Synthesis,Swelling and Drug-Release Behaviour of a Poly(N,N-diethylacrylamide-co-(2-dimethylamino) ethyl methacrylate) Hydrogel

In this study, poly(N,N-diethylacrylamide-co-(2-dimethylamino) ethyl methacrylate) (poly(DEA-co-DMAEMA)) hydrogels were synthesized by changing the initial DEA/DMAEMA mol ratio. The hydrogels were characterized by Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). In comparison with the PDEA hydrogel, the equilibrium swelling ratio (ESR) and lower critical solution temperature (LCST) of the hydrogels increase with the increase of DMAEMA content in the feed. The deswelling and reswelling kinetics and cytotoxicity of the different composition ratios of DEA to DMAEMA in the co-polymerized hydrogels were also investigated in detail. The absorption and release behaviour of the model drug, bovine serum albumin, were found to be dependent on hydrogel composition and environment temperature, which suggests that these materials have potential application as intelligent drug carriers.     

Polymeric phospholipid analogues, 20. Synthesis and polymerization of 20-(methacryloyloxy)icosyl 2-(trimethylammonio)ethyl phosphate and 32-(methacryloyloxy)dotriacontyl 2-(trimethylammonio)ethyl phosphate

20-(Methacryloyloxy)icosyl 2-(trimethylammonio)ethyl phosphate ( 4a ) and 32-(methacryloyloxy)dotriacontyl 2-(trimethylammonio)ethyl phosphate ( 4b ) were prepared and characterized. These monomers were polymerized and the properties of the resultant polymers are described.     

Synthesis and polymerization of 2-(p-methacryloyloxybenzoyl)ethyl 2′-(phthalimido)ethyl hydrogen phosphate

Benzyl 2-(p-methacryloyloxybenzoyl)ethyl 2′-(phthalimido)ethyl phosphate ( 3 ) and 2-(p-methacryloyloxybenzoyl)ethyl 2′-(phthalimido)ethyl hydrogen phosphate ( 6 ) were prepared, characterized, and polymerized with 2,2′-azoisobutyronitrile (AIBN). The properties of the resultant polymers are described.     

Polymeric insecticides, 2. Synthesis and bioevaluation of polymeric controlled release systems with covalently bound N2-(4-chloro-2-methylphenyl)-N1,N1-dimethylformamidine (chlordimeform) analogues

Polymerizable N²-(4-chloro-2-methylphenyl)-N¹-methylformamidine derivatives of (N-demethyl-chlordimeform) ( 2 ) were prepared, bearing either 4-vinylbenzyloxy- or 2-methacryloyloxyethoxycarbamoyl groups ( 5 and 7 ), and in addition, a triazatriphosphorine derivartive of 2 ( 8 ). The carbamoyl groups and the P-N linkages in the monomers, respectively, were specifically designed to release the insecticide 2 under the particular microenvironmental conditions on cotton leaves by hydrolytic cleaveage, triggered by the pH 8–10 of the leaf surface. Biossaying experiments using larvae of the Egyptian Cotton Leafworm (Spodoptera littoralis) on cotton plants confirmed methacrylate 7 as the only compound with sufficient bioactivity. Corresponding homo- and copolymers of 7 , containing covalently bound pendent moieties of 2 , showed advantageous physiochemical properties with regard to improved efficiency and reduced environmental and handling risks in conventional foliar applications. The biological data suggest that the release rates of the active agent from the polymers vary significantly, depending on the hydrophilicity of the comonomers and the type of formulation used.     

Polymeric phospholipid analogues, 19. Synthesis and polymerization of 10-(11-methacryloyloxyundecyloxycarbonyl)decyl 2-(trimethylammonio)ethyl phosphate

10-(11-Methacryloyloxyundecyloxycarbonyl)decyl 2-(trimethylammonio)ethyl phosphate was prepared, characterized, and polymerized with 2,2′-azoisobutyronitrile (AIBN). The polymer exhibits liquid crystalline behaviour from room temperature up to ca. 280°C and is soluble in methanol and hot ethanol.     

