Ternary Amine Research Articles

Molecular Tuning of a Vitamin E-Scaffold pH-Sensitive and Reductive Cleavable Lipid-like Material for Accelerated in Vivo Hepatic siRNA Delivery.

A lipid nanoparticle (LNP) composed of a series of SS-cleavable and pH-activated lipid-like materials (ssPalm) was previously developed as a platform of a gene delivery system. A tertiary amine and disulfide bonding were employed to destabilize the endosomal membrane and for intracellular collapse. We report herein on the development of a hepatocyte-targeting siRNA carrier by the molecular tuning of the hydrophobic scaffold, and tertiary amine structures. The gene knockdown activity against a hepatocyte-specific marker (factor VII: FVII) was improved when a more fat-soluble vitamin (vitamin E) was employed as a hydrophobic scaffold. Moreover, to allow the tertiary amines to accept protons by sensing a slight change in endosomal acidification, its structural flexibility was minimized by fixing it in a piperidine structure, and the distance between the surface of the particle to the ternary amine was increased. As a result, the pKa value was increased to the approximately 6.18 depending on its distance, while the pKa reached plateau when the tertiary amine was linked by an excess number of linear carbon chains. The pH-dependent membrane destabilization activity, as assessed by a hemolysis assay, was increased in parallel with the pKa value. Moreover, the gene knockdown activity was improved in parallel with hemolytic activity. Finally, further optimization of the lipid/siRNA ratio, and the use of chemically (2'-fluoro) modified siRNA synergistically improved the gene knockdown efficacy to an effective dose (ED50) of 0.035 mg/kg. The developed ssPalm represents a promising platform for use as a hepatocyte-targeting siRNA carrier.

Influence of sol–gel conditions on the final structure of silica-based precursors

This work studied the solvent-free sol–gel process of (3-glycidyloxypropyl)trimethoxysilane using three different experimental setups and a ternary amine (DABCO) or a tin-based compound (DBTL) as the sol–gel catalysts, which allowed to prepare homogeneous liquid products and control their final microstructures. The aim was to synthesize epoxy-functionalized precursors for hybrid epoxy-based materials. The NMR spectroscopy, MALDI-TOF, DLS, FTIR and SEC were used to characterize the obtained sols and xerogels. The formed silica structures were primarily dependent on the type of catalyst used, but small cyclic structures were always present. Nevertheless, the DABCO-catalyzed system showed a higher tendency to create cage-like structures in contrast to the system that used DBTL catalyst in which larger ladder-like structures prevailed. The sols as well as the final xerogels with the higher condensation degree of alkoxysilane bonds were prepared under the basic (DABCO) conditions. All prepared liquid products (sols) were well miscible with epoxy pre-polymers and therefore can be considered as suitable epoxy-functionalized precursors for preparation of hybrid materials based on epoxy matrix.

A neutral lipid envelope-type nanoparticle composed of a pH-activated and vitamin E-scaffold lipid-like material as a platform for a gene carrier targeting renal cell carcinoma

A renal cell carcinoma (RCC) is one of the refractory tumors, since it readily acquires resistance against chemotherapy. Thus, alternative therapeutic approaches such as obstructing the neovasculature are needed. We previously reported on the development of a plasmid DNA (pDNA)-encapsulating liposomal nanoparticle (LNP) as a hepatic gene delivery system that is applicable to systemic administration. The key molecular component is a SS-cleavable and pH-activated lipid-like material (ssPalm) that mounts dual sensing motifs (ternary amines and disulfide bonding) that are responsive to the intracellular environment. The main purpose of the present study was to expand its application to a tumor-targeting gene delivery system in mice bearing tumors established from a RCC (OS-RC-2). When the modification of the surface of the particle is optimized for the polyethyleneglycol (PEG), stability in the blood circulation is improved, and consequently tumor-selective gene expression can be achieved. Furthermore, gene expression in the tumor was increased slightly when the hydrophobic scaffold of the ssPalm was replaced from the conventionally used myristic acid (ssPalmM) to α-tocopherol succinate (ssPalmE). Moreover, tumor growth was significantly suppressed when the completely CpG-free pDNA encoding the solute form of VEGFR (fms-like tyrosine kinase-1: sFlt-1) was used, especially when it was delivered by the LNP formed with ssPalmE (LNPssPalmE). Thus, the PEG-modified LNPssPalmE is a promising gene carrier for the cancer gene therapy of RCC.

