Development of Bicyclic Compounds Containing a Tertiary Amine Moiety as T Cell Activators.

Thermoresponsive polymers exhibiting unique reversible phase transition properties in aqueous solution in response to temperature stimuli have been extensively investigated. In the past two decades, thermoresponsive polymers based on tertiary amine moieties have achieved considerable progress and become an important family of thermoresponsive polymers, including tertiary amine functionalized poly((meth)acrylamide)s, poly((meth)acrylate)s, poly(styrene)s, poly(vinyl alcohol)s, and poly(ethylene oxide)s, which exhibit lower critical solution temperature and/or upper critical solution temperature in water or aliphatic alcohols. Their phase transition behavior can be modulated by the solution pH and CO2 due to the protonation of tertiary amine moieties in acidic condition and deprotonation in alkaline condition and the charged ammonium bicarbonate formed by the tertiary amine moieties and CO2 . The aim of this review is to summarize the recent progress in the thermoresponsive polymers based on tertiary amine moieties.

Protonation and ion exchange equilibria of weak base anion-exchange resins

Polymercomposition and morphology can affect the way polymersinteract with biomolecules, cell membranes, and intracellular components.Herein, diblock, triblock, and statistical polymers that varied incharge center type (primary and/or tertiary amines) were synthesizedto elucidate the role of polymer composition on plasmid DNA complexation,delivery, and cellular toxicity of the resultant polyplexes. The polymerswere synthesized via RAFT polymerization and were composed of a carbohydratemoiety, 2-deoxy-2-methacrylamido glucopyranose (MAG), a primary aminegroup, N-(2-aminoethyl) methacrylamide (AEMA), and/ora tertiary amine moiety, N,N-(2-dimethylamino)ethylmethacrylamide (DMAEMA). The lengths of both the carbohydrate andcationic blocks were kept constant while the primary amine to tertiaryamine ratio was varied within the polymers. The polymers were characterizedvia nuclear magnetic resonance (NMR) and size exclusion chromatography(SEC), and the polyplex formulations with pDNA were characterizedin various media using dynamic light scattering (DLS). Polyplexesformed with the block copolymers were found to be more colloidallystable than statistical copolymers with similar composition, whichrapidly aggregated to micrometer sized particles. Also, polymers composedof a higher primary amine content were more colloidally stable thanpolymers consisting of the tertiary amine charge centers. PlasmidDNA internalization, transgene expression, and toxicity were examinedwith each polymer. As the amount of tertiary amine in the triblockcopolymers increased, both gene expression and toxicity were foundto increase. Moreover, it was found that increasing the content oftertiary amines imparted higher membrane disruption/destabilization.While both block and statistical copolymers had high transfectionefficiencies, some of the statistical systems exhibited both highertransfection and toxicity than the analogous block polymers, potentiallydue to the lack of a hydrophilic block to screen membrane interaction/disruption.Overall, the triblock terpolymers offer an attractive compositionprofile that exhibited interesting properties as pDNA delivery vehicles.

Design, synthesis and antifungal evaluation of novel benzimidazole tertiary amine type of fluconazole analogues

A micellar approach is proposed to build a series of systems featuring an "off-on-off" fluorescent window response with changes in pH. The solubilizing properties of micelles are used to self-assemble, in water, plain pyrene with lipophilized pyridine and tertiary amine moieties. Since these components are contained in the small volume of the same micelle, pyrene fluorescence is influenced by the basic moieties: protonated pyridines and free tertiary amines behave as quenchers. Accordingly, fluorescence transitions from the "off" to the "on" state, and viceversa, take place when the pH crosses the pK(a) values of the amine and pyridine fragments. To obtain an "off-on-off" fluorescent response in this investigation we use either a set of dibasic lipophilic molecules (containing covalently linked pyridine and tertiary amine groups) or combinations of separate, lipophilic pyridines and tertiary amines. The use of combinations of dibasic and monobasic lipophilic molecules also gives a window-shaped fluorescence response with changes in pH: it is the highest pyridine pK(a) and the lowest tertiary amine pK(a) that determine the window limits. The pK(a) values of all the examined lipophilic molecules were determined in micelles, and compared with the values found for the same molecules in solvent mixtures in which they are molecularly dispersed. The effect of micellization is to significantly lower the observed protonation constants of the lipophilized species. Moreover, the more lipophilic a molecule is, the lower the observed logK value is. Accordingly, changing the substituents on the basic moieties or modifying their structure, tuning the lipophilicity of the mono- or dibases, and choosing among a large set of possible combination of lipophilized mono- and dibases have allowed us to tune, almost at will, both the width and the position along the pH axis of the obtained fluorescent window.

