Betaine Units Research Articles

Immobilization and Release Studies of Triazole Derivatives from Grafted Copolymer Based on Gellan-Carrying Betaine Units.

New polymer-bioactive compound systems were obtained by immobilization of triazole derivatives onto grafted copolymers and grafted copolymers carrying betaine units based on gellan and N-vinylimidazole. For preparation of bioactive compound, two new types of heterocyclic thio-derivatives with different substituents were combined in a single molecule to increase the selectivity of the biological action. The 5-aryl-amino-1,3,4 thiadiazole and 5-mercapto-1,2,4-triazole derivatives, each containing 2-mercapto-benzoxazole nucleus, were prepared by an intramolecular cyclization of thiosemicarbazides-1,4 disubstituted in acidic and basic medium. The structures of the new bioactive compounds were confirmed by elemental and spectral analysis (FT-IR and 1H-NMR). The antimicrobial activity of 1,3,4 thiadiazoles and 1,2,4 triazoles was tested on gram-positive and gram-negative bacteria. The triazole compound was chosen to be immobilized onto polymeric particles by adsorption. The Langmuir, Freundlich, and Dubinin–Radushkevich adsorption isotherm were used to describe the adsorption equilibrium. Also, the pseudo-first and pseudo-second models were used to elucidate the adsorption mechanism of triazole onto grafted copolymer based on N-vinylimidazole and gellan (PG copolymer) and grafted copolymers carrying betaine units (PGB1 copolymer). In vitro release studies have shown that the release mechanism of triazole from PG and PGB1 copolymers is characteristic of an anomalous transport mechanism.

New Grafted Copolymers Carrying Betaine Units Based on Gellan and N-Vinylimidazole as Precursors for Design of Drug Delivery Systems.

New grafted copolymers possessing structural units of 1-vinyl-3-(1-carboxymethyl) imidazolium betaine were obtained by graft copolymerization of N-vinylimidazole onto gellan gum followed by the polymer-analogous reactions on grafted polymer with the highest grafting percentage using sodium chloroacetate as the betainization agent. The grafted copolymers were prepared using ammonium persulfate/N,N,N′,N′ tetramethylethylenediamine in a nitrogen atmosphere. The grafting reaction conditions were optimized by changing one of the following reaction parameters: initiator concentration, monomer concentration, polymer concentration, reaction time or temperature, while the other parameters remained constant. The highest grafting yield was obtained under the following reaction conditions: ci = 0.08 mol/L, cm = 0.8 mol/L, cp = 8 g/L, tr = 4 h and T = 50 °C. The kinetics of the graft copolymerization of N-vinylimidazole onto gellan was discussed and a suitable reaction mechanism was proposed. The evidence of the grafting reaction was confirmed through FTIR spectroscopy, X-ray diffraction, 1H-NMR spectroscopy and scanning electron microscopy. The grafted copolymer with betaine structure was obtained by a nucleophilic substitution reaction where the betainization agent was sodium chloroacetate. Preliminary results prove the ability of the grafted copolymers to bind amphoteric drugs (cefotaxime) and, therefore, the possibility of developing the new sustained drug release systems.

Physicochemical and biological properties of polyampholytes: Quaternized derivatives of poly(4-vinylpyridine)

The modification of poly(4-vinylpyridine) with ω-bromocarboxylic acids and alkyl bromides yields three types of polyampholytes: polyampholytes containing both cationic and anionic groups in each monomer unit (polybetaines), polyampholytes containing betaine and cationic units, and polyampholytes containing betaine units and side cetyl radicals. Their complex formation with liposomes formed from zwitterionic (electroneutral) phosphatidylcholine and anionic diphosphatidylglycerol (cardiolipin) is investigated. The method for fixation of polymers on the liposomal membrane and the stability of the formed complexes are determined by the chemical structure of macromolecules. For the most part, polyelectrolytes are electrostatically adsorbed on the membrane and are fully removed from it with an increase in the salt concentration in the surrounding solution. An exception is the polybetaine obtained through the modification of poly(4-vinylpyridine) with ω-bromobutyric acid, which irreversibly binds to liposomes probably owing to the incorporation of macromolecular fragments into the hydrophobic part of the lipid bilayer. The insertion of side cetyl radicals into polybetaine molecules stabilizes their complexes with liposomes in the presence of salts. The cytotoxicity of the synthesized polyampholytes is one to two orders of magnitude lower than that of a cationic polymer with the same degree of polymerization.

Short and symmetrical OHO hydrogen bond in bis(quinuclidine betaine) hydrochloride

The molecular structure of bis(quinuclidine betaine) hydrochloride, (QNB) 2HCl, has been characterized by single crystal X-ray diffraction, infrared spectroscopy and by DFT calculations. The crystals are centrosymmetric, monoclinic, space group C2/c. Two QNB moieties are joined by a very short and centered O⋯H⋯O hydrogen bond of 2.461(2) Å. Its existence is confirmed by the broad absorption band below 1500 cm −1 in the FTIR spectrum. In the structure of (QNB) 2HCl optimized at the B3LYP/6-31G(d,p) level of theory, the quinuclidine betaine units are non-equivalent. The protonated quinuclidine betaine interacts with the QNB inner salt by the O H⋯O hydrogen bond of 2.494 Å. In the structure of (QNB) 2H homoconjugated cation, optimized by the B3LYP/6-31G(d,p) approach, the OHO bond is shorter than in the crystal (2.415 Å). A study of the motion of the proton along the O H⋯O bridge has been carried out by the semiempirical PM3 method.

