Pendant Amine Research Articles

Synthesis of acrylic copolymers consisting of multiple amine pendants for dispersing pigment

A class of acrylic copolymers with narrow molecular weight distribution from butyl methacrylate and glycidyl methacrylate comonomers via atom transfer radical polymerization was synthesized. Various types of polarities including hydroxyl-amines, glycols, and carboxylic acids were then grafted onto the oxirane side groups. The resultant comb-like copolymers with different polar pendants were tested for homogenizing a representative Yellow pigment in 1,6-hexanediol diacrylate medium. Specifically, the polyacrylates with 1,3-diamine pendants (7–10 multiplicity on each polymer strain) enabled to homogeneously disperse the pigment than the analogous copolymers with hydroxyl or carboxylic acid groups. Ultimately, the pigment dispersion with an average size of ca. 20 nm in diameter, high transmittance and low viscosity was achieved. Furthermore, the pigment dispersion was allowed to UV-cure into a film, and for the first time, the primary structures of the pigment particles (ca. 50 nm in diameter) were observed by transmission electronic microscope.

Synthesis of di‐ and tri‐tertiary amine containing methacrylic monomers and their (co)polymerization via RAFT

AbstractThe synthesis, reversible addition‐fragmentation chain transfer (RAFT) (co)polymerization, and aqueous phase behavior of three methacrylic monomers containing two or three pendent tertiary amine functional groups are described. Homopolymerizations were conducted with 1‐methyl‐1‐cyanoethyl dithiobenzoate (CPDB) under bulk conditions following standard RAFT procedures. All three monomers, 1,3‐bis(dimethylamino)propan‐2‐yl methacrylate (M1), 1‐(bis(3‐(dimethylamino)propyl) amino)propan‐2‐yl methacrylate (M2), and 2‐((2‐(2‐(dimethylamino)ethoxy)ethyl) methylamino)ethyl acrylate (M3), polymerized in a controlled manner as evidenced by the kinetic and molecular weight profiles. Homopolymerizations conducted at a lower ratio of CPDB:AIBN proceeded faster than those at a higher ratio. Subsequently, the facile copolymerization behavior of M1 and M3 was demonstrated via the synthesis of a range of statistical copolymers with hexyl and lauryl methacrylate comonomers containing 10–90 mol % hydrophobic comonomer. Finally, the aqueous‐solution characteristics of the M1–M3 homopolymers were briefly examined. All three homopolymers were shown to undergo phase transitions in aqueous media in response to changes in both temperature and pH. Specifically, 1 wt % solutions of polyM1 were shown to possess an LCST of ∼22 °C, that of polyM2 at ∼33 °C, and for polyM3 the observed cloud point was ∼63 °C. Additionally, all homopolymers became hydrophobic and phase separated at high solution pH. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1877–1890, 2009

Enantioselective Synthesis of Schulzeines B and C via a β-Lactone-Derived Surrogate for Bishomoserine Aldehyde

Enantioselective syntheses of the glucosidase inhibitors schulzeines B and C were achieved by employing a Pictet-Spengler reaction of a beta-lactone-derived, masked bishomoserine aldehyde. Subsequent Corey-Link reaction unveiled an alpha-azido acid enabling cyclization to the delta-lactam fused tetrahydroisoquinoline. An efficient synthesis of the trisulfate-bearing side chain featured a Noyori hydrogenation and a Sharpless dihydroxylation. An unexpected reaction of a pendant amine during a Corey-Link process opens avenues for the synthesis of proline and related amino acid derivatives.

Influence of a Pendant Amine in the Second Coordination Sphere on Proton Transfer at a Dissymmetrically Disubstituted Diiron System Related to the [2Fe]H Subsite of [FeFe]H2ase

Studies of the protonation of [Fe2(CO)4(kappa2-PNP)(mu-pdt)] (1; PNP = (Ph2PCH2)2NCH3) by HBF4.Et2O showed that the nature of the reaction product depends on whether the reaction is conducted in acetone or in dichloromethane. In acetone, an N-protonated form, 2, is isolated. Tautomerization of 2 in CH2Cl2 gives rise to a mu-hydride species 3. Variable-temperature NMR experiments have been performed to clarify the processes involved.