Electrical Conductivity of SiOCN Ceramics by the Powder‐Solution‐Composite Technique

SiOCN ceramics have been prepared by the polymer pyrolysis method. The preceramic polymers were synthesized from a polysiloxane cross‐linked with two different N‐containing compounds: a silazane or a ternary amine. The corresponding SiOCN ceramics were obtained by pyrolysis in nitrogen atmosphere at five different temperatures from 1000°C to 1400°C. The electrical conductivity of the powdered SiOCN ceramic samples was determined by the powder‐solution‐composite technique. The results show an increase in room temperature AC conductivity of three orders of magnitude, from ≈10−5 (S/cm) to ≈10−2 (S/cm), with increasing pyrolysis temperature from 1000°C to 1400°C. Furthermore, the electrical conductivity of the amine‐derived SiOCN is three to five times higher than that of the silazane‐derived ceramic at each pyrolysis temperature. The combined structural study by Raman spectroscopy and chemical analysis suggests that the increase of electrical conductivity with the pyrolysis temperature is due to the sp3‐to‐sp2 transition of the amorphous carbon phase. The higher conductivity of the amine‐derived SiOCN is also discussed considering features like the volume% of the free‐carbon phase and its possible N‐doping.

OH⋅⋅⋅N and CH⋅⋅⋅O Hydrogen Bonds Control Hydration of Pivotal Tropane Alkaloids: Tropinone⋅⋅⋅H2O Complex

The effect of monohydration in equatorial/axial isomerism of the common motif of tropane alkaloids is investigated in a supersonic expansion by using Fourier-transform microwave spectroscopy. The rotational spectrum reveals the equatorial isomer as the dominant species in the tropinone⋅⋅⋅H2 O complex. The monohydrated complex is stabilized primarily by a moderate OH⋅⋅⋅N hydrogen bond. In addition, two CH⋅⋅⋅O weak hydrogen bonds also support this structure, blocking the water molecule and avoiding any molecular dynamics in the complex. The water molecule acts as proton donor and chooses the ternary amine group over the carbonyl group as a proton acceptor. The experimental work is supported by theoretical calculations; the accuracy of the B3LYP, M06-2X, and MP2 methods is also discussed.

Preparation of heterogeneous cationic metalloporphyrin/heteropolyanion composite catalysts and their high catalytic activity in hydroxylation of cyclohexane with molecular oxygen

A new route to improve the metalloporphyrin catalysts is developed, and it is to constitute heterogeneous composite catalysts with immobilized cationic metalloporphyrins and heteropolyanions. By using the method of synchronously synthesizing and immobilizing porphyrins on cross-linked polystyrene microspheres (CPS microspheres), the immobilized porphyrin TAPP-CPS microspheres, on which ternary amine (TA) group-containing phenyl porphyrin (PP) was immobilized, were first prepared, and then the immobilized cationic porphyrin TMPP-CPS microspheres, in whose structure trimethylammoniophenyl porphyrin (TMPP) was contained, were obtained via quaternization reaction. Finally, three immobilized metalloporphyrins, CoTMPP-CPS (shorten as CoP-CPS), MnTMPP-CPS (MnP-CPS) and FeTMPP-CPS (FeP-CPS), were gained through coordination reactions. These immobilized metalloporphyrins were composited with heteropolyanions by right of the mutual electrostatic interaction with phosphotungstic (PW) acid and phosphomolybdic (PMo) acid as reagents, respectively, resulting in several heterogeneous metalloporphyrin/heteropolyanion composite catalysts such as CoPPW-CPS, CoPPMo-CPS and MnPPW-CPS. The composite catalysts were used in the catalytic hydroxylation reaction of cyclohexane with molecular oxygen as oxidant, and their catalytic performances were investigated. The experimental results show that the heterogeneous composite catalysts have extraordinarily high catalytic activity in the hydroxylation reaction of cyclohexane by molecular oxygen, and the cyclohexanol yield in 8 h can get up to 45.5 %. More importantly, the catalytic activity of the heterogeneous composite catalysts is obviously higher than that of the immobilized cationic metalloporphyrins, and the enhanced catalytic activity is originated from a protection of heteropolyanions against the deactivation of metalloporphyrins.

