycation chemisorption (PCC), it is surprising that a calculation based on geometric considerations gives a C8–50 concentration within a factor of 2 of the MIC, 4.0 (±1.2) μg/mL for E. coli. Cx-50 copolyoxetane cytotoxicity was low for human red blood cells, human dermal fibroblasts (HDF), and human foreskin fibroblasts (HFF). Selectivities for bacterial kill over cell lysis were among the highest ever reported for polycations indicating good prospects for biocompatibility.

Comparison of Aminolysis of 2-Pyridyl and 4-Pyridyl X-Substituted Benzoates in Acetonitrile: Evidence for a Concerted Mechanism Involving a Cyclic Transition State

A kinetic study on reactions of 2-pyridyl X-substituted benzoates (6a-i) with a series of cyclic secondary amines in MeCN is reported. The Hammett plot for the reaction of 6a-i with piperidine consists of two intersecting straight lines while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρX = 1.28 and r = 0.63, indicating that the nonlinear Hammett plot is not caused by a change in the rate-determining step but rather by resonance stabilization of substrates possessing an electron-donating group (EDG) in the benzoyl moiety. The Brønsted-type plots are linear with βnuc = 0.59 ± 0.02, which is typical of reactions reported to proceed through a concerted mechanism. A cyclic transition state (TS), which forces the reaction to proceed through a concerted mechanism, is proposed. The deuterium kinetic isotope effect of 1.3 ± 0.1 is consistent with the proposed mechanism. Analysis of activation parameters reveals that ΔH(‡) increases linearly as the substituent X changes from an electron-withdrawing group (EWG) to an EDG, while TΔS(‡) remains nearly constant with a large negative value. The constant TΔS(‡) value further supports the proposal that the reaction proceeds through a concerted mechanism with a cyclic TS.

Well Plate Circular Dichroism Reader for the Rapid Determination of Enantiomeric Excess.

Circular dichroism (CD) spectropolarimeters typically employ one photoelastic modulator. However, spectropolarimeters employing two or even four modulators are more versatile and can be used to subvert common measurement errors arising from imperfectly isotropic samples or sample holders. Small linear anisotropies that can cause large errors in CD measurement can be associated with multi-well sample holders. Thus, high-throughput CD analyses in multi-well plates have not yet been demonstrated. One such application is the determination of enantiomeric excess of a library of reaction products. Herein, a spectropolarimeter employing four photoelastic modulators and a translation stage was used to determine the enantiomeric excess of a family of chiral amine complexes much more rapidly than could be achieved with a robotic fluid injection system. These experiments are proof of concept for high-throughput CD analysis. In practice, commercially available glass bottomed well plates are sufficiently strain free such that a simple instrument with just one photoelastic modulator and a vertical optical train should be able to deliver the CD without special considerations given herein. On the other hand, polystyrene well plates cannot be used in this way.

Structure–function study of tertiary amines as switchable polarity solvents

A series of tertiary amines have been screened for their function as switchable polarity solvents (SPS). The relative ratios of tertiary amine and carbonate species as well as maximum possible concentration were determined. A new form of SPS with an amine : carbonate ratio significantly greater than unity has been identified. The N,N-dimethyl-n-alkylamine structure has been identified as important to the function of an SPS.

Selective synthesis of secondary amines from nitriles using Pt nanowires as a catalyst

A new one-pot method has been developed for the selective synthesis of secondary amines via reductive amination of the corresponding nitriles using Pt nanowires as a catalyst. This method allows for the synthesis of both unsymmetrical and symmetrical secondary amines in excellent yields (up to 95%) in the presence or absence of additional amines, respectively. Furthermore, the reaction proceeds under mild conditions and is environmentally benign.

Nucleophilic displacement of ammonia from ammonia borane for the preparation of alkylamine-, pyridine- and phosphine-boranes

A near quantitative and safe preparation of a series of aliphatic amine- and phosphine-boranes from ammonia borane (AB) in refluxing THF has been achieved by exploiting the volatility of ammonia. A one-pot preparation of lithium aminoborohydrides from AB has also been described.