Copolymers of N-vinyl-2-pyrrolidone and 2-(dimethylamino)ethyl methacrylate, 1. Synthesis,characterization, quaternization

2-(Dimethylamino)ethyl methacrylate (DMAEM) — N-vinyl-2-pyrrolidone (VP) copolymers were synthesized and characterized. The copolymerization parameters were determined: r_VP = 0,61, r_DMAEM = 11,41. The tacticity of DMAEM sequences and the distribution of monomer units were estimated. Then, the experimental conditions for the quaternization of the copolymers with alkyl bromides were defined. The modified copolymers were characterized and the mechanism of the quaternization reaction was studied via potentiometry.     

Synthesis and polymerization of benzyl 2-(methacryloyloxy)ethyl hydrogen phosphate

The preparation and characterization of benzyl 2-(methacryloyloxy)ethyl hydrogen phosphate ( 8 ) are described. This monomer was polymerized in the presence of 2,2′-azoisobutyronitrile (AIBN) to give poly{1-[2-(benzylhydrogenphosphato)ethyloxycarbonyl]-ethylene}, ( 9 ), whose properties are also described.     

Synthesis and characterization of photoconductive polymers, 1. Synthesis of poly[2-(9-carbazolyl)ethyl vinyl ether], poly[2-(9-carbazolyl)ethyl 1-propenyl ether], and their various copolymers with ethyl vinyl ether

2-(9-Carbazolyl)ethyl vinyl ether ( 1 ), a known vinyl monomer, was synthesized using a phasetransfer catalyst, and homopolymerized with BF₃OEt₂ or EtAlCl₂.2-(9-Carbazolyl)ethyl 1-propenyl ether ( 2 ) was synthesized by transetherification of ethyl 1-propenyl ether with 9-(2-hydroxyethyl)carbazole in a yield of 34% as a mixture of 49% cis and 51% trans isomer. It was homopolymerized in 90% yield with EtAlCl₂ in toluene at ?25°C. Copolymerization of 1 or 2 with ethyl vinyl ether ( 3 ) were initiated with BF₃OEt₂ or EtAlCl₂. The yields of copolymers were 78–93%, depending on the polymerization conditions. The solubility of both homo- and copolymers was found to be poor. The glass transition temperatures of poly( 1 -co- 3 ) and poly( 2 -co- 3 ) are much lower, than those of poly( 1 ) and poly( 2 ).     

Polymeric phospholipid analogs, 11. Synthesis and polymerization of 2-aminoethyl 2-(p-methacryloyloxybenzoyloxy)ethyl hydrogen phosphate

The preparation and characterization of 2-aminoethyl 2-(p-methacryloyloxybenzoyloxy)ethyl hydrogen phosphate (7) are described. This monomer was polymerized with 2,2′-azoisobutyronitrile (AIBN) and the properties of the resultant polymer are described.     

Protection and polymerization of functional monomers, 14. Anionic living polymerization of 4-[N,N-bis(trimethylsilyl)-aminomethyl]styrene and 4-{2-[N,N-bis(trimethylsilyl)amino]ethyl}styrene

Anionic polymerization of 4-[N,N-bis(trimethylsilyl)aminomethyl]styrene ( 1 ) and 4-{2-[N,N-bis(trimethylsilyl)amino]ethyl}styrene ( 2 ) were carried out at ?78°C in tetrahydrofuran (THF)/pentane mixtures with butyllithium, oligo(α-methylstyryl)lithium, oligo(α-methylstyryl)potassium, and cumylpotassium. Polymerizations of 1 and 2 proceed without chain transfer and termination reactions to give stable “living polymers” when butyllithium or oligo(α-methylstyryl)lithium are used as initiator. The resulting polymers have predictable molecular weights and narrow molecular weight distributions (ratio of weight- to number-average molecular weights, M?_w/M?_n = 1,04–1,14). Under mild acidic conditions (pH 3–5 in THF/water), cleavage of the N? Si bonds in the polymers is completely achieved to give well-defined poly(4-aminomethyl)styrene and poly[4-(2-aminoethyl)styrene]. The triblock copolymers of polystyrene-block-poly( 1 )-block-polystyrene and polystyrene-block-poly( 2 )-block-polystyrene are readily prepared in quantitative yields by sequential polymerization of styrene with living poly( 1 ) or living poly( 2 ).     