Characterizing the Transport Properties of Multiamine Solutions for CO2 Capture by Molecular Dynamics Simulation

We performed molecular dynamics (MD) simulations on multiamine solutions of CO2 capture to optimize the conventional amine solvents (MEA, MDEA, DEA, AMP, and TEA). A synergy molecular dynamics model (SMD) was developed for the CO2 and amine solutions, in which the molecular synergy number (MSN) was introduced to quantify interactions between diffusion and molecule motion. The SMD model involved with the force field was validated with experimental data from CO2, amine, and water systems. The best synergy for the MDEA-DEA-TEA system was achieved at the ratio of 3:1:1, with a minimum MSN being 3.89. The overall synergy in ternary amine systems was found to be better than that in quaternary and quintuple amine systems. Several optimized multiamine solution systems were identified. The MDEA-DEA-TEA solution could simultaneously provide better diffusivity and less drag force with mass transfer coefficient being 33.33 % higher than that of AMP. The MEA-MDEA-DEA-TEA solution could improve CO2 transport by increasing 18 % of diffusivity when varying the ratio from 1:1:1:1 to 2:1:1:1. All of the results above provided a benchmark to optimize the amine mixing solution design for CO2 capture.

Diameter-dependent photocatalytic performance of niobium pentoxide nanowires

Thermal reactions of a niobium oxo-oxalate complex, (NH4)3[NbO(Ox)3]·H2O, with ternary amines having more than two methylene chain units as structure directing solvents led to self-assemblies suitable for one dimensional growth to afford amorphous niobium oxide nanowires whose diameters depended on methylene chain lengths in the amines. These nanowires were crystallized at 773 K to obtain the TT phase of Nb2O5 whilst maintaining the same structure as before calcination. There was almost no difference in crystallinities, BET surface areas, and growth directions among the Nb2O5 nanowires. PtCl6(2-) was reduced by photogenerated electrons in the conduction band of the Nb2O5 nanowires following UV light irradiation (λ > 300 nm) in the presence of an electron donor. Metallic Pt nanoparticles were selectively deposited on a short axis plane of the nanowires prepared with tridodecylamine, whereas the others had the Pt nanoparticles throughout the surfaces. This indicated that photogenerated electrons moved along the nanowire growth direction associated with transfer of holes to the nanowire sidewall. The anisotropic carrier transport afforded the highest activity for photocatalytic H2 evolution reactions under UV light irradiation (λ > 300 nm).

Synthesis, Crystal Structure, and Cytotoxic Property of bis(5-Chloro-2-nitrobenzoato)bis(2-piperidin-1-ylethylamine)disilver(I)

5-Chloro-2-nitrobenzoic acid reacts with silver oxide and 2-piperidin-1-ylethylamine to give a centrosymmetric dinuclear silver(I) complex, [Ag2(C7H3ClNO4)(C7H16N2)2]. The complex was characterized by elemental analysis and X-ray diffraction. The two Ag atoms are bridged by two 2-piperidin-1-ylethylamine ligands, generating a 10-membered chelate ring. The distance between the two Ag atoms is 2.948(2) Å. Each Ag atom in the complex is three-coordinated by one primary amine and one ternary amine N atoms from two symmetry-related 2-piperidin-1-ylethylamine ligands, and by one carboxylate O atom of a 5-chloro-2-nitrobenzoate ligand, forming a distorted Y-shaped coordination. In the crystal structure, the molecules are linked through intermolecular N–H···O hydrogen bonds, forming chains running along the a-axis. The complex shows effective cytotoxic property to both carcinoma and normal cells.

Effect of amide moieties for hydrogelators on gelation property and heating-free pH responsive gel-sol phase transition

Two long-chain amidoamine derivatives (C13A2AOH and C17A2AOH) bearing three amide moieties were synthesized and their gelation ability and pH responsivity were compared with a similar, previously reported amidoamine derivative gelator with two amide moieties. C13A2AOH and C17A2AOH gels prepared in water and organic solvents acted as ambidextrous low molecular mass gelators. X-ray diffraction and Fourier transform infrared spectroscopy analyses revealed that C13A2AOH and C17A2AOH formed lamellar-like aggregates in the gels, where the amide moieties were in a strong intermolecular hydrogen-bonding state. The gelation ability, i.e., the molar ratio of solvent to gelator, was significantly dependent on the length of the alkyl chain and the number of amide moieties. In addition, the C13A2AOH and C17A2AOH hydrogels exhibited highly pH-responsive gel-sol transitions. The gel-sol transition for the hydrogels was induced by protonation of the ternary amine and the transition was completely reversible by regulating only the pH without heating.