Synthesis of new pyrazole and antibacterial pyrazolopyrimidine derivatives

3-Substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines 2a--c were synthesized by treating 5-aminopyrazole-4-carbonitriles 1a--c with formamide. The reactivity of compounds 1a--c towards some cyclic anhydrides was studied. The condensation of 5-aminopyrazole-4-carbonitrile 1b with triethylorthoformate gives imidate 7b, which reacts with a series of primary amines and leads to pyrazolo[3,4-d]pyrimidine-4-amines 9 and 10. The reaction of imidate 7b with ammonia and hydroxylamine afforded pyrazolopyrimidine 2b and pyrazolo[3,4-d]pyrimidin-5-(4H)-ol 11, respectively. The synthesized compounds were completely characterized by 1H NMR, 13C NMR, IR, and HRMS. The antibacterial activity of some new synthesized compounds was evaluated and appeared to be significant.

Hull cell tests for evaluating the effects of polyethylene amines as brighteners in the electrodeposition of aluminum from dimethylsulfone-AlCl3 baths

Hull cell tests were carried out to examine a series of polyethylene amines to evaluate their abilities as brighteners in the electrodeposition of aluminum from a dimethylsulfone (DMSO2)-AlCl3 bath. The tests demonstrated the current density ranges that yielded bright, semi-bright, dull, burnt, and streaked Al deposits from the baths containing each polyethylene amine at a variety of concentrations. Among the amines examined in this study, triethylenetetramine (TETA) was found to be the most effective brightener, providing a bright Al deposit with the highest specular reflectance over a wide range of current densities. No correlation was found between the preferential crystal orientation of the Al and the brightness of the deposit, which along with the acquired scanning electron microscopy images, indicated that surface morphology was primarily responsible for the differences in brightness.

Kinetic Study on Nucleophilic Displacement Reactions of Y-Substituted-Phenyl 2-Methylbenzoates with Cyclic Secondary Amines in Acetonitrile: Effects of Modification of 2-MeO in Benzoyl Moiety by 2-Me on Reactivity and Reaction Mechanism

The second-order rate constants () have been measured spectrophotometrically for nucleophilic substitution reactions of Y-substituted-phenyl 2-methylbenzoates (6a-e) with a series of cyclic secondary amines in MeCN at . Comparison of the values for the reactions of 4-nitrophenyl 2-methylbenzoate (6d) with those reported previously for the corresponding reactions of 4-nitrophenyl 2-methoxybenzoate (5) reveals that 6d is significantly less reactive than 5, indicating that modification of 2-MeO in the benzoyl moiety of 5 by 2-Me (i.e., ) causes a significant decrease in reactivity. This supports our previous report that aminolysis of 5 proceeds through a six-membered cyclic intermediate, which is highly stabilized through intramolecular H-bonding interactions. The Brnsted-type plot for the reactions of 6d with a series of cyclic secondary amines is linear with , which appears to be a lower limit of for a stepwise mechanism with breakdown of an intermediate () being rate-determining step (RDS). The Brnsted-type plot for the reactions of 6a-e with piperidine is curved, i.e., the slope of Brnsted-type plot () decreases from -1.05 to -0.41 as the leaving-group basicity decreases. The nonlinear Brnsted-type plot has been taken as evidence for a stepwise mechanism with a change in RDS (e.g., from the step to the process as the leaving-group basicity decreases). Dissection of into the microscopic rate constants associated with the reactions of 6a-e with piperidine (e.g., and ratio) also supports the proposed mechanism.

Vapor-Phase Molecular Doping of Graphene for High-Performance Transparent Electrodes

Doping is an essential process to engineer the conductivity and work-function of graphene for higher performance optoelectronic devices, which includes substitutional atomic doping by reactive gases, electrical/electrochemical doping by gate bias, and chemical doping by acids or reducing/oxidizing agents. Among these, the chemical doping has been widely used due to its simple process and high doping strength. However, it also has an instability problem in that the molecular dopants tend to gradually evaporate from the surface of graphene, leading to substantial decrease in doping effect with time. In particular, the instability problem is more serious for n-doped graphene because of undesirable reaction between dopants and oxygen or water in air. Here we report a simple method to tune the electrical properties of CVD graphene through n-doping by vaporized molecules at 70 °C, where the dopants in vapor phase are mildly adsorbed on graphene surface without direct contact with solution. To investigate the dependence on functional groups and molecular weights, we selected a series of ethylene amines as a model system, including ethylene diamine (EDA), diethylene triamine (DETA), and triethylene tetramine (TETA) with increasing number of amine groups showing different vapor pressures. We confirmed that the vapor-phase doping provides not only very high carrier concentration but also good long-term stability in air, which is particularly important for practical applications.

