Free COOH Groups Research Articles

Crosslinking ofXNBRlatex with multifunctional epoxides: An energy‐efficient curing strategy for the fabrication of accelerator‐free rubber gloves

AbstractHerein, we pursue an efficient curing strategy using multifunctional epoxides, which undergo a nucleophilic ring opening reaction across the free COOH groups of a carboxylated nitrile butadiene rubber (XNBR). Following a prevulcanization protocol, we cure the rubber in the latex phase at 60°C. Thin films are then prepared by using a conventional coagulant dipping process, in which the final cure degree of the elastomer is reached during drying (postvulcanization). In a comprehensive approach, cure kinetics, tensile properties, and crosslink density of the thin elastomer films are studied as a function of the functionality and concentration of the applied crosslinker. The results clearly show that films with high tensile strength (39 MPa) are obtained without prevulcanization. Stability tests reveal that the shelf life of the latex formulations is limited to less than 1 day due to hydrolysis reactions of the epoxy groups of the water‐soluble crosslinker. However, the storage stability can be extended to several days if nonwater‐soluble epoxy crosslinkers are applied. The decent shelf life together with the fast cure rates and excellent mechanical properties make epoxy crosslinking a promising curing strategy for preparing dipped rubber gloves without hyperallergenic accelerators used in classical sulfur vulcanization.

Lanthanides adsorption on metal-organic framework: Experimental insight and spectroscopic evidence

Herein, lanthanides (Samarium: Sm, Lanthanum: La, and Erbium: Er) adsorption mechanism over copper trimesate metal-organic framework (Cu-BTC MOF) was studied. The MOF crystallized as [Cu(HBTC)(H2O)3] and [Cu3(BTC)2] with a rod-like structure and abundant free COOH groups. The Langmuir adsorption capacity of 1007.1, 656.5, and 410.5 mg g−1 was recorded for Sm, La, and Er, respectively. The adsorption process was driven by rapid ion exchange with crystal structure transformation in the first hour of mixing, mediated by the surface ion-exchange phenomenon and free COOH groups. After 1 h, the process was driven by a slow ion-exchange mechanism where Ln ions drifted internally, and Cu ions moved out towards the surface. Among the three lanthanides studied, Er/Cu-BTC system was more sensitive to structural reorganization with the increasing Ln/Cu ratio. The work reported here is one of the first detailed accounts of the Ln-adsorption process in MOFs.

Antiviral activity of glycyrrhizic acid conjugates with amino acid esters against Zika virus

Zika virus (ZIKV) is a new pathogenic flavivirus transmitted by mosquitoes Aedes spp. ZIKV infection is accompanied by serious neurological complications and is especially dangerous for pregnant women, in which it can lead to congenital malformations of the fetus and microcephaly in neonates. Currently, there are no licensed vaccines or specific post-infectious therapies for ZIKV infection. This report is devoted to the study of glycyrrhizic acid (GL) derivatives as ZIKV inhibitors. The inhibitory assays on the cytopathic effect (CPE) and viral infectivity of ZIKV in three different human cell lines revealed that the conjugation of GL with amino acids and their esters (methyl, ethyl) is influenced by the antiviral activity of the compounds. GL conjugates with Glu(OMe)-OMe 11, Glu(OH)-OMe 12, Asp(OMe)-OMe 13, TyrOMe 14, LeuOEt 15, and PheOEt 16 with free COOH groups in the triterpene moiety were active against ZIKV. The most active compounds 13 and 14 have IC50 values of 0.23 μM and 0.09 μM against low doses (MOI = 0.05) of ZIKV strain PRVABC59, 1.20 μM and 0.74 μM against high doses (MOI = 10) of ZIKV strain Natal RGN single-round infectious particles, respectively. The lead compound was 14 with a high selectivity index (SI < 500). Compound 13 showed a higher inhibitory effect on the early stage (entry) of ZIKV replication than compound 14, and was less potent than compound 14 at the post-entry stage, consistent with the docking models. Compounds 13 and 14 also had a strong interaction with the active site pocket of NS5 MTase. Compounds 13 and 14 are recommended for expanded antiviral studies against ZIKV infection.