The Henry's law constant of N 2O and CO 2 in aqueous binary and ternary amine solutions (MEA, DEA, DIPA, MDEA, and AMP)

This paper presents a new expression for the Henry's law constant of N 2O in aqueous binary and ternary amine solutions (monoethanolamine MEA, diethanolamine DEA, diisopropanolamine DIPA, N-methyldiethanolamine MDEA, and 2-amino-2-methyl-1-propanol AMP) as a function of temperature and amine concentration. The Henry's law constant of CO 2 is derived from the Henry's law constant of N 2O in the same solvents, assuming the N 2O–CO 2 analogy. The Henry's law constant of CO 2 in aqueous amine solvents is necessary while modeling gas sweetening and post-combustion CO 2 capture processes, i.e. the absorber and the solvent regeneration units. The parameters of the new expression were fitted to 992 data points up to 393 K, thus extending the model validity range to higher temperatures compared to most of the models found in the literature. The Henry's law constants at high temperatures are especially important in modeling the solvent regeneration step, since amine regenerations often occurs near 393 K, which is above the validity range of most existing correlations. The weighted average error calculated on all the studied binary solvents was 5%. The shape of our model enables the direct calculation of the Henry's law constant of N 2O in aqueous ternary amine solutions solely based on the Henry's law constants of N 2O in aqueous binary amine solutions with an average deviation of 9.4%. If solubility data in the aqueous ternary amine solutions of interest are available, an additional ternary parameter can be regressed and the model average error reduced to 6.4%.

Photosensitive micelles based on polysiloxanes containing azobenzene moieties

Photosensitive micelles based on amphiphilic azo-polysiloxanes were obtained and characterized. The amphiphilic polymers were synthesized in a two-step reaction, starting from a polysiloxane containing chlorobenzyl groups in the side chain. In the first step, the polysiloxane was modified with azo-aromatic groups (35–45% substitution degree) and in the second step the unreacted chlorobenzyl groups were quaternized, using different tertiary amines. The structure of the polysiloxanes and their aggregation/disaggregation capacity were evaluated by 1H-NMR, DSC, fluorescence and UV–VIS spectroscopy, dynamic light scattering and transmission electron microscopy. All the amphiphilic polysiloxanes are capable of generating micelles, the critical concentration of the aggregation values being situated in the range 10−3–10−2 g/L. As a function of the ternary amine structure used in the quarterisation reaction, the micellar aggregation process is different, individual micelles or micellar clusters being obtained. The clusters' dimension cannot be controlled, the polydispersity index having high values. The disaggregation processes of the micelles under UV irradiation reveal that the polymer chemical structure influences the aggregates stability. A total micelles disaggregation was obtained for the polysiloxane modified with azophenol and amine containing a long hydrocarbon segment. In the other cases, only a partially disaggregation process takes place.

End-Group-Catalyzed Ring-Opening Polymerization of Trimethylene Carbonate

A controlled self-catalyzed polymerization reaction yielding well-defined heterotelechelic polymer chains and eliminating low molecular weight catalyst residues in the final polymer product were analyzed by utilizing a ternary amine. The molecular weights were kept relatively low for end-group analysis by Nuclear Magnetic Resonance spectroscopy (NMR) and linear correlation between the degree of polarization and monomer were found. NMR results show that the polydispersities remained low at high monomer conversions and longer reaction times after full conversion led to a larger molecular weight distribution. The results also show that the ternary amine catalyst are attached to the growing polymer chains that is shown by a downfield shift from 2.44 to 2.56 ppm. The benzoic acid ester of the ternary amine is found to be potent catalyst of Ring-Opening Polymerization (ROP).