Discovery of Tertiary Amine and Indole Derivatives as Potent RORγt Inverse Agonists.

A novel series of tertiary amines as retinoid-related orphan receptor gamma-t (RORγt) inverse agonists was discovered through agonist/inverse agonist conversion. The level of RORγt inhibition can be enhanced by modulating the conformational disruption of H12 in RORγt LBD. Linker exploration and rational design led to the discovery of more potent indole-based RORγt inverse agonists.

An Efficient Method for the Protection of Aromatic Amines with Benzostabase and Its Utility in Anionic Aromatic Transformations

Herein we describe an efficient and generally applicable method of protecting a diverse series of aromatic amines with the ‘benzostabase’ group. We also demonstrate its efficient use in aromatic anionic chemistry including its utility in the anionic ortho Snieckus–Fries rearrangement.

ChemInform Abstract: Solvent‐ and Catalyst‐Free Direct Reductive Amination of Aldehydes and Ketones with Hantzsch Ester: Synthesis of Secondary and Tertiary Amines.

AbstractThe parallel synthesis of a series of secondary and tertiary amines is achieved by the direct reductive amination of aldehydes and ketones with a biomimetic and safe reducing agent under solvent‐ and catalyst‐free as well as metal‐ and acid‐free conditions.

A Facile and Efficient Synthesis of Diaryl Amines or Ethers under Microwave Irradiation at Presence of KF/Al2O3 without Solvent and Their Anti-Fungal Biological Activities against Six Phytopathogens

A series of diaryl amines, ethers and thioethers were synthesized under microwave irradiation efficiently at presence of KF/Al2O3 in 83%–96% yields without any solvent. The salient characters of this method lie in short reaction time, high yields, general applicability to substrates and simple workup procedure. At the same time, their antifungal biological activities against six phytopathogen were evaluated. Most of the compounds (3b, 3c, 3g–o) are more potent than thiophannate-methyl against to Magnaporthe oryzae. This implies that diaryl amine or ether moiety may be helpful in finding a fungicide against Magnaporthe oryzae.

Synthesis and evaluation of some variants of the Nefkens’ reagent

A series of N-substituted phthalimides have been prepared in an effort to explore synthetic variants of the Nefkens’ reagent. Three N-acylphthalimides [R=–CH3, –CH2CH3, and –C(CH3)3] were prepared and employed for the protection of a series of representative amines. In addition, an N-methanesulfonylphthalimide and N-(diethylphosphoryl)phthalimide were also prepared. It was determined that among the phthalimides that were prepared N-propanoylphthalimide was the most effective reagent for the protection reaction.

A Kinetic Study on Aminolysis of Benzyl 2-Pyridyl Thionocarbonate and t-Butyl 2-Pyridyl Thionocarbonate: Effects of Polarizability and Steric Hindrance on Reactivity and Reaction Mechanism

Received May 2, 2013, Accepted May 7, 2013 Second-order rate constants kN have been measured for reactions of benzyl 2-pyridyl thionocarbonate (4b) and t-butyl 2-pyridyl thionocarbonate (5b) with a series of cyclic secondary amines in MeCN at 25.0 ± 0.1 o C. The kN values for the reactions of 4b and 5b have been compared with those reported previously for the corresponding reactions of benzyl 2-pyridyl carbonate (4a) and t-butyl 2-pyridyl carbonate (5a) to investigate the effect of changing the electrophilic center from C=O to C=S on reactivity and reaction mechanism. The thiono compound 4b is more reactive than its oxygen analogue 4a. The Bronsted-type plots for the reactions of 4a and 4b are linear with βnuc = 0.57 and 0.37, respectively. The reactions of 4a were previously reported to proceed through a concerted mechanism, while those of 4b in this study have been concluded to proceed through a stepwise mechanism with formation of an intermediate being the rate-determining step on the basis of the βnuc value of 0.37. Enhanced polarizability upon changing the C=O in 4a by C=S has been suggested to be responsible for the reactivity order and the contrasting reaction mechanisms. In contrast, the reactivity of 5a and 5b is similar, but they are much less reactive than 4a and 4b. Furthermore, the reactions of 5a and 5b have been concluded to proceed through the same mechanism (i.e., a concerted mechanism) on the basis of linear Bronsted-type plots with βnuc = 0.45 or 0.47. It has been concluded that the strong steric hindrance exerted by the t-Bu in 5a and 5b causes a decrease in their reactivity and forces the reactions to proceed through a concerted mechanism.