Copolymerization of Styrene and Ethylene at High Temperature with Titanocenes Containing a Pendant Amine Donor

The copolymerization of ethylene and styrene at 120 °C was investigated with a series of titanocenes: Cp′TiCl2L [1, 2: Cp′ = cyclopentadienyl (Cp) versus 3, 4: Cp′ = {2-(dimethylamino)ethyl}cyclopentadienyl (CpN); 1, 3: L = Cl versus 2, 4: L = 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)], in combination with methylaluminoxane (MAO). At 120 °C, titanocenes bearing a pendant amine ligand (3 and 4) are effective catalysts for the ethylene-styrene (ES) copolymerization, whereas complexes lacking the pendant group (1 and 2) afford only mixtures of polyethylene (PE) and atactic polystyrene (aPS). At these temperatures, copolymerization with complexes 3 and 4 yields mixtures of ES copolymers and atactic polystyrene that are not readily separated by solvent extraction or gel permeation chromatography as both components of the mixture exhibit similar molecular weights and solubility in THF and acetone. The source of the atactic polystyrene was the autopolymerization of styrene as deduced by carrying out the copolymerization in the presence of a catalytic chain transfer agent, cobalt tetraphenylporphyrin (Co(tpp)). The addition of Co(tpp) caused a decrease in the molecular weight of the atactic polystyrene but had no effect on the molecular weight of the ES copolymer.

Syntheses, characterization, and functionalization of poly(ester amide)s with pendant amine functional groups

AbstractPoly(ester amide)s (PEAs) comprising α‐amino acids, diols, and diacids are promising materials for biomedical applications such as tissue engineering and drug delivery because of their tunability and potential for either hydrolytic or enzymatic degradation. Although a number of PEAs of different compositions have been reported, there is a significant need for the incorporation of amino acids with functional side chains. This will allow for the conjugation of drugs or cell signaling molecules in tissue engineering scaffolds, thus expanding the potential applications of these materials. The objective of this work was the incorporation of l‐lysine into PEAs to provide functionalizable pendant amine groups. Thus, varying percentages of lysine were incorporated into PEAs comprised of l‐phenylalanine, 1,4‐butanediol, and succinic acid by tuning the ratio of ε‐protected‐l‐lysine and l‐phenylalanine derived monomers. The polymers were characterized by nuclear magnetic resonance spectroscopy, infrared spectroscopy, size exclusion chromatography, and differential scanning calorimetry. The lysine ε‐protecting group was removed, then the reactivity of the pendant amines was demonstrated by reaction with amino acid and tri(ethylene glycol) derivatives. The degradation of thin films of polymers were studied using scanning electron microscopy and the incorporation of lysine was found to significantly accelerate both the hydrolytic and enzymatic degradation. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6376–6392, 2008

Three-Dimensional Patterning of Poly(Ethylene Glycol) Hydrogels Through Surface-Initiated Photopolymerization

Photopolymerizable hydrogels have been investigated extensively for biomedical applications, specifically in the area of tissue engineering. While fabrication approaches have shown promise in designing hydrogel scaffolds that guide cell function, the ability to spatially control localization in three-dimensions has been limited. We have developed a method for generating two-dimensional and three-dimensional (3D) patterns within multilayered poly(ethylene glycol) diacrylate (PEG-DA) hydrogels. Covalently attached hydrogel layers are formed using precursor solutions with a 10:1 mole ratio of PEG-DA to PEG-aminoacrylate (Acr-PEG-NH2). Upon illumination of the precursor with visible light (wavelength = 514 nm), a hydrogel layer forms with pendant amine groups induced by the presence of Acr-PEG-NH2 macromer. Pendant amine groups are further functionalized with free carboxyl groups present on the visible light photoinitiator eosin, allowing for the formation of subsequent hydrogel layers. Using noncontact photolithography, the prepolymer solution is polymerized through a photomask, resulting in hydrogel structures with distinct pattern formation in each layer. Unreacted regions immobilized with eosin can be subsequently filled with a different PEG hydrogel. The technique presented shows a great potential for tissue engineering applications, for biosensors, and in the formation of cell and protein patterning for biotechnology.

The role of pendant bases in molecular catalysts for H2 oxidation and production

Abstract The paper presents a review of recent studies of complexes of Ni(II) and Fe(II) coordinated by diphosphine ligands with amine bases incorporated into the ligand chelate rings. The role of the bases in the second coordination sphere in mediating rapid intramolecular M–H/N–H exchange as well as intermolecular exchange with protons and in promoting the coupling of proton- and electron-transfer processes has been studied. Factors that favor efficient proton relay properties for the pendant amines have been established and the information has been used to develop efficient electrocatalysts for both hydrogen oxidation and production.

2',2'-Ligation Demonstrates the Thermal Dependence of DNA-Directed Positional Control.

