Microporous hypercrosslinked polystyrene sorbents with the degrees of crosslinking of 100, 150, and 200

In this study, hypercrosslinked copolymers (HCCPs) designated as HCCP-1DVB, HCCP-2DVB and HCCP-3DVB were obtained by post-crosslinking of styrene-divinylbenzene copolymers with the various molar content of divinylbenzene (1, 2, and 3%) using chloromethyl methyl ether via the Friedel-Crafts reaction. The chemical structure, porous and morphological characteristics of hypercrosslinked copolymers were determined by FT-IR, low-temperature nitrogen adsorption-desorption method and SEM, respectively. The synthesized hypercrosslinked copolymers had high surface area values and different micro/mesoporous structures. It was found that mesopore volume increased with a decrease in divinylbenzene content in a copolymer. HCCP-1DVB had the largest mesopore volume (0.53 cm 3 /g), the highest adsorption capacity for rifampicin ( q m = 183.27 mg/g), and the highest rifampicin adsorption rate. Adsorption capacity of HCCP-1DVB towards rifampicin is comparable with other adsorbents used for its adsorption or even significantly higher. The adsorption equilibrium and kinetic processes were well described by the Langmuir model and the pseudo-second-order model. The experimental data indicated that the removal efficiency of rifampicin reached 99.8% at the dosage of HCCP-1DVB equal to 80 mg/10 mL. The removal efficiency of rifampicin by HCCP-1DVB was higher than by some tested commercial hypercrosslinked adsorbents. After 5 cycles of reuse, the adsorption capacity of HCCP-1DVB decreased only by 7%, which indicates sufficient stability and reusability of this hypercrosslinked copolymer.

Water-soluble complexes of N-vinylpyrrolidone/N-vinylamine copolymers with lactones of D-glucuronic acid were obtained and characterized by chromatographic, spectral, and hydrodynamic methods. The complexes efficiently inhibited the enzyme β-glucuronidase that causes the appearance of bladder tumors. The products demonstrated prolonged action and were stable during storage.

N-vinylpyrrolidone-co-allylamine copolymers (VP-co-AA) containing iminodiacetic (IDA) chelation units were prepared in the range of molecular masses of the copolymers from 9000 to 30,000 Da depending on polymerization conditions. Non-radioactive organometallic species Re(CO)3+ were introduced into polymeric carriers under mild conditions; the prepared metal–polymeric complexes were characterized by IR, NMR, ESI-MS and HPLC. IR spectra data confirmed the coordination of M(CO)3+ moiety to the polymeric backbone via IDA chelation unit (appearance of characteristic fac-M(CO)3+ vibrations (2005, 1890 cm−1), as well as the appearance of group of signals in 1H NMR spectra, corresponding to those inequivalent to methylene protons CH2COO (dd, 4.2 ppm), coordinated to metal ions. The optimal conditions for labeling the PVP-co-AA-IDA copolymers with radioactive 99mTc(CO)3+ species were determined. The radiochemical yields reached 97%. The obtained radiolabeled polymers were stable in blood serum for 3 h. In vivo distribution experiments in intact animals showed the high primary accumulation of technetium-99m MPC (MM = 15,000 Da) in blood with subsequent excretion via the urinary tract.

Dithiocarbamate (DTC) derivatives of N-vinylpyrrolidone-N-vinylamine (VP–VA) copolymers were synthesized via reaction between the copolymers and carbon disulfide in alkaline medium; molecular masses of the products were 12 and 29 kDa; the VP:VDTC ratios were 94:6 and 83:17 mol.%. Complexation between the obtained DTC derivatives and metal ions (indium and gallium) was investigated. It was demonstrated that metal–DTC ligand complexes with 1:3 ratio between components were formed. Gallium metal–polymer complexes (MPC) were unstable in solution. Individual indium MPC were isolated and characterized by spectral and chromatographic methods. Unlike similar gallium MPC, they appeared to be stable in histidine challenge reaction.

Синтезировали сополимер с молекулярной массой 45 кДа, содержаний 7 мол.% звеньев виниламина, 80 мол.% винилпирролидона и 3 мол.% звеньев винилиминодиуксусной кислоты. Методом высокоэффективной эксклюзионной жидкостной хроматографии исследовали его комплексообразование с ионом Ga 3+ . Дана характеристика металл-полимерного комплекса методами эксклюзионной хроматографии и спектральными методами (ИК, 1 Н ЯМР). Комплекс имел мономолекулярную структуру, где ион металла играл роль анкерного фрагмента между звеньями винилиминодиуксусной кислоты и был стабилен в реакции интерлигандного обмена с гистидином.

A terpolymer with a molecular weight of 45 kDa containing 7 mol % of vinylamine units, 80 mol % of vinylpyrrolidone, and 3 mol % of vinyliminodiacetic acid units has been synthesized. Its complexation with Ga3+ ion has been studied by HPLC. The resulting metal–polymer complex has been characterized by exclusion chromatography and spectral (IR, 1H NMR) data. The complex has a monomolecular structure where the metal ion acts as an anchor fragment between vinyliminodiacetic acid units and is stable in the reaction of interligand exchange with histidine.