Contributions to the photochemistry of poly(4-vinylpyridine) and its ionic derivatives in the presence of water

Films of poly(4-vinylpyridine), poly(N-carboxyethyl-4-vinylpyridine) and poly(N-allyl-4-vinylpyridine) chloride were exposed at a radiation spreading between about 250 and 270 nm, and the photochemical processes were monitored by spectroscopic methods. Reaction mechanisms considering: (i) a double role of the water molecule, to form water–pyridine ring hydrogen bonds and to accept hydrogen atoms, (ii) the scission of C H methine bonds in units with photoexcited pyridine rings, (iii) the scission of N + C bonds in betaine units, and (iv) crosslinks appearing by recombination of carbon macroradicals or by the addition of methine groups to allyl groups, were found to explain the photocrosslinking of the three polymers. Their properties of crosslinking photoresists were observed by AFM and the best ones were found for the polymer with N-allyl-pyridinium chloride units.

Conformational richness and multiple Z′ in salt co-crystal of N-methylpiperidine betaine with N-methylpiperidine betaine hexafluorosilicate

The co-crystal structure of N-methylpiperidine betaine with N-methylpiperidine betaine hexafluorosilicate represents an unusual case of a salt co-crystal with a high Z' value (3), unexpected conformational variability, and with nearly 50% of its contents disordered. The betaine units from the salt and co-crystal formers are paired into several homoconjugated dimers via very short, linear O(-)...H(+)...O(-) bridges. These hydrogen bonds are the dominating interactions in the co-crystal structure, in variance with the simple hexafluorosilicate salt, which has a structure governed by COOH...F hydrogen bonds. The SiF(2-)(6) anion in the co-crystal structure has only C-H...F interactions with the betaine units. The zwitterion:cation:anion stoichiometry is 3:3:1.5. Some of the betaine units display disorder, but each case is different. One of the SiF(2-)(6) anions is ordered while possessing exact crystallographic symmetry. The other one is disordered in a general position. In addition, there are three water molecules in the crystal structure. One is fully ordered, one has an H atom disordered in two positions and the third one occupies two alternative positions with unequal populations.

The influence of halide anions on the molecular structure of bis( N-methylpiperidine betaine) monocation with short hydrogen bond

The crystal structure of the 2:1 (basic) salt of N-methylpiperidine betaine (zwitterionic molecule) with hydrochloric acid (MPB) 2H·Cl, reveals that the N-methylpiperidine betaine units are hemiprotonated and form a dimeric cation through a short O·H·O hydrogen bond of 2.446(2) Å. The piperidine ring has a chair conformation with the methyl group in the axial and the –CH 2COO substituent in the equatorial position. The Me–N +–CH 2–COO unit has a gauche conformation. The investigated complex is isomorphous with (MPB) 2H·Br and pseudo-isomorphous with (MPB) 2H·I. The short hydrogen bond is described by a symmetrical double-minimum potential. The halide anions form weak C–H⋯X − hydrogen bonds with the N +–CH 2 and N +–CH 3 groups. A linear relation exists between the C–H⋯X − distance and the halide ionic radius. Eight conformers of the [(MPB) 2H] + cation and three conformers of the anion formed by (1-methyl-cyclohexyl)acetate units, [(MCHA) 2H] −, were analyzed by the B3LYP/6-31G(d,p) level of theory in order to investigate the effect of the N +⋯O electrostatic interactions on the conformation of MPB and on the short O·H·O hydrogen bond. The effect of the counter-ions on the FTIR and NMR spectra of the (MBP) 2H·X complexes is also discussed.

Synthesis and properties of fluoroalkyl end‐capped sulfobetaine polymers

AbstractA variety of fluoroalkyl end‐capped 3‐[N‐(3‐acrylamido)propyl‐N,N‐dimethylammonio]propanesulfonate polymers [RF–(APDAPS)n–RF] were prepared by the reactions of fluoroalkanoyl peroxides with the corresponding monomer under very mild conditions. Similarly, fluoroalkyl end‐capped 2‐vinylpyridinio propane sulfonate polymer was obtained by the use of fluoroalkanoyl peroxide. These fluoroalkyl end‐capped sulfobetaine polymers exhibited a good solubility in water; however, these polymers have a poor solubility in other solvents. In particular, RF–(APDAPS)n–RF polymers caused gelation in methanol, although RF–(VPPA)n–RF polymer showed no gelation in methanol. RF–(APDAPS)n–RF polymers were found to form the self‐assembled molecular aggregates with the aggregations of the end‐capped fluoroalkyl segments and the ionic interactions between sulfobetaine segments in aqueous solutions. On the other hand, it was suggested that RF–2‐vinylpyridinio propane sulfonate (VPPS)n–RF polymer is not likely to form the self‐assemblies in aqueous solutions because of the steric hindrance of pyridiniopropyl betaine units in polymer. We also studied the surfactant properties of RF–(APDAPS)n–RF and RF–(VPPS)n–RF polymers compared with those of other fluoroalkyl end‐capped betaine‐type polymers such as 2‐acrylamido‐2‐methylpropanesulfonic acid polymers and 2‐(3‐acrylamidopropyldimethylammonio) ethanoate polymers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 1144–1153, 2004