Biosynthetically Inspired Transformation of Iboga to Monomeric Post-iboga Alkaloids

Transformation of ranitidine during water chlorination and ozonation: Moiety-specific reaction kinetics and elimination efficiency of NDMA formation potential

Among the multiple factors that induce Alzheimer’s disease, aggregation of the amyloid β peptide (Aβ) is considered the most important due to the ability of the 42-amino acid Aβ peptides (Aβ1–42) to form oligomers and fibrils, which constitute Aβ pathological aggregates. For this reason, the development of inhibitors of Aβ1–42 pathological aggregation represents a field of research interest. Several Aβ1–42 fibrillization inhibitors possess tertiary amine and aromatic moieties. In the present study, we selected 26 compounds containing tertiary amine and aromatic moieties with or without substituents and performed theoretical studies that allowed us to select four compounds according to their free energy values for Aβ1–42 in α-helix (Aβ-α), random coil (Aβ-RC) and β-sheet (Aβ-β) conformations. Docking studies revealed that compound 5 had a higher affinity for Aβ-α and Aβ-RC than the other compounds. In vitro, this compound was able to abolish Thioflavin T fluorescence and favored an RC conformation of Aβ1–42 in circular dichroism studies, resulting in the formation of amorphous aggregates as shown by atomic force microscopy. The results obtained from quantum studies allowed us to identify a possible pharmacophore that can be used to design Aβ1–42 aggregation inhibitors. In conclusion, compounds with higher affinity for Aβ-α and Aβ-RC prevented the formation of oligomeric species.

Synthesis, characterization and photophysical-theoretical analysis of compounds A-π-D. 1. Effect of alkyl-phenyl substituted amines in photophysical properties

In this paper we propose a new postcolumn detection method for compounds having primary, secondary, and tertiary amine moieties. The primary and secondary amine are delivatized by a reaction with epichlorohydrin having an epoxy moiety in a reaction coil to yield a tertiary amine with subsequent chemiluminescence detection using [Ru(bpy)3]3+. The liner values of the calibration curves of monoethanolamine (MEA), diethanolamine (DEA) and triethanolamine (TEA) were 0.02 - 1.0 nmol (r2 = 0.9986), 0.02 - 0.5 nmol (r2 = 0.9993) and 0.1 - 1.0 nmol (r2 = 0.9482), respectively. Also, the detection limits (S/N = 3) of MEA, DEA and TEA were 30, 25 and 40 pmol, respectively. The amount of DEA and TEA in shaving cream (60 microg/20 microL) were found to be 0.3 nmol and 14 nmol, respectively, by the proposed method.

The ureido moiety stands as one of the most regarded scaffolds in medicinal and organic synthesis. In this study, we endeavored to synthesize a product containing tertiary amine moieties through the nucleophilic substitution reaction of the 2-chloroethyl urea derivative with a secondary amine, utilizing either inorganic bases, such as K<sub>2</sub>CO<sub>3</sub> or organic bases like triethylamine as acidbinding agents in diverse reaction media. Unfortunately, the reaction failed to yield the desired nucleophilic substitution product in high yield, attributed to the reactivity of the 2-chloroethyl urea derivative. The structures of potential impurities were elucidated based on comprehensive spectroscopic data, including ¹H NMR, ¹³C NMR, HRMS, HMBC, and HSQC.