Synthesis and characterization of N-isopropyl, N-methacryloxyethyl methacrylamide as a possible dental resin

In this study, N-isopropyl, N-methacryloxyethyl methacrylamide (NIMM) is proposed as a possible reactive diluent in place of triethylene glycol dimethacrylate (TEGDMA) for dental resin mixtures. Real-time infrared spectroscopy was used to monitor the double-bond conversion as a function of irradiation time, and mixtures of 50/50wt% bis-GMA/NIMM were found to reach final conversions (95%) that were 1.5 times greater than bis-GMA/TEGDMA (65%) under visible light irradiation. In addition, samples cured to these conversions were tested with dynamic mechanical analysis. The bis-GMA/NIMM mixture (100% converted) was found to have a higher glass transition temperature and modulus at body temperature than a comparable bis-GMA/TEGDMA mixture (60% converted). Finally, the water sorption and solubility of bis-GMA/NIMM were determined to be higher than the bisGMA/TEGDMA comparison, but the values were still within the range of the ISO 9000s standard. These results suggest that bis-GMA/NIMM mixtures are a viable alternative to conventional dental resins since a greater degree of monomer conversion is obtainable without sacrificing physical and mechanical properties.     

The effect of lodoxamide ethyl[diethyl N,N′-(2-chloro-5-cyano-m-phenylene)dioxamate] on in vivo anaphylactic reactions

Orally administered lodoxamide ethyl (U-42,718) inhibited anaphylactic reactions in a dose-related manner in the following test animals: (1) In the rat PCA reaction, excellent activity (75% inhibition at 0.1 mg/kg) was seen with a duration of activity of 30 min, (2) In the ascaris-sensitive primate (45% inhibition at 1.0 mg/kg) in lung parameters related to increased resistance and decreased compliance which persisted for up to 3 h, and (3) 50 mg/kg protected guinea pigs, sensitized to egg albumin, from lung function changes. Activity in these animal systems indicates that this orally active drug may hold promise in clinical asthma.     

Rate constants for elementary reactions of the radical polymerization of methyl 2-(benzyloxymethyl)acrylate as polymerizable acrylate bearing large substitutents

Methyl 2-(benzyloxymethyl)acrylate (MBZMA) which was synthesized by reaction of methyl 2-(bromomethyl)acrylate with benzyl alcohol was radically homo- and copolymerized. MBZMA polymerized as fast as methyl methacrylate despite of the presence of a large 2-substituent. The absolute rate constants for propagation and termination were evaluated from the direct determination of the steady state concentration of the propagating radical by electron spin resonance spectroscopy at 60°C: k_p = 182 dm³ · mol^?1 · s^?1 and k_t = 1,6 · 10⁶ dm³ · mol^?1 · s^?1. It was deduced from the magnitude of the rate constants that the balance of the slow propagation and termination allows the formation of a polymer. Evaluation of the cross-propagation rate constants in the copolymerization with styrene revealed that primarily the steric effect of the benzyloxymethyl group reduced the reactivity of the polymer radical and that the electronwithdrawing character of the 2-substituent prevailing the steric effect enhanced the monomer reactivity toward the polystyrene radical.     