Different Flocculation Behaviors Between Ternary‐Amine Polystyrene Latex and Poly(styrenesulfonate): Probe Charge Effect

AbstractThe flocculation of strong polyelectrolyte, poly(styrene sulfonate), (PSS) with ternary amine‐functionalized polystyrene particles was investigated by dynamic light scattering (DLS). Ternary amine particles that show stable dispersion in pH 10 undergo different flocculation in a low pH conditions. In pH 3 condition, particles present fast aggregation and irreversible process (coagulation) but in pH 7 solution particles show slow aggregation and reversible process (depletion‐induced flocculation). By adding strong polyelectrolyte, aggregation rapidly removed in pH 7 but retained some concentration (about 5 mg/L) in pH 3. The homogeneity exponent λ to characterize the different flocculation behaviors presents not only difference as a function of pH but also distinction as a function of concentration in pH 3.

Versatile synthetic approach to new bifunctional chelating agents tailor made for labeling with the fac-[M(CO) 3] + core (M = Tc, 99mTc, Re): synthesis, in vitro, and in vivo behavior of the model complex [M(APPA)(CO) 3] (appa = [(5-amino-pentyl)-pyridin-2-yl-methyl-amino]-acetic acid)

A general synthetic approach for potent tridentate, bifunctional chelating agent (BFCA) for the [M(CO) 3] + fragment (M = 99gTc, 99mTc, and Re) has been elaborated. The strategy allows the facile preparation of BFCA with a pendent amino or carboxylic acid functionality for coupling to peptides and proteins via formation of an amide bond. [(5-amino-pentyl)-pyridin-2-yl-methyl-amino]-acetic acid (APPA) and [pyridin-2-yl-methyl-amino]-diacetic acid (PADA) were synthesized according to this protocol. The BFCA were labeled with the [M(CO) 3] + fragment, which resulted in formation of uniform products with a ligand to metal ratio of 1:1. The complexes have been fully characterized by means of mass spectrometry, IR, and NMR ( 1H, 13C, 99Tc) spectroscopy. Coordination of the tricarbonyl core with APPA and PADA was exclusively tridentate (via the acid function, the ternary amine, and the pyridine nitrogen). On the n.c.a. level the complexes were almost quantitatively formed (yield >90%) at ligand concentrations of 10±2 μM (PADA) or 50±4 μM (APPA) after 30 min at 70°C. Chromatographic behavior of the 99mTc complexes is similar to that of the corresponding 99Tc/Re complexes suggesting the identical chemical structure. Pharmacokinetic experiments with the 99mTc-APPA complex were performed in BALB/c mice and compared with previously published results of the 99mTc-PADA complex. The 99mTc-APPA complex revealed good clearance from the blood pool (0.29 ± 0.03% ID after 24h p.i.) and a low uptake in the liver (2.41 ± 0.14% ID/g), in the kidneys (2.81 ± 0.12% ID/g) and other tissue and organs.

Extraction Equilibrium of Precious Metals from Aqueous Acidic Solutions Using Divinylbenzene Homopolymeric Microcapsules Encapsulating Ternary Amine as a Core Material

Divinylbenzene homopolymer microcapsules having porous membranes encapsulating tri‐n‐octylamine as a core material were prepared by in‐situ polymerization accompanied by the evaporation of toluene. The extraction equilibria of hydrochloric acid and precious metals in an acidic solution using the prepared microcapsules were measured at 303 K. The addition of toluene into the dispersed phase resulted in the microcapsule membrane having a porous structure due to the toluene evaporation during in‐situ polymerization, which was verified based on the results obtained both from SEM observation of the microcapsules' morphology and in the extraction equilibrium of hydrochloric acid. Using microcapsules prepared with toluene, hydrochloric acid was sufficiently extracted form an aqueous solution. In contrast, microcapsules prepared without toluene scarcely extracted hydrochloric acid. The microcapsules successfully extracted palladium(II) from the acidic media, and this was explained by the reaction between one palladium ion and two molecules of tri‐n‐octylamine in a similar manner of that taking place in the solvent extraction. The back‐extraction of palladium(II) from the microcapsules was expressed by the back‐reaction of the extraction. Gold(III) and platinum(IV) were also successfully extracted using the prepared microcapsules.