Crystal and molecular structure of bis( N-methylpiperidine betaine) hydroiodide

The crystal structure of 2:1 complex of N-methylpiperidine betaine with hydroiodic acid, (MPB) 2HI, reveals that the betaine units are hemiprotonated and form a dimeric cation through a short and symmetric O⋯H⋯O hydrogen bond (R(O⋯O)=2.447(1) Å). The piperidinium ring has a chair conformation with the methyl substituent in the axial and the carboxymethyl substituent in the equatorial position. The conformation of the betaine frame is identical as in the analogous (MPB) 2HBr, even though the acidic proton is attached to the opposite carboxylate O atom. This remarkable difference can be viewed as a 180° rotation of the –COO·H group or as a proton jump. The framework of the I −/H + centers is largely unchanged but the betaine units swivel around the H + sites to bring the alternate carboxylate O atoms into the O⋯H⋯O bridge, resulting in a pseudo-isomorphous relation between these two crystals. In its altered environment, the I − anion rests in an enlarged hydrophobic cavity where it accepts a number of more regularly arranged C–H⋯I hydrogen bonds. Two conformers ( I and II) of the [(MPB) 2H] + cation were analyzed by the B3LYP/6-31G(d,p) level of theory. In I the N + atom is closer to the O⋯H group, while in II it is closer to the CO group. The calculated O⋯O distances are shorter than in the crystal. FTIR spectrum of (MPB) 2HI shows a broad and intense νOHO absorption in the 1500–400 cm −1 range, which is similar to that of type A acid salts of carboxylic acids and other 2:1 betaine complexes with mineral acids.

Application of the Kauffmann Areno-Analogy Principle − Stability towards Oxidation of the Methylene Spacers in Quadrupolar [14]Heterophane Frameworks Incorporating 4- or 3-Pyridiniomethyl-1,2,4-triazolate Betaine Units

Incorporation of 3,5-bis-3(4)-pyridiniomethyl-1,2,4-triazolate units into the structures of novel bis-betaines in [14](meta-para)2heterophane systems has shown that the structural features conferred by the heterophane framework result in macrocycles that, in contrast to their building blocks, are stable towards oxidation. The stability of [14]metaheterophanes is consistent with their betaine subunits.

Synthesis, modelling and characterisation of novel non-linear optical polymer containing indandionylpyridinium betaine units

In the present article we report about the synthesis, quantum chemical model calculations and non-linear optical characterisation of a novel polyurethane based polymer — a bipolar organic compound N-(indan-1,3-dion-2-yl)-4- N′, N′-dialkyaminopyridinium betaine (IPB) containing charged electron donor and electron acceptor groups covalently bonded to polyurethane polymer backbone. This newly synthesised IPB containing polymer can be regarded as a promising thermally stable organic non-linear optical material with a long time performance for photonics applications.

A new class of second-order non-linear optical material: stilbazolium benzimidazolate covalently bound to polymer backbone

This paper describes the first example of the preparation of stilbazolium benzimidazolate covalently bound to polymer backbone using a novel methacrylate monomer, 2-{4-[2-(4-methacryloyloxyphenyl)ethenyl]pyridinio}benzimidazolate. A free radical copolymerization of 2-{4-[2-(4-methacryloyloxyphenyl)ethenyl]pyridinio}benzimidazolate (1 equiv.) with butyl methacrylate (6 equiv.) provided a methacrylate polymer containing 1.7 mol% of betaine units. The resulting polymer exhibited a glass transition temperature of 30 °C. The number-average (M n ) and weight-average (M w ) molecular masses were 36 900 and 79 300, respectively, estimated by GPC measurement. The second-order non-linear optical property of the obtained polymer was investigated by second-harmonic generation (SHG) measurements applying the Maker fringe method using a Q-switched Nd:YAG laser (1064 nm) as an exciting beam after corona-poling, indicating that the d 33 value of the resulting copolymer was 5.1 pm V -1 .

Non-classical [14]metaheterophanes containing betaine units. Synthesis, NMR spectroscopy and X-ray crystallography

The N-diphenylmethyl derivative 4 is the immediate precursor of the N-substituted dipolar [14]metaheterophane 3, and allows the convenient synthesis of the unsubstituted macrocycle 5, which can be transformed into the quadrupolar or dipolar heterophanes 1 and 2; the molecular structures of 1 and 2 were confirmed by single-crystal X-ray analysis.