Integrated CO2 capture and hydrogenation to produce formate offers a sustainable approach for reducing carbon dioxide emissions and producing liquid hydrogen carriers (formate) simultaneously. In the current study, three different types of aqueous amine solutions including monoethanolamine (MEA), diethanolamine (DEA) and triethanolamine (TEA) were investigated as CO2-capturing and hydrogenation agents in the presence of a Pd/NAC catalyst. The effect of amine structures on the CO2 absorption products and formate yield was investigated thoroughly. It was found that the formate product was successfully produced in the presence of all three aqueous amine solutions, with tertiary amine TEA accounting for the highest formate yield under the same CO2 loadings. This is due to the fact that primary and secondary amine moieties in MEA and DEA are responsible for the formation of CO2 adducts of carbamate and bicarbonate, whereas the tertiary amine moiety in TEA is responsible for the formation of hydrogenation-favorable bicarbonate as the solo CO2 absorption product. A high yield of formate of 82.6% was achieved when hydrogenating 3 M TEA with 0.3 mol CO2/mol amine solution in the presence of a Pd/NAC catalyst. In addition, the physio-chemical properties of the Pd/NAC catalyst analyzed using TEM, XRD and XPS characterization were applied to rationalize the superior catalytic performance of the catalyst. The reaction mechanism of integrated CO2 capture and hydrogenation to produce formate in aqueous amine solutions over Pd/NAC catalyst was proposed as well.

The alkali metal- and ammonium picrate extracting ability of d-glucose- and d-mannose-based 15-crown-5 ethers and related lariat ethers was investigated in dichloromethane – water system. A heteroatom was waried in the crown ether containing a 4,6-O-benzylidene-α-d-glucopyranoside unit 6, (X=O), 2 (X=S) and 8a (X=NH). Extracting ability of the latter species (8a) was excellent (97–99%) in regard of all cations (Li+, Na+, K+, Rb+, Cs+ and NH4+) examined, it was not, howewer, selective. Introduction of a side arm on the nitrogen atom of 8a decreased the extracting ability, but increased the selectivity. In this series of compounds (8b–f, 4), 4 with a pyridylethyl substituent allowed the extraction of sodium picrate in 72%. The glucose-based macrocycles 8a, 8e and 8f formed a stronger complex with the cations examined than the mannose-based analogues 9a, 9e and 9f, that can be explained by the all-gauche conformation of the former ones. It was pointed out that in the case of crowns with tertiary amine moieties, the basicity increases the quantity of the picrates extracted. According to complex forming measurements by FAB-MS, the best sodium ion selectivity was achieved by the γ-hydroxypropyl substituted lariat ether (8e). Possible structures of the complexes formed by the two types of monosacharides with sodium cation were evaluated by molecule modelling calculations.

Electropolymerization of phenothiazine, phenoxazine and phenazine derivatives: Characterization of the polymers by UV-visible difference spectroelectrochemistry and Fourier transform IR spectroscopy

In designing amine-incorporated adsorbents for CO2/CH4 separation, it is essential to understand the individual effects amine moieties have on the separation of CO2/CH4 mixtures. In this work, primary, secondary, and tertiary amines are moderately grafted on SBA-15 to examine factors affecting adsorption of CO2 and CH4. Materials were characterised by thermogravimetric and elemental analysis, and their performance was measured by volumetric and gravimetric gas adsorption. An amine density of 1.6–1.7 mmol/g in secondary and tertiary amines showed an equivalent CH4 uptake of <0.04 mmol/g at 25 °C, while primary amines adsorbed 0.05 mmol/g, indicating stronger interaction forces with CH4. In terms of selectivity, primary and secondary amines grafted at 1.3–1.4 mmol/g had similar values, unaffected by amine type. Adsorption results cross analysed with DFT simulations indicate similar binding energies for CH4 by both amine moieties, concluding the facilitated access of gas molecules to primary amine moieties is the primary factor dictating degree of adsorption. At an amine density of ∼ 1.7 mmol/g for both primary and secondary amines, an increase in temperature from 25 to 40 °C at a CO2 partial pressure of 40 kPa showed a decrease in CO2/CH4 selectivity of only primary amines. Secondary amines are thus more selective amine moieties at these conditions. Furthermore, in isothermal adsorption–desorption conditions, moderately grafted secondary amines have an equal working capacity to primary amines. Both these qualities support secondary amines at moderate densities as candidates for adsorbent development in CO2/CH4 separations.