In silico guided designing of 4-(1H-benzo[d]imidazol-2-yl)phenol-based mutual-prodrugs of NSAIDs: synthesis and biological evaluation

ABSTRACT The free COOH group of conventional NSAIDs is a structural feature for non-selective cyclooxygenase (COX) inhibition and the molecular cause of their gastrointestinal (GI) toxicity. In this context, an in house database of synthesizable ester prodrugs of some well-known NSAIDs was developed by combining their -COOH group with -OH of a newly identified antioxidant 4-(1H-benzo[d]imidazol-2-yl)phenol (BZ). The antioxidant potential of BZ was unveiled through in silico PASS prediction and in vitro/in vivo evaluation. The in house database of NSAIDs-BZ prodrugs was first subjected to screening with our previously reported pharmacophore models of hCES1 (AAHRR.430) and hCES2 (AHHR.21) for determining hydrolytic susceptibility. Biotransformation behaviour of screened prodrugs was then assessed by using QM/MM and sterimol parameterization, followed by ADMET calculations to predict the drug likeness. On the basis of in silico results, five prodrugs were duly synthesized and the best three were subject to the in vivo evaluation for their anti-inflammatory, analgesic, antioxidant activities, and ulcerogenic index. Among these prodrugs, BN2 and BN5 displayed better anti-inflammatory and analgesics potential in comparison to their parent drugs. All the prodrugs were found to be gastro sparing in the rat model and significantly improved the levels of oxidative stress biomarkers in both blood plasma as well as gastric homogenate.

Brønsted-Lewis dual acid sites in a chromium-based metal-organic framework for cooperative catalysis: Highly efficient synthesis of quinazolin-(4H)-1-one derivatives

A novel MIL-101(Cr) (MIL, Matérial Institut Lavoisier) supported propyl carboxylic acid, denoted here as MIL-101(Cr)-NH-CO-Pr-COOH, has been fabricated by post-synthetic modifications of nitro-functionalized MIL-101(Cr), MIL-101(Cr)-NO2. The resulting MOF was successfully characterized by using FT-IR, XRD, N2 adsorption-desorption, 1H NMR, SEM, ICP-OES, elemental analysis and TGA. Then, the prepared solid was used as an extremely highly effective multifunctional catalyst for the one-pot three-component synthesis of quinazolin-4(1H)-one derivatives as biologically active nitrogen heterocyclic compounds under solvent-free conditions. The important features of this methodology are good to excellent yields of products, the use of very small amounts of catalyst, short reaction time, non-requirement of organic solvents, and environmental benign and mild reaction conditions. Furthermore, turnover frequency was found to be in the range 3.5–50 h−1 under neat conditions, which is comparable to the reported previously for this reaction. Significantly, compared with the pristine MOF and the related homogenous catalysts, the MIL-10 1(Cr)-NHCO-Pr-COOH exhibited superior catalytic activity which can be attributed to the synergistic effect between isolated Lewis acidic Cr(III) nodes and Brønsted acidic free COOH groups in addition to the cooperative interplay of the Brønsted acid and the amine sites within the framework. More remarkably, MOF was stable and reusable up to three times without any changes in its activity and structure.