An oligodeoxynucleotide (ODN) containing a 2'-aminoalkylmercaptouridine was ligated chemically with another ODN containing a 2'-carboxyalkylmercaptouridine to produce a 2',2'-amide linked conjugate. Templation by a DNA hairpin resulted in ligation yields of > 95%. At room temperature, similar yields were obtained for amide ligations between pendent nucleotides located adjacent to each other or separated by three nucleotides. However, at 4 degrees C, ligation was vastly favored for the case where the pendent amine and carboxylate were attached to adjacent residues (i.e., at the 3'- and 5'-termini of the two ODNs). No reaction was observed to occur either at 4 degrees C or at room temperature between pendent nucleotides separated by 9 nucleotides. Denaturing gel electrophoresis, MALDI-TOF MS and full nuclease digestion coupled with LC-MS were used to characterize the reaction products.

2′,2′-Ligation demonstrates the thermal dependence of DNA-directed positional control

An oligodeoxynucleotide (ODN) containing a 2′-aminoalkylmercaptouridine was ligated chemically with another ODN containing a 2′-carboxyalkylmercaptouridine to produce a 2′,2′-amide linked conjugate. Templation by a DNA hairpin resulted in ligation yields of >95%. At room temperature, similar yields were obtained for amide ligations between pendent nucleotides located adjacent to each other or separated by three nucleotides. However, at 4 °C, ligation was vastly favored for the case where the pendent amine and carboxylate were attached to adjacent residues (i.e., at the 3′- and 5′-terminus of the two ODNs). No reaction was observed to occur either at 4 °C or at room temperature between pendent nucleotides separated by nine nucleotides. Denaturing gel electrophoresis, MALDI-TOF MS, and full nuclease digestion coupled with LC–MS were used to characterize the reaction products.

Synthesis and characteristic of double hydrophilic block copolymer with amine pendant chains

Novel double hydrophilic block copolymers with amine pendant chains were synthesized by polymerization of 4-vinyl benzylamine hydrochloric salt using 4,4′-azo-bis[4-cyanopentanoate poly(ethylene glycol) ester] as macroazoinitiator. The structures of the copolymers were characterized by 1H NMR, FTIR spectra and acid–base titration, GPC–MALS techniques.

Cyclopentadienyl-Silyl-Amido versus Imido Niobium Complexes. The Role of Additional Amine Functionalities: A Combined Experimental and Theoretical Study

The reaction of the chlorosilyl-substituted cyclopentadienyl niobium compound [Nb(η5-C5H4SiMe2Cl)Cl4] (1) with 1 equiv of propylenediamine or N-methylpropylenediamine in toluene in the presence of 2 equiv of NEt3 affords the cyclopentadienyl-silyl-amido-amine derivatives [Nb{η5-C5H4SiMe2-η-N(CH2)3-η-NHR}Cl3] (R = H, 3a; Me, 3b). In contrast, a similar reaction using the N,N-dimethylpropylene diamine regiospecifically yields the imido compound [Nb(η5-C5H4SiMe2Cl){N(CH2)3NMe2}Cl2] (4a). However, treatment of 1 with 3 equiv of N-methylpropylene diamine in the absence of NEt3 gives the imido complex [Nb(η5-C5H4SiMe2Cl){N(CH2)3NHMe}Cl2] (4b). The reaction of 1 with 0.5 equiv of NH2(CH2)3NH2 in the presence of 2 equiv of NEt3 proceeds with the formation of the tethered dinuclear diimido compound [{Nb(η5-C5H4SiMe2Cl)Cl2}2{μ-N(CH2)3-η-N}] (5a). Analogous dinuclear diimido compounds [{Nb(η5-C5H4SiMe2Cl)Cl2}2{μ-N(CH2)n-η-N}] (n = 4, 5b; 5, 5c) are obtained when 1 reacts with longer unsubstituted diamines NH2(CH2)nNH2 (n = 4 and 5), regardless of the reaction proportions. The transient dinuclear diamine adducts of such a process, [{Nb(η5-C5H4SiMe2Cl)Cl4}2{μ-NH2(CH2)n-η-NH2}] (n = 3, 6a; 4, 6b; 5, 6c), have been prepared and isolated when these reactions were performed in the absence of a base. All compounds have been characterized by elemental analysis and NMR spectroscopy, and the crystal structures of the complexes [Nb{η5-C5H4SiMe2-η-N(CH2)2NMe2}Cl3] (2c) and [{Nb(η5-C5H4SiMe2Cl)Cl4}(μ-NH2(CH2)4NH2)] (6b) have been determined by X-ray diffraction methods. The experimental work has been assisted by DFT calculations to determine the role played by the pendant amine group in this kind of process and the cause for the highfield shifted resonances for the cyclopentadienyl ipso-carbon in constrained-geometry complexes.