4-[Diphenyl(trimethylsilyl)methyl]benzophenone as initiator in the photopolymerization of methyl methacrylate and styrene

The polymerization of methyl methacrylate (MMA) and styrene (St) has been studied using 4-[diphenyl(trimethylsilyl)methyl]benzophenone 1 as photoinitiator. The polymerization follows a free radical mechanism; the polymerization rate increases linearly with the monomer concentration and was found to be proportional to the 0.33 and 1.40 power of the photoinitiator and the monomer (MMA) concentration, respectively. The overall activation energy in the case of MMA photopolymerization was calculated to be 25.0 kJ/mol. From ¹H NMR studies it is concluded that the obtained polymers contain two different trimethylsilyl moieties, one at the head and the other at the tail of the polymer chain, showing primary termination reactions even at low initiator concentrations. The p-benzoyltrityl radical 1^· is incorporated into the polymer chain to a very small extent, acting as a scavenger. This is also concluded by laser flash photolysis (LFP) and ESR spectroscopy measurements. A “living” character of the polymerization was observed only at very low initiator concentrations. The triplet state (³ 1 ^*) of the initiator was quenched by styrene, reducing its efficiency. The rate constant k_q of the quenching process of ³ 1 ^* was measured by LFP (k_q = 3.1 · 10⁹ M⁻¹ · S⁻¹). The triplet state and the photodissociation efficiency of the initiator is unaffected by MMA at various concentrations.     

Synthesis and characterization of poly(1-benzoylthiosemicarbazide) and poly(1,3,4-thiadiazole amine) from 2-(p-aminophenyl)-1,3,4-oxadiazoline-5-thione via ring-opening process

A novel thermally stable and semiconducting polyheterocycle, poly(1,3,4-thiadiazole amine), was synthesized from 2-(p-aminophenyl)-1,3,4-oxadiazoline-5-thione via ring-opening. The polymer is a new class of ordered alternating copoly(aniline) containing 1,3,4-thiadiazole heterocyclic units. An investigation of the reaction of 2-phenyl-1,3,4-oxadiazoline-5-thione with aniline was conducted as a model reaction for the polymerization, and poly(phosphoric acid) (PPA) and phosphorus pentoxide/methanesulfonic acid (PPMA) were found to be favorable both as condensing agent and solvent for the formation of 2-anilino-5-phenyl-1,3,4-thiadiazole as a model compound. The polymerization was carried out both by two-step procedure that included ring-opening self-polyaddition giving poly(1-benzoylthiosemicarbazide), followed by cyclodehydration to poly(1,3,4-thiadiazole amine), and by a one-step procedure including cyclodehydration in situ. The poly(1-benzoylthiosemicarbazide) which was formed in the first step in m-cresol had reduced viscosities up to 0,42 dL·g^?1, and it was converted to poly(1,3,4-thiadiazole amine) by treating in PPA or PPMA. Poly(1,3,4-thiadiazole amine) having reduced viscosities up to 0,25 dL·g^?1 was also synthesized by the direct one-step polymerization in PPA or PPMA. The polymer is highly thermally stable and exhibited no weight loss up to 350°C under nitrogen. Its electric conductivity was less than 10^?10 S·cm^?1 at ambient temperature, but markedly increased to 2,9·10^?7 S·cm^?1 upon doping with iodine.     

The cyclo-copolymerization of diallyl compounds and sulfur dioxide, 4. 4-(4-pyridyl)-1,6-heptadiene hydrochloride and sulfur dioxide

Copolymers of 4-(4-pyridyl)-1,6-heptadiene hydrochloride ( 1 ) and 4-(1-buten-4-yl)pyridine hydrochloride ( 2 ) with sulfur dioxide were prepared and their properties were investigated. The effects of the copolymerization conditions on the yields and viscosities of the obtained copolymers were studied. Their structures were studied by elemental analyses, IR, and ¹H- and ¹³C-NMR spectroscopy.     