Electrochemical biosensor for the detection of hydrogen peroxide using cytochrome c covalently immobilized on carboxyl functionalized ionic liquid/multiwalled carbon nanotube hybrid

Owing to the importance of hydrogen peroxide (H2O2) in environment and biological systems, selective and sensitive detection of this key analyte has gained a large interest in the area of electroanalytical chemistry. Herein, we have synthesized highly water-insoluble phosphonium based carboxyl functionalized ionic liquid (TPP-HA[TFSI]) and characterized using various spectral techniques and single crystal X-ray diffraction. The synthesized TPP-HA[TFSI] was deposited over a multiwalled carbon nanotube (MWCNT) coated glassy carbon electrode (GCE). Thus obtained TPP-HA[TFSI]/MWCNT/GCE was used as a host matrix for the covalent immobilization of water soluble protein cytochrome c (Cyt c) through EDC/NHS coupling reaction to form a stable amide bond between free COOH groups of TPP-HA[TFSI] and -NH2 groups of Cyt c (Cyt c/TPP-HA[TFSI]/MWCNT/GCE). Electrochemical characterization of the fabricated electrode by cyclic voltammetry revealed distinct redox peaks corresponding to the heme active sites of Cyt c (FeIII/FeII) with a cathodic and anodic peak at −0.39 V and −0.27 V. Further, the modified electrode exhibited excellent performance towards electrochemical reduction of H2O2. A stable catalytic response was observed at an operating potential of −0.45 V using amperometry. The linear range, sensitivity and detection limit for the determination of H2O2 at Cyt c/TPP-HA[TFSI]/MWCNT/GCE were found to be 20 to 892 μM, 0.14 μA μM−1 cm−2 and 6.2 μM, respectively. Notably, the proposed modified electrode demonstrated excellent selectivity and sensitivity towards the determination of H2O2 along with remarkable stability and reproducibility.

Proton-Conductive Keggin-Type Clusters Decorated by the Complex Moieties of Cu(II) 2,2′-Bipyridine-4,4′-dicarboxylate/Diethyl Analogues

Three proton-conductive decorated Keggin-type clusters, {[Cu(debpdc)(H2O)3][Cu(debpdc)(H2O)Cl][PMo12O40]} ·2CH3OH ·1.5CH3CN ·3H2O (1), {[Cu(H2bpdc)(H2O)2Cl0.5]2[PW12O40]}·10H2O (2), and {[Cu(H2bpdc)(H2O)2.5]2[SiW12O40]}·10H2O (3) (where debpdc is diethyl 2,2'-bipyridine-4,4'-dicarboxylate and H2bpdc is 2,2'-bipyridine-4,4'-dicarboxylic acid), were synthesized through electrostatic and coordination interactions between Keggin-type anions and Cu(II) H2bpdc/debpdc complex moieties. Interestingly, in the three complexes, both the H2bpdc/debpdc and the Keggin anion are covalently linked to the Cu2+ ions as polydentate organic and inorganic ligands, respectively. Notably, complexes 2 and 3 are the first examples of the functionalization of a Keggin-type cluster with Cu(II)-H2bpdc complex moieties, thereby providing a pathway to design and synthesize multifunctional hybrid materials with cluster structures based on two building units. In them, the free COOH groups of the H2bpdc ligand can act as both hydrogen bond acceptors and proton carriers. 1 has debpdc ligands with ethoxycarbonyl groups, while 2 and 3 have the H2bpdc ligands with free COOH groups; thus, the three complexes help us to understand the influence of the different substituents on the proton conductivity. The measurement results reveal that 2 and 3 have a high conductivity value of over 10-3 S cm-1 at 100 °C under 98% relative humidity, which is 2 orders of magnitude higher than that of 1 under the same conditions.

