Andrey Shlyakhtin

We present an in-depth analysis of Raman spectra of novel block copolymers of methyl ethylene phosphate (MeOEP) with caprolactone (CL) and L-lactide (LA), recorded with the excitation wavelengths of 532 and 785 nm. The experimental peak positions, relative intensities and profiles of the poly(methyl ethylene phosphate) (PMeOEP), polycaprolactone (PCL) and poly(L-lactide) (PLA) bands in the spectra of the copolymers and in the spectra of the PMeOEP, PCL and PLA homopolymers turn out to be very similar. This clearly indicates the similarity between the conformational and phase compositions of PMeOEP, PCL and PLA parts in molecules of the copolymers and in the PMeOEP, PCL and PLA homopolymers. Experimental ratios of the peak intensities of PMeOEP bands at 737 and 2963 cm⁻¹ and the PCL bands at 1109, 1724 and 2918 cm⁻¹ can be used for the estimation of the PCL—b—PMeOEP copolymers chemical composition. Even though only one sample of the PMeOEP—b—PLA copolymers was experimentally studied in this work, we assume that the ratios of the peak intensities of PLA bands at 402, 874 and 1768 cm⁻¹ and the PMeOEP band at 737 cm⁻¹ can be used to characterize the copolymer chemical composition.

Composite biocompatible scaffolds, obtained using the electrospinning (ES) technique, are highly promising for biomedical application thanks to their high surface area, porosity, adjustable fiber diameter, and permeability. However, the combination of synthetic biodegradable (such as poly(ε-caprolactone) PCL) and natural (such as gelatin Gt) polymers is complicated by the problem of low compatibility of the components. Previously, this problem was solved by PCL grafting and/or Gt cross-linking after ES molding. In the present study, composite fibrous scaffolds consisting of PCL and Gt were fabricated by the electrospinning (ES) method using non-functionalized PCL1 or NHS-functionalized PCL2 and hexafluoroisopropanol as a solvent. To provide covalent binding between PCL2 and Gt macromolecules, NHS-functionalized methyl glutarate was synthesized and studied in model reactions with components of spinning solution. It was found that selective formation of amide bonds, which provide complete covalent bonding of Gt in PCL/Gt composite, requires the presence of weak acid. With the use of the optimized ES method, fibrous mats with different PCL/Gt ratios were prepared. The sample morphology (SEM), hydrolytic resistance (FT-IR), cell adhesion and viability (MTT assay), cell penetration (fluorescent microscopy), and mechanical characteristics of the samples were studied. PCL2-based films with a Gt content of 20 wt% have demonstrated the best set of properties.

Aliphatic polyesters are an important class of polymeric materials for biomedical applications due to their versatile and tunable chemistry, biocompatibility and biodegradability. A capability of direct bonding with biomedically significant molecules, provided by the presence of the reactive end functional groups (FGs), is highly desirable for prospective polymers. Among FGs, N-hydroxysuccinimidyl activated ester group (NHS) and maleimide fragment (MI) provide efficient covalent bonding with –NH– and –SH containing compounds. In our study, we found that NHS- and MI-derived acyl chlorides efficiently terminate living ring-opening polymerization of ε-caprolactone, L-lactide, ethyl ethylene phosphonate and ethyl ethylene phosphate, catalyzed by 2,6-di-tert-butyl-4-methylphenoxy magnesium complex, with a formation of NHS- and MI-functionalized polymers at a high yields. Reactivity of these polymers towards amine- and thiol-containing model substrates in organic and aqueous media was also studied.

The control of surface bioadhesive properties of the subcutaneous implants is essential for the development of biosensors and controlled drug release devices. Poly(alkyl ethylene phosphate)-based (co)polymers are structurally versatile, biocompatible and biodegradable, and may be regarded as an alternative to poly(ethylene glycol) (PEG) copolymers in the creation of antiadhesive materials. The present work reports the synthesis of block copolymers of ε-caprolactone (εCL) and 2-ethoxy-1,3,2-dioxaphospholane-2-oxide (ethyl ethylene phosphate, EtOEP) with different content of EtOEP fragments, preparation of polymer films, and the results of the study of the impact of EtOEP/εCL ratio on the hydrophilicity (contact angle of wetting), hydrolytic stability, cytotoxicity, protein and cell adhesion, and cell proliferation using umbilical cord multipotent stem cells. It was found that the increase of EtOEP/εCL ratio results in increase of hydrophilicity of the polymer films with lowering of the protein and cell adhesion. MTT cytotoxicity test showed no significant deviations in toxicity of poly(εCL) and poly(εCL)-b-poly(EtOEP)-based films. The influence of the length of poly(EtOEP)chain in block-copolymers on fibrotic reactions was analyzed using subcutaneous implantation experiments (Wistar line rats), the increase of the width of the fibrous capsule correlated with higher EtOEP/εCL ratio. However, the copolymer-based film with highest content of polyphosphate had been subjected to faster degradation with a formation of developed contact surface of poly(εCL). The rate of the degradation of polyphosphate in vivo was significantly higher than the rate of the degradation of polyphosphate in vitro, which only confirms an objective value of in vivo experiments in the development of polymer materials for biomedical applications.