Design, synthesis and in vitro evaluation of vinyl ether type polymeric prodrugs of ibuprofen, ketoprofen and naproxen

2-(1-Propene)oxyethyl phthalimide ( 3) was synthesized from reaction of 1-(2-chloroethoxy)propene ( 2) with potassium- t-butoxide and polymerized by cationic polymerization method using BF 3·OEt 2 as an initiator at −78 °C to obtain polymer 4. Then, polymer 4 was hydrazinolized by hydrazine and gave polymer 5 containing pendent amine groups. Three non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen, ketoprofen and naproxen were covalently linked to polymer 5 through amide groups by reacting chloroacylated drugs 6a–6c with amine groups of polymer 5 to obtain three polymeric prodrugs 7a–7c. All the synthesized compounds were characterized by FT-IR, 1H and 13C NMR spectroscopy techniques. The polymer–drug conjugates were hydrolyzed in cellophane member dialysis bags containing aqueous buffered solutions (pH 1, 7.4 and 10) at 37 °C and the hydrolysis solutions were detected by UV spectrophotometer at selected intervals. The results showed that the drugs could be released by hydrolysis of the amide bonds. The release profiles indicated that the hydrolytic behavior of polymeric prodrugs strongly depends on the pH of the hydrolysis solution. The results suggested that the vinyl ether type polymers could be the useful carriers for release of profens in controlled release systems.

New organogelators based on cyclotriveratrylene platforms bearing 2-dimethylacetal-5-carbonylpyridine fragments

Gelators, compounds able to solidify solvents, and in particular hydrogelators are interesting soft materials. In this paper we have synthesized cyclotriveratrylene (CTV) platforms symmetrically end-substituted with pendent primary amines or nicotamic substituents. These non-amphiphilic structures induce self-assembly in a large variety of solvents forming robust and opaque gels. Cyclotriveratrylene gels have for the first time been formed and characterized using FT-IR and freeze fracture electron microscopy. Two hierarchical events are responsible for the gel structure. Individual fibres of 4–5 nm diameter are formed by aggregation of the functionalised CTV molecules. These fibres then further self-assemble into large ribbons several µm long and 20 to 40 nm wide. Within the ribbons the fine striations observed by FFEM are due to individual straight chains organized in a highly compacted state. Within the fibres the individual CTV molecules are held together by hydrogen bonding of the amide function as probed by infra-red spectroscopy.

Hydrogen production using cobalt-based molecular catalysts containing a proton relay in the second coordination sphere

The cobalt analogue of a highly active nickel electrocatalyst for hydrogen production has been synthesized and characterized as [Co(PPh2NPh2)2(CH3CN)](BF4)2. In the presence of triflic acid in acetonitrile solution, the complex loses one cyclic diphosphine ligand to form [Co(PPh2NPh2)(CH3CN)3](BF4)2, which has been synthesized independently and stucturally characterized. The latter complex serves as an electrocatalyst for hydrogen formation with a turnover frequency of 90 s−1 and an overpotential of 285 mV using bromoanilinium tetrafluoroborate as the acid. A similar cobalt complex with a related diphosphine ligand that does not contain a pendant base is not catalytically active, confirming an important role for the pendant amine in the catalytic reaction.

The Role of the Second Coordination Sphere of [Ni(PCy2NBz2)2](BF4)2in Reversible Carbon Monoxide Binding

The complex [Ni(PCy2NBz2)2](BF4)2, 1, reacts rapidly and reversibly with carbon monoxide (1 atm) at 25 degrees C to form [Ni(CO)(PCy2NBz2)2](BF4)2, 2, which has been characterized by spectroscopic data and by an X-ray diffraction study. In contrast, analogous Ni(II) carbonyl adducts were not observed in studies of several other related nickel(II) diphosphine complexes. The unusual reactivity of 1 is attributed to a complex interplay of electronic and structural factors, with an important contribution being the ability of two positioned amines in the second coordination sphere to act in concert to stabilize the CO adduct. The proposed interaction is supported by X-ray diffraction data for 2 which shows that all of the chelate rings of the cyclic ligands are in boat conformations, placing two pendant amines close (3.30 and 3.38 A) to the carbonyl carbon. Similar close C-N interactions are observed in the crystal structure of the more sterically demanding isocyanide adduct, [Ni(CNCy)(PCy2NBz2)2]2(BF4)2, 4. The data suggest a weak electrostatic interaction between the lone pairs of the nitrogen atoms and the positively charged carbon atom of the carbonyl or isocyanide ligand, and illustrate a novel (non-hydrogen bonding) second coordination sphere effect in controlling reactivity.