Insight into the interaction between hydrogen bonds in brown coal and water

The hydrogen bonds between water and oxygen-containing functional groups are key factors controlling water re-adsorption and drying behaviour of brown coal. However, the changes of hydrogen bonds are hard to investigate because of the overlap of H2O IR vibration bands with those due to coal hydrogen bonds. Thus, D2O was innovationally used instead of H2O to interact with brown coal. The interaction between re-adsorbed water and the hydrogen bonds of brown coal was investigated by studying the IR spectra changes and the release of D2O, HDO, H2O and CO2 during drying of brown coals containing adsorbed D2O. The Gibbs free energies of reactions involving hydrogen bonds were calculated to complement the findings of IR measurements. The effect of re-adsorbed water on hydrogen bonds of brown coal and the interaction among them during drying process were revealed for the first time. The results show that the OH–π and COOH dimer hydrogen bonds in dried brown coal are easily disrupted by re-adsorbed water. During the brown coal drying process, the re-adsorbed water cannot be completely removed, but some of it participates in the rearrangement of hydrogen bonds. The remaining re-adsorbed water is hydrogen-bonded to the free OH and free COOH groups at higher temperature. The free OH groups are obtained from the decomposition of cyclic OH tetramer and OH–ether hydrogen bonds, and the free COOH groups from the disruption of COOH dimer disrupted by re-adsorbed water. The self-associated n-mers (n > 3) and OH–N hydrogen bonds are formed during the brown coal drying process. The infrared peak positions of COD bonds formed by D2O molecules bonded to free OH groups and free COOH groups are found to be 2575 and 2490 cm−1, respectively. Some O–D bonds remain intact at temperatures as high as 330 °C. Thus in situ DRIFT spectrum analysis combined with isotopic substitution provides a rapid and direct method for research on water behaviour in brown coal.

Pathway Diversity Leads to 2D-Nanostructure in Photo-triggered Supramolecular Assembly.

This Communication reports photo-triggered supramolecular assembly of a naphthalene-diimide (NDI) derivative, appended with a photo-labile ortho-nitrobenzyl (ONB)-ester protected carboxylic acid. Photo-irradiation produces the free COOH group which facilitates H-bonding-driven face-to-face stacking of the NDI chromophores producing an ultra-thin (height <2.0 nm) two-dimensional (2D) nanosheet. In contrast, spontaneous supramolecular assembly of the same active monomer exhibits entirely different features such as uncontrolled growth, J-aggregation and fibrillar morphology. A completely different pathway for photo-triggered assembly is attributed to the dual function of the photo-caged pro-monomer in i) producing the carboxylic acid in controlled manner and ii) simultaneously inhibiting the spontaneous J-aggregation of the photo-generated monomers by ester-carboxylic acid H-bonding and in turn directing a distinct growth mechanism.

An Uncommon Carboxyl-Decorated Metal-Organic Framework with Selective Gas Adsorption and Catalytic Conversion of CO2.

A new three-dimensional (3D) framework, [Ni(btzip)(H2 btzip)]⋅2 DMF⋅2 H2 O (1) (H2 btzip=4,6-bis(triazol-1-yl)isophthalic acid) as an acidic heterogeneous catalyst was constructed by the reaction of nickel wire and a triazolyl-carboxyl linker. Framework 1 possesses intersected 2D channels decorated by free COOH groups and uncoordinated triazolyl N atoms, leading to not only high CO2 and C2 H6 adsorption capacity but also significant selective capture for CO2 and C2 H6 over CH4 and CO in 273-333 K. Moreover, 1 reveals chemical stability toward water. Grand Canonical Monte Carlo simulations confirmed the multiple CO2 - and C2 H6 -philic sites. As a result of the presence of accessible Brønsted acidic COOH groups in the channels, the activated framework demonstrates highly efficient catalytic activity in the cycloaddition reaction of CO2 with propylene oxide/4-chloromethyl-1,3-dioxolan-2-one/3-butoxy-1,2-epoxypropane into cyclic carbonates.

Chromatographic Release Profile of Active Pharmaceutical Ingredients of Synthesized Prodrug and Codrug of Aspirin+Paracetamol and Indomethacin+Paracetamol in Physiological Fluids