The method for preparation of copolymers of N-vinylpyrrolidone (VP) and N-vinylamine (VA) with high yield were developed; the method involves radical copolymerization of VP with N-vinylformamide(VFA) followed by the removal of formyl protecting group in the presence of inorganic acids. The optimal conditions for synthesis of copolymers with predefined compositions and molecular masses were determined. The influence of temperature, concentrations of reactants, and the nature of an acid on the rate of formyl group removal was estimated. Spectral and chromatographic methods of analytical control of the contents of residual monomers and formic acid (which forms during acidic hydrolysis of the copolymer) were developed.

Terpolymers with a molecular weight of 65 and 13 kDa containing 90 mol.% of N-vinylpyrrolidone, 7 mol.% of N-vinylformamide, and 3 mol.% of N-vinyliminodiacetic acid units have been synthesized. Diethyldithiocarbamate and benzyldithiocarbamate have been used as coligands. The mixed-ligand complexation with Ga3+ ion has been studied by HPLC. The composition and structure of the resulting metal-polymer complexes have been determined by exclusion chromatography and spectral (IR, 1H NMR) data.

Синтезировали тройные сополимеры с молекулярной массой 65 и 13 кДа и содержанием N‑винилпирролидона (90 мол.%), N‑винилформамида (7 мол.%) и 3 мол.% N‑винилиминодиуксусной кислоты. В качестве дитиокарбаматных колигандов использовали диэтилдитиокарбамат и безилдитиокарбамат. Методом ВЭЖХ исследовали реакцию смешанно-лигандного комплексообразования с ионом галлия. Состав и структуру металл-полимерных комплексов определили с помощью эксклюзионной хроматографии и спектральных методов (УФ-, ИК- и 1 Н ЯМР‑спектроскопия).

Chromatographic methods of analysis of the products of the radical copolymerization of random copolymers of N-vinyl-2-pyrrolidone and 6-crotonoyl aminohexanoic acid are developed and molecular characteristics of the copolymers are determined. A method is proposed for the purification of the obtained carboxylated water-soluble copolymers of monomeric hydrophobic acid impurities by low-pressure gel-permeation chromatography.

Mixed-ligand metal-polymer complexes (MPC) of N-vinylpyrrolidone-N-vinylformamide-N-vinyl iminodiacedic acid (VP-VFA-VIDA) copolymers and diethyldithiocarbamate (DEDTC) as a co-ligand with indium were synthesized under mild conditions and pH close to physiological values. Isolated MPC were characterized by UV, IR, H-1 NMR, atomic absorption spectrophotometry, and HPLC. The obtained data implied that the MPC contain 8-10wt% of (IDA)In(DEDTC) fragments. The optimal conditions for radiochemical synthesis of VP-VFA-VIDA-In-111-(DEDTC) metal-polymer complex with mixed ligands were defined. The closest coordination environment of In-111 was studied by perturbed angular correlation technique. The obtained data are in good agreement with the information about weight amounts of the corresponding indium MPC.

The method for analysis of transition metal ions (Zn(II), Cu(II), Со(II), Ni(II), Fe(III)) by high-performance planar (thin layer) chromatography with the use of sorbents modified by chelating fragments of iminodiacetic acid was developed. The correlation between retention factor (Rf) and physico-chemical parameters of the separated systems was studied. It was demonstrated that unlike the pH value, ionic strength of a solution does not exert significant influence on resolution and mobility of transition metal cations

Complexation between perrhenate ion and N-methyl-N-vinylacetamide and N-methyl-N-vinylamine copolymers in aqueous solutions was studied by high-performance liquid chromatography on monolith ultrashort columns. It was demonstrated that complexation has slow kinetics and strongly depends on the length of alkyl substituent.

Synthetic methods for random copolymers of N-vinylpyrrolidone and 6-crotonoyl aminohexanoic acid (6-CAHA) were developed. These carboxyl-containing water-soluble copolymers are the promising drug carriers. The technique for purification of polymers of this type from admixed comonomer (hydrophobic 6-CAHA) was proposed. Molecular masses, sizes, and molecular mass distributions were determined by HPLC, optical and hydrodynamic methods.

The exclusion mechanism of the separation of poly(N-vinylformamide) and its derivatives with a cysteamine terminal group in gel permeation chromatography implemented by the suppression of polyelectrolyte swelling and the electroexclusion of macromolecules was established by the transport analytical methods of molecular hydrodynamics (HPLC, velocity sedimentation, and intrinsic viscosity). Based on an analysis of the hydrodynamic characteristics and molecular weights of polymer fractions determined by velocity sedimentation, it was found that the molecular characteristics and polydispersity of the water-soluble poly(N-vinylamide) s of aliphatic carboxylic acids and their derivatives can be calculated with the use of the Benoit universal calibration dependence.

The procedure of the directed synthesis of N-vinylpyrrolidone-N-vinylformamide (VP-VFA) copolymers with grafted iminodiacetate (IDA) chelating units is presented. The methods for labelling resulting conjugates with indium-113m were developed. The metal-copolymer conjugates were characterized by different physicochemical methods, including IR and NMR, viscometry, light scattering, and exclusion high-performance liquid chromatography. Parameters of radiochemical synthesis of the conjugates labelled with indium-113m were optimized. It was shown that the VP-VFA-IDA copolymer firmly binds indium-113m both in the acid and alkaline solutions, with pH of the reaction mixture having almost no effect on the complexation. VP-VFA-IDA-In conjugates were found to be unstable in histidine challenge reaction.