A novel macroinimer of polyethylene oxide: synthesis of hyper branched networks by photoinduced H-abstraction process

A novel poly(ethylene oxide) macroinimer (PEO-macronimer) possesing methacryloyl and tertiary amino end groups was prepared by ring-opening polymerization of ethylene oxide initiated by potassium 2-methylaminoethoxide and termination of living ends of PEO with methacryloyl chloride. NMR analysis showed that the macronimer contains equal amount of amino and methacrolyl groups indicating efficient initiation and termination processes. The dimethylamine end group in conjunction with benzophenone under UV irradiation produced ternary amine methylene radicals via H-abstraction mechanism which initiates the polymerization. Photopolymerization in solutions at high macroinimer concentration or in films resulted in the formation of insoluble networks. The crosslinked polymers exhibit high swelling capacity in organic solvents and water due to the hyperbranched nature.

Preparation of a copolymer of methyl methacrylate and 2-(dimethylamino)ethyl methacrylate with pendant 4-benzyloxy-2,2,6,6-tetramethyl-1-piperidinyloxy and its initiation of the graft polymerization of styrene by a controlled radical mechanism

The macroinitiator of a copolymer (PMD BTM ) of methyl methacrylate (MMA) and 2-(dimethylamino)ethyl methacrylate (DAMA) with 4-benzyloxy-2,2,6,6-tetramethyl-1-piperidinyloxy (BTEMPO) pendant groups was prepared by the photochemical reaction of tertiary amine groups of the copolymer with benzophenone in the presence of BTEMPO. The radical copolymerization of MMA and DAMA was carried out first with azo-bis-isobutyronitrile (AIBN) as an initiator; then, the dimethylamine groups of the copolymer constituted a charge-transfer complex with benzophenone under UV irradiation, and the methylene of ternary amine and diphenyl methanol radicals were produced. The former was capped by BTEMPO, and the nitroxide (BTEMPO) was attached to the polymeric backbone. The amount of pendant BTEMPO on PMD BTM was measured by 1 H NMR. PMD BTM initiated the graft polymerization of styrene via a controlled radical mechanism, and the molecular weight of the PMD-g-polystyrene increased with the polymerization time.

The nature of the binding of high-molecular weight aminoammonium and quaternary ammonium salts with the amorphous silica surface

The adsorption of high-molecular weight aminoammonium salt (C 10H 21) 2N(CH 2) 2N(C 10H 21) 3I and quaternary ammonium salts with different structure of hydrophilic and hydrophobic areas: (CH 3)(C 10H 21) 2N(CH 2) 2N(C 10H 21) 3I 2, (C 10H 21) 3N(CH 2) 6N(C 10H 21) 3I 2 and (C 2H 5) 4NBr on amorphous silica (SG) has been investigated. The surface hydrate coating parameters of modified SG have been studied by the 1H NMR spectroscopy technique applied to the frozen suspensions. The data obtained were used for identification of the nature of the modifying agent binding with SG surface. It was shown that beside dipole–dipole intramolecular dispersive interaction plays an essential role in high-molecular weight salts immobilization on SG surface. The binding of aminoammonium salt with the surface is also a result of hydrogen bound complexes formation between ternary amine nitrogen of salt and surface hydroxyl group.

Synthesis and Characterization of a Novel Macroinitiator of Poly(ethylene oxide) with a 4-Hydroxy-2,2,6,6-tetramethylpiperidinyloxy End Group: Initiation of the Polymerization of Styrene by a “Living” Radical Mechanism

A novel macroinitiator of poly(ethylene oxide) (PEO) with a 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (HTEMPO) end group (PEOHTM) was prepared by the photochemical reaction of a tertiary amine end group of PEO with benzophenone (BP) in the presence of HTEMPO. Potassium 2-dimethylaminoethoxide was used to initiate the ring-opening polymerization of ethylene oxide first, then the dimethylamine end group of PEO constituted the charge-transfer complex with BP under UV irradiation, and finally ternary amine methylene and diphenyl methanol radicals were formed. The former reacted with HTEMPO to form the desired product. PEOHTM can initiate the polymerization of styrene by a “living” radical mechanism. The molecular weight of the PS block increased with the polymerization time, and the molecular weight distribution (Mw/Mn) was less than 1.5, even though the molecular weight of the former was as high as 2 × 105. The DSC measurement of the copolymer confirmed that the Tg of the PS block was 106 °C, which was 6 t...