Prodrug is the precursor of drug which is made by derivatization of the same to enhance the bioavailability by pharmacokinetics, lipid solubility by partition coefficient and increase the physicochemical and biochemical parameters by pharmacodynamics. All two prodrugs showed different logP values and molecular weights according to the solubility parameters and electronegativity: logP profile: Prodrug-B>Prodrug-A; molecular weight profile: Prodrug-B>Prodrug-A. The main side effect of NSAID is gastric acidity due to release of free H+ because all NSAIDs have free-COOH (carboxylic acid) group which act by competitive inhibition of cyclooxygenase enzyme (COX1/COX2). Here the target of this project has been designed in such a way to convert the free –COOH/–OH of API (aspirin/paracetamol) into prodrug of two ester (–COO–) and one amide (– CONH–) linkage (Prodrug-A) and one ester and two amide linkage (Prodrug-B) which releases free API after metabolic hydrolysis in acidic pH: 1-4 and alkaline pH: 7-9. Since the prodrugs are repository forms so chances to release gastric acid has been minimized due to non-availability of free-COOH group in stomach. The biotransformation of active drug from prodrug takes such a time in stomach that all goes upto duodenum and then ileum of small intestine that chances of acidity is reduced. Finally all prodrugs go to small intestine where alkaline pH starts so gastric acidity is reduced. Since all two prodrugs are made of two NSAID: Prodrug-A (logP=2.15) releases Aspirin and Paracetamol, Prodrug-B (logP=3.94) releases Indomethacin and Paracetamol which shows distinct two Rt values in HPLC both in acidic an alkaline hydrolysis and these Rt values of Prodrugs match with the individual API components so the purpose of our goal has been completed successfully. The pH of gastric acid varies from 1.5- 3.5 in the human stomach lumen, the acidity being maintained by the proton pump H+/K+ ATPase. So the pattern for acid hydrolysis was adjusted at pH=3- 3.5 by HCl. The pH of intestine varies from 5.6-6.9, so the pattern for alkaline hydrolysis was adjusted at pH=7.0-8.0 by NaOH. In case of codrug which is made by non-covalent interactions such as hydrogen bonding, ionic interactions, Van der Waals interactions and π-interactions between two APIs, so the release of parent molecule will be faster than prodrug both in acidic as well as in alkaline pH because prodrug is made by covalent bonding between two APIs. log P profile: Codrug-B (3.42)>Codrug-A (1.55); molecular weight profile: Codrug-B (508.94g)>Codrug-A (331.31g).

Polyelectrolyte coating on superparamagnetic iron oxide nanoparticles as interface between magnetic core and biorelevant media

Nanoparticles do not exist in thermodynamical equilibrium because of high surface free energy, thus they have only kinetic stability. Spontaneous changes can be delayed by designed surface coating. In biomedical applications, superparamagnetic iron oxide nanoparticles (SPIONs) require an optimized coating in order to fulfil the expectation of medicine regulatory agencies and ultimately that of biocompatibility. In this work, we show the high surface reactivity of naked SPIONs due to ≡Fe-OH sites, which can react with H+/OH- to form pH- and ionic strength-dependent charges. We explain the post-coating of naked SPIONs with organic polyacids via multi-site complex bonds formed spontaneously. The excess polyacids can be removed from the medium. The free COOH groups in coating are prone to react with active biomolecules like proteins. Charging and pH- and salt-dependent behaviour of carboxylated SPIONs were characterized quantitatively. The interrelation between the coating quality and colloidal stability measured under biorelevant conditions is discussed. Our coagulation kinetics results allow us to predict colloidal stability both on storage and in use; however, a simpler method would be required to test SPION preparations. Haemocompatibility tests (smears) support our qualification for good and bad SPION manufacturing; the latter 'promises' fatal outcome in vivo.

ChemInform Abstract: Selective Co/Ti Cooperatively Catalyzed Biaryl Couplings of Aryl Halides with Aryl Metal Reagents.

Various aryl bromides or chlorides, including those bearing a free COOH, OH, CONHR, and SO2NHR group, coupled with aryl magnesium or lithium reagents in the presence of 7.5 mol % CoCl2/15 mol % PBu3 and substoichiometric Ti(OEt)4 (40 mol % to ArM) at room temperature in high yields with high chemo- and regioslectivity. This simple reaction represents the first example of Co/Ti cooperative catalysis which plays a key role in suppressing undesired homocouplings.