Polyimidines, 7. Synthesis and the polymerization of 3-(p-Aminophenyl)-3-phenylphthalide

A new monomer for the preparation for polyimidines has been synthesized from 3,3-diphenylphthalide. The starting material can be mononitrated on one of the pendant phenyl groups by the use of acetyl nitrate or nitronium tetrafluoroborate. The resulting nitrophthalide is then reduced to the amine with hydrogen over PtO₂ or with ammonium sulfide with overall yields of 85–90%. 3-(p-Aminophenyl)-3-phenylphthalide then can undergo self-condensation to provide a new polyimidine with a rigid backbone structure which may be a candidate for liquid crystal formation. The condensation can take place at temperatures of 180–350°C, either in polyphosphoric acid or nitrobenzene as solvents, or without solvent in a sealed tube. The yield from the polymerization is as high as 89% and inherent viscosities range up to 0,19 dl/g. Thermal stabilities in air and nitrogen are as high as 520 and 565°C, respectively; however a significant difference occurs in thermal stability for different methods of synthesis. All polymers were soluble in chloroform, dimethylformamide and other organic solvents.     

Synthesis,characterisation and antitumour activity of platinum(II) complexes of novel functionalised poly(amido amine)s

Polyamidoamine polymers were prepared by hydrogen-transfer polyaddition of 2-methylpiperazine to 2,2′-bis(acrylamido)acetic acid sodium salt to yield PAA-1, polyaddition of amino-β-cyclodextrin and 2-methylpiperazine to 2,2′-bis(acrylamido)acetic acid to give PAA-2 and polyaddition of the same amino-β-cyclodextrin and 2-methylpiperazine to 1,4-bis(acryloyl)piperazine to produce PAA-3. These polymers were reacted with cisplatin to give products containing between 8–70 wt.-% platinum. The amount of platinum released from the conjugates during incubation at pH 5.5 and pH 7.4 varied between 0–20%/72 h. PAA-3-Pt showed pH-dependent platinum release. The PAA-platinates were generally less toxic towards lung tumour cell lines in vitro. The IC₅₀ for cisplatin being 2–5 μg/mL and for the PAA-platinates 1–130 μg/mL, this was only to be expected due to their very different cellular pharmacokinetics. In vivo experiments showed that the PAA-1-Pt and PAA-2-Pt were equi-active compared with cisplatin against an i.p. L1210 leukaemia model, confirming their ability to liberate biologically active platinum species. Whereas PAA-1-Pt was significantly less toxic than cisplatin, PAA-2-Pt did show toxicity on repeated dosing, suggesting further investigations are needed to establish the biocompatibility of PAAs containing pendant β-cyclodextrin. PAA-1-Pt is suitable for further in vivo preclinical study in a range of solid tumour models.     

Amino acid based bioanalogous polymers. Synthesis of novel poly(urethane amide)s based on N,N′-(trimethylenedioxydicarbonyl)bis(phenylalanine)

The feasibility of synthesizing high-molecular-weight amino acid based bioanalogous polymers (AABBPs)-poly(urethane amide)s (PUA) — via polycondensation (PC) of di-p-nitrophenyl ester of N,N′-(trimethylenedioxydicarbonyl)bis(L-phenylalanine) ( 3 ) with diamines or their derivatives under mild conditions in organic solvents was studied for the first time. A regular PUA (η_red = 1,53 dL/g) was obtained by PC of 3 with hexamethylenediamine. A dipeptide (Phe-Phe) containing regular poly(ester urethane amide) (η_red = 0,58 dL/g) was synthesized by PC of 3 with p-toluenesulfonic acid salt of bis(L-phenylalanine) 1,4-butylene diester. A tripeptide (Phe-Lys-Phe) containing PUA (η_red = 0,38 dL/g) with pendent ester groups was prepared via PC of 3 with N,N-bis(trimethylsilyl)-L-lysine methyl ester. These novel AABBPs which may be considered as structural analogs of AB type bioanalogous polymers — conventional poly(amino acids) are of interest in enzymology, immunology, pharmacology, and biotechnology (as materials for biomedical applications).