Synthesis, in vitro evaluation and molecular modelling of naphthalimide analogue as anticancer agents

A series of amine substituted naphthalimide analogue were synthesized and evaluated for in vitro anti-tumour activities against 60 tumour cell lines at a single dose concentration of 10 μM. These new analogue showed potential anticancer activities against various cancer cell lines. Compound 5d exhibited significant growth inhibition and was evaluated as 60 cell panel at five dose concentration levels. Compound 5d proved to be fivefold more active than standard antitumour drug 5-fluorouracil (5-FU) with MG-MID GI50 and TGI values of 5.05 and 38.71 respectively. ct-DNA binding studies of most active compound 5d revealed strong interacting properties. Molecular docking studies in the active binding site provided complementary theoretical support for the experimental biological data acquired.

One-stage synthesis of adamantyl-containing α-aminonitriles

Reactions of 2-adamantan-2-one, acetone cyanohydrin, and amine lead to the formation of substituted 2-amino-2-cyanoadamantanes. The reaction is of a general character as has been proved by examples on a series of ketones and amines and it proceeds through the formation from the acetone cyanohydrin and amines of 2-amino-2-cyanopropane derivatives reacting further with the carbonyl compounds.

Role of the viral hemagglutinin in the anti-influenza virus activity of newly synthesized polycyclic amine compounds

We here report on the synthesis of new series of polycyclic amines initially designed as ring-rearranged analogs of amantadine and featuring pentacyclo, hexacyclo, and octacyclo rings. A secondary amine, 3-azahexacyclo[7.6.0.01,5.05,12.06,10.011,15]pentadeca-7,13-diene, 3, effectively inhibited A/M2 proton channel function, and, moreover, possessed dual activity against an A/H3N2 virus carrying a wild-type A/M2 proton channel, as well as an amantadine-resistant A/H1N1 virus. Among the polycyclic amines that did not inhibit influenza A/M2 proton channel function, several showed low-micromolar activity against tested A/H1N1 strains (in particular, the A/PR/8/34 strain), but not A/H3N2 influenza viruses. A/PR/8/34 mutants selected for resistance to these compounds possessed mutations in the viral hemagglutinin that markedly increased the hemolysis pH. Our data suggest that A/H1N1 viruses such as the A/PR/8/34 strain are particularly sensitive to a subtle increase in the endosomal pH, as caused by the polycyclic amine compounds.

Palladium catalysts supported on amine-functionalized glycidyl methacrylate gel type terpolymers. Synthesis, characteristics and study of catalytic activity in Suzuki–Miyaura reactions

A series of amine functionalized resins (1–7) with ethylenediamine (EDA), N,N-dimethylethylenediamine (DMEDA), N,N-diisopropylethylenediamine (DIPEDA), 2-methoxyethylamine (MEOEA), diethylenetriamine (DETA), tris(2-aminoethyl)amine (TAEA), triethylenetetramine (TETA) functionalities were prepared by chemical modification of the terpolymer of glycidyl methacrylate (20mol%), styrene (77mol%) and divinylbenzene (3mol%). The resins obtained in this way were used for preparation of two series of polymer supported palladium catalysts consisting of about 3.6wt% of Pd(II) ions (N/Pd>2) and maximal possible loadings of Pd(II) ions (8.0–15.9wt% Pd, N/Pd<2). The catalysts were characterized using FT-IR, DR UV–Vis, HR-SEM and ICP-OES methods. Catalytic studies of the cross-coupling reaction of bromobenzene and phenylboronic acid in a medium of the i-PrOH/H2O solvent system with KOH as a base were also performed. The effect of catalyst and KOH concentrations, the nature of amine units and aryl bromides and reaction temperature was studied. The most active catalyst could be used minimum five times to perform the coupling of bromobenzene and phenylboronic acid efficiently. However, the lowering of the catalyst activity was observed after each cycle.