Carboxylic group modification as a method of intensification of diuretic properties of 7-hydroxy-5-oxo-2,3-dihydro-1h,5h-pyrido[3,2,1-ij]quinoline-6-carboxylic acid 2-carboxyanilide

The intensive and purposeful search of fundamentally new diuretics conducted by our research laboratory among the derivatives of 4-hydroxyquinolin-2-ones has found 7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij] quinoline-6-carboxylic acid 2-carboxyanilide as an intermediate lead compound. The basis for it is a high diuretic activity and a low toxicity of this substance. However, a free carboxylic group, which is often conductive to appearance of an extremely undesirable ulcerogenic action in relation to the gastro-intestinal tract, can be a serious obstacle for using the given compound as a drug. That is why we attempted to block the carboxylic group of 2-carboxyanilide by one of the known methods. For this purpose the methodology of both classical and non-classical bioisosteric replacements has been used. When conducting the synthetic part of the research the alternative ways of close structural analogues of the basic molecule were considered. As a result the optimal method for their obtaining has been offered; it differs by the minimal time costs and preparative high yields and purity of the target products. The structure of all substituted 7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij] quinoline-6-carboxanilides synthesized has been confirmed by the data of elemental analysis, counter synthesis and NMR 1Н spectra. The primary pharmacological screening in studying the effect of the compounds obtained on the excretory function of the kidneys has been carried out in white outbread rats using the standard method. The testing has been performed in parallel and in comparison with Hydrochlorothiazide, as well as the abovementioned 2-carboxyanilide. It has been determined that some compounds under study in the dose of 10 mg/kg when introduced orally exceed not only Hydrochlorothiazide, but the basic molecule as well. By the results of the experiments carried out the structural and biological regularities that are important for further research have been found. As a new lead compound 7-hydroxy-5-oxo-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxylic acid 2-carbamoylanilide has been suggested. It has no free COOH-group and, therefore, is not capable of having an great effect on the gastro-intestinal tract.

Protein immobilization on nanoporous silicon functionalized by RF activated plasma polymerization of Acrylic Acid

Plasma Enhanced Chemical Vapor Deposition (PECVD) technique is used to polymerize Acrylic Acid for the surface functionalization of porous silicon samples with different pore dimensions. The polymer shows free COOH groups also at the pores inner surface, suitable for the immobilization of fluorescent labeled Protein A. The stability of the polymer, its role in the protection from aging of the porous matrix and the efficiency of the functionalization for the binding of protein A have been characterized by ATR–FTIR, SEM, Optical Contact Angle and Fluorescence Microscopy. The polymerization process is well controllable and suitable for the functionalization of porous silicon leaving free carboxylic groups at the surface ready for the immobilization of biochemical species for sensing applications.

Selective Co/Ti Cooperatively Catalyzed Biaryl Couplings of Aryl Halides with Aryl Metal Reagents

Various aryl bromides or chlorides, including those bearing a free COOH, OH, CONHR, and SO2NHR group, coupled with aryl magnesium or lithium reagents in the presence of 7.5 mol % CoCl2/15 mol % PBu3 and substoichiometric Ti(OEt)4 (40 mol % to ArM) at room temperature in high yields with high chemo- and regioslectivity. This simple reaction represents the first example of Co/Ti cooperative catalysis which plays a key role in suppressing undesired homocouplings.

Assembly of a pcu topological porous Cd-trimesate framework with free carboxylic acid group: Sorption and luminescent property

A six connected 3D porous coordination polymer {[Cd(HBTC)(BPz)]·3EtOH}n (1) (H3BTC = benzene-1,3,5-tricarboxylic acid, BPz = 3,3′,5,5′-tetramethyl-4,4′-bipyrazole) has been synthesized from mild solvothermal reaction of Cd(NO3)2·4H2O with BPz and H3BTC in ethanol. Complex 1 is a thermally stable microporous MOF having (Cd2(COO)2) as the secondary building unit (SBU) with a six connected pcu topology. The pores of the polymer are decorated with free COOH groups which show moderate N2 sorption (38 cc g− 1) at 77 K with a BET surface area of 129 m2 g− 1. Complex 1 also exhibited photoluminescent property in solid state with λmax at 396 nm.