N,N-Dialkylaminostyryl dyes: specific and highly fluorescent substrates of peroxidase and their application in histochemistry

Fluorescent labeling of immuno-bound or endogenous peroxidase (PO) activity has been achieved to date by means of phenol derivatives with a low substitution degree. Here it is demonstrated that N,N-dialkylamino-styryl dyes can also act as fluorescent substrates of PO. They undergo enzymatically cross-linking reactions to surrounding cell constituents in an analogous manner thus permitting highly fluorescent and permanent labeling. This approach is narrowly related to the catalyzed reporter deposition (CARD) technique based on tyramine conjugates and the recently described catalytic cross-linking approach of hydroxystyryl derivatives. The substitution patterns for optimal cross-linking capability and the spectral properties of obtained specific reaction products were studied using an iterative semi-empirical approach. The best staining performance is achieved with N,N-dimethylaminoaryl derivatives. Their N,N-dialkyl homologues as well as the primary aryl amine pendants failed as PO substrates. Due to their basic character, novel substrates occasionally tend to unspecific interactions (staining nuclei, mast cells, or keratin). Centering this side specificity and repressing the staining capability of PO was achieved by chemical modification of the respective dye leading to new specific probes for keratin and cytoplasmatic RNA. In conclusion, catalytic cross-linking of heterocyclic 4-N,N-dimethylamino-styryl dyes represents a promising approach for the permanent fluorescent staining of PO in fixed cells and tissues, complementing the CARD technique. In contrast to CARD-related approaches, new substrates are characterized by a broad excitation and emission range of fluorescence and the outstanding spatial resolution of specific fluorescence signaling known so far from their 4-hydroxystyryl analogues. They currently represent the smallest fluorescent substrates of PO. Histochemical and immuno-histochemical applications share several outstanding features: High detection sensitivity, spatial resolution of fluorescence signaling, and photo stability. 4-N,N-dimethylamino-styryl substrates are compatible with their phenol and phenol-ester analogues. Their combination facilitates the trichromatic immuno-histochemical demonstration of three different targets simultaneously at one excitation wavelength in a conventional epi-fluorescence microscope.

2-Aryl benzimidazoles featuring alkyl-linked pendant alcohols and amines as inhibitors of checkpoint kinase Chk2

A series of benzimidazole compounds containing pendant alcohol and amine moieties was found to be active against checkpoint kinase Chk2. These compounds were prepared to examine a potential hydrogen bond interaction with an active site residue and to investigate replacement of a biaryl linker with an aliphatic system in an effort to improve solubility.

New macrocyclic Schiff-base complexes incorporating a phenanthroline unit. Part 2: Template synthesis of some manganese(II) complexes and crystal structure studies

A series of Mn(II) macrocyclic Schiff-base complexes [MnL n ] 2+ have been prepared via the Mn(II) templated [1+1] cyclocondensation of 2,9-dicarboxaldehyde-1,10-phenanthroline with appropriate linear and branched amines. In this way ligands the pentaaza macrocycle L 1 which is 15-membered and L 2 which is 16-membered possessing no pendant arm, L 6 is 15-membered with one 2-aminoethyl pendant arm and L 8 which is 18-membered hexaaza macrocycle with two 2-aminoethyl pendant arms are formed. All the complexes have been characterized using spectroscopic methods. The crystal structures of [MnL 8](ClO 4) 2 · EtOH were determined and indicate that in the solid state the complex adopts a slightly distorted hexagonal bipyramid geometry with the Mn(II) ion located within a hexaaza macrocycle with the two pendant amines coordinating in the axial positions.

Syntheses and Reactions of Iron(II) Complexes Containing Diphosphine Ligands with Pendant Nitrogen Bases

A series of new iron(II)−hydride complexes that contain diphosphine ligands with pendant amine bases of the formula cis-[HFeL(PNP)2]+, where PNP = Et2PCH2NMeCH2PEt2 and L = CH3CN (3), CO (4), P(OEt)3 (5), have been synthesized and characterized. Protonations of the pendant bases in the PNP complexes have been characterized, and for selected complexes, pKa values have been determined. The acidity of the PNHP ligand depends significantly on the electronic properties of the Fe center to which it is bound, ranging from <7.0 to 12.7, depending on the nature of the coligands present. Unlike the previously studied hydride complexes [HNi(PNP)2]+ and trans-[HFe(CH3CN)(PNP)(dmpm)]+ (where dmpm is bis(dimethylphosphino)methane), the new hydride complexes reported here do not show rapid intramolecular exchange between the protonated base of the diphosphine and the hydride ligand. This is attributed to steric interactions between ethyl substituents on the PNP ligands.