There is a current clinical need for the development of bone void fillers and bioactive bone graft substitutes. The use of mesenchymal stem cells (MSCs) that are seeded into 3D scaffolds and induce bone generation in the event of MSCs osteogenic differentiation is highly promising. Since calcium ions and phosphates promote the osteogenic differentiation of MSCs, the use of the calcium complexes of phosphate-containing polymers is highly prospective in the development of osteogenic scaffolds. Calcium poly(ethylene phosphate)s (PEP-Ca) appear to be potentially suitable candidates primarily because of PEP’s biodegradability. In a series of experiments with human adipose-tissue-derived multipotent mesenchymal stem cells (ADSCs), we demonstrated that PEP-Ca are non-toxic and give rise to osteogenesis gene marker, bone morphogenetic protein 2 (BMP-2) and mineralization of the intercellular matrix. Owing to the synthetic availability of poly(ethylene phosphoric acid) block copolymers, these results hold out the possibility for the development of promising new polymer composites for orthopaedic and maxillofacial surgery.

Catalytic ring-opening polymerization (ROP) of cyclic esters (lactides, lactones) and cyclic ethylene phosphates is an effective way to process materials with regulated hydrophilicity and controlled biodegradability. Random copolymers of cyclic monomers of different chemical nature are highly attractive due to their high variability of characteristics. Aryloxy-alkoxy complexes of non-toxic metals such as derivatives of 2,6-di-tert-butyl-4-methylphenoxy magnesium (BHT-Mg) complexes are effective coordination catalysts for homopolymerization of all types of traditional ROP monomers. In the present paper, we report the results of density functional theory (DFT) modeling of BHT-Mg-catalyzed copolymerization for lactone/lactide, lactone/ethylene phosphate and lactide/ethylene phosphate mixtures. ε-Caprolactone (ε-CL), l-lactide (l-LA) and methyl ethylene phosphate (MeOEP) were used as examples of monomers in DFT simulations by the Gaussian-09 program package with the B3PW91/DGTZVP basis set. Both binuclear and mononuclear reaction mechanistic concepts have been applied for the calculations of the reaction profiles. The results of calculations predict the possibility of the formation of random copolymers based on l-LA/MeOEP, and substantial hindrance of copolymerization for ε-CL/l-LA and ε-CL/MeOEP pairs. From the mechanistic point of view, the formation of highly stable five-membered chelate by the products of l-LA ring-opening and high donor properties of phosphates are the key factors that rule the reactions. The results of DFT modeling have been confirmed by copolymerization experiments.

Poly(ethylene phosphates) are promising polymers for use in biomedical applications. Catalytic ring-opening polymerization (ROP) of cyclic ethylene phosphate monomers (CEPMs) is the most effective approach for obtaining these polymers. The mechanism of coordination ROP of CEPMs remains unclear. We report, for the first time, the results of DFT modeling of CEPM ROP. In these calculations by Gaussian-09 program package with the B3PW91/DGTZVP basis set, we explored methyl ethylene phosphate (MeOEP) ROP catalyzed by dimeric and monomeric catalytic species derived from heteroleptic complex [(BHT)Mg(μ-OBn)(THF)]₂ (Mg1, BHT = 2,6-di-tert-butyl-4-methylphenolate). Analysis of the reaction profiles for the binuclear and mononuclear reaction mechanisms allowed us to conclude that the ROP of MeOEP is preferentially catalyzed by mononuclear Mg complexes. This estimation was confirmed by comparative polymerization experiments using MeOEP and traditional monomers ε-caprolactone (εCL), racemic lactide (rac-LA), and l-lactide (l-LA) initiated by Mg1. ROP of MeOEP proceeds at an extremely high rate due to the substantially lower activation barrier calculated for mononuclear mechanism in comparison with that of cyclic esters that polymerize without the dissociation of BHT-Mg binuclear species. We also demonstrated the use of MeOEP as a "monomerization" agent in the synthesis of MeOEP-lactide block copolymers. Comparison of the multiple acceleration of l-LA ROP after MeOEP prepolymerization and formation of atactic PLA blocks in rac-LA polymerization with the heterotactic PLA formation during Mg1-catalyzed homopolymerization also confirmed the mononuclear nature of the polyphosphate-containing catalytic particles.

The title compound, {Al[O-2,6-(Ph₂CH)₂-4- ^t BuC₆H₂]Et₂(THF)} or [Al(C₂H₅)₂(C₃₆H₃₃O)(C₄H₈O)], was formed in the reaction between 4-tert-butyl-2,6-bis(diphenylmethyl)phenol and triethylaluminum in the presence of THF (THF is tetrahydrofuran) and recrystallized from hexane. The structure has monoclinic (P2₁/n) symmetry with a single Al atom in the asymmetric unit. The terminal C atom of one ethyl substituent is nearly equally disordered over two positions. The complex possesses catalytic activity in the ring-opening polymerization of ∊-caprolactone.

Ternary copolymers of acrylonitrile with methylacrylate, itaconic acid (IA), and its derivatives, namely, monomethyl ester (MME), monoethyl ester (MEE), monoamide, and mono-n-octylamide, were synthesized in a supercritical carbon dioxide medium. The morphology of the synthesized copolymers was studied by scanning electron microscopy. Copolymers with IA, MME, and MEE were obtained in the form of regularly shaped particles of nearly 1 μm in size without the addition of stabilizers.

Nd, La and Y triphosphates were prepared via the reaction of potassium ionol ethyl phosphate with the corresponding lanthanide nitrates or chlorides in water. According to the X-ray diffraction data, the recrystallised reaction products were dimers. The products did not contain water, were readily soluble in hydrocarbon solvents and demonstrated promising catalytic properties in the polymerisation of butadiene and DL-dilactide.