Phototunable Surface Interactions

Photoresponsive polymer brushes constitute an attractive platform for tuning surface properties and functionality. Since the degree of photoconversion can be controlled by the light dose, functional states with intermediate properties between those of the nonexposed and fully exposed brushes are accessible. Here we investigate the light-modulated interfacial, adhesion, and frictional properties of photosensitive polymer brushes with a methacrylate backbone and ionizable -COOH side groups modified with the photoremovable group 6-nitroveratryloxycarbonyl (NVOC). The original brush (PNVOCMA) gradually changes into a charged poly(methacrylic acid) (PMAA) brush upon exposure to ultraviolet light due to the photoremoval of the chromophore and generation of free COOH groups. We show how the physical properties of the brush can be gradually tuned with the exposure dose using condensation microscopy, atomic force microscopy (AFM), force mapping, and friction force spectroscopy.

Modification of hemicelluloses with polycarboxylic acids

Abstract Polycarboxylic acids (PCAs) aroused interest as crosslinking agents for natural polymers, such as cellulose, starch, chitosan, and hemicelluloses (HC), for improving their water resistance and imparting them new properties. Here, PCAs were studied for the crosslinking of HC films. HCs were isolated from gray alder (Alnus incana L.) wood as a water-soluble fraction by sawdust extraction with 7% potassium hydroxide. Citric acid (CA), maleic acid (MA), and butane tetracarboxylic acid (BTCA) served as crosslinking agents in the presence of sodium hypophosphite as a catalyst. The crosslinking reaction was followed by the analysis of free and esterified COOH groups in HC films. At temperatures below 100–110°C, the HC esterification process with BTCA proceeded very slowly. At 140°C, most of the acids’ COOH groups reacted with HC during 1–1.5 h. BTCA had a higher esterification activity than CA and MA. The obtained films retained their form on immersing in water and subsequent drying in the open air. The water retention value of films followed the reaction kinetics, that is, decreased with increasing reaction time. Water-resistant films were obtained with no &lt;10–11% of BTCA and 20% of CA based on the weight of HC. The water vapor sorption capacity of the films after modification with 10% BTCA decreased approximately twice in the whole range of the relative humidity of air compared with the case of unmodified HC films.

PLGAs bearing carboxylated side chains: Novel matrix formers with improved properties for controlled drug delivery

Novel PLGA derivatives bearing carboxylated side chains have been synthesized and used to encapsulate the fragile drug apomorphine HCl with a solid-in-oil-in-water solvent extraction/evaporation method. Blends of d,l-lactide and l-3-(2-Benzyloxycarbonyl)Ethyl-1,4-Dioxane-2,5-dione (BED) were co-polymerized at different ratios via ring-opening using benzyl alcohol as initiator. Optionally, the ester groups in the side chains as well as the terminal ester groups were hydrogenolyzed (leading to free COOH groups). For reasons of comparison, different types of “conventional” PLGAs were also synthesized and used for apomorphine HCl encapsulation. The polymers and microparticles were thoroughly characterized using SEC, 1H NMR, DSC, SEM, X-ray and laser diffraction, Headspace-GC as well as in vitro drug release measurements in flow-through cells and agitated flasks. Importantly, microparticles based on the new polymers bearing carboxylic groups in the polymeric side chains: (i) allowed a significant reduction of the amount of residual solvent (dichloromethane), and (ii) provided different types of drug release patterns compared to microparticles based on “conventional” PLGAs (at least partially due to altered polymer degradation kinetics). Thus, they offer an interesting potential as novel matrix formers in controlled drug delivery systems, overcoming potential shortcomings of standard PLGAs.