Search

This work deals with the problem of synthesis and investigation of the structure and properties of polymer calcium phosphate biopolymer suspensions, their use to obtain film samples containing drugs, and the study of the kinetics of drug release from the polymer matrix. The compositions were synthesized using the method of mechano-acoustic activation. The use of the mechano-acoustic activation technique and ultrasonic dispersion makes it possible to synthesize calcium phosphate compounds in aqueous media, to modify the synthesized products with drugs and bioactive substances, and to form biocompositions for the manufacture of bone implants.

Работа посвящена проблеме синтеза и изучения структуры и свойств полимерных кальций-фосфатных биополимерных суспензий, получению на их основе пленочных образцов с лекарственными веществами и изучению кинетики их высвобождения из полимерной матрицы. Синтез композиций осуществляли с помощью метода механоакустической активации. Применение техники механоакустической активации, ультразвукового диспергирования позволяют проводить синтез кальций-фосфатных соединений в водных средах и модифицировать синтезированные продукты лекарствами, биоактивными веществами и формировать биокомпозиции для изготовления костных имплантатов. Ключевые слова: механоакустическая активация, кальций-фосфатные соединения, биополимерные композиты, гидроксиапатит, порфирины.

Hydroxyapatite was synthesized in conditions of mechanoacoustic treatment of an aqueous reaction mixture consisting of ammonium hydrogen phosphate and calcium nitrate using a commercially available rotary pulsation apparatus. Mechanoacoustic treatment of the reaction mixture was found to lead to the formation of nanosized hydroxyapatite particles with a predominant mean diameter of about 20 nm. Purification of technical hydroxyapatite to remove traces of ammonium nitrate by thermal processing at 350°C is proposed. The crystalline phase of hydroxyapatite was found not to be dominant in the structure. The porosity of hydroxyapatite amounted to about 75% with a mean pore diameter of 2.8 × 103 nm. Thermal processing of hydroxyapatite in aqueous medium was found to yield a paste-like form. Hydroxyapatite paste had no cytotoxicity and did not prevent cell adhesion, though it almost completely inhibited cell spreading.

An organo-mineral composite bone-grafting material was developed and tested. The composite material is based on synthetic hydroxyapatite (HAP) (30-60 wt%) integrated into the matrix of poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel. The composite was shown to have a homogeneous and isotropic microstructure, mechanical strength of ~11 MPa, high degree of water absorption reaching 34%, and elastomeric properties under physio-logical conditions (strain at failure is 57%).

Biotechnology industry is rapidly developing. The elaboration of new biomaterials for bone reconstruction is one of the most perspective directions in tissue engineering. There are millions of surgical operations associated with use of bone graft materials every year. In this article we tried to analyze and systematize data about advanced technologies and modern trends in the preparation of bio-composite bone graft materials. Special attention is given to 3D-prototyping that allows making bone implants with individual form. Introduction of molecular biology technologies such as activating specific cytokines and growth factors at the right time makes it possible to optimize bone regeneration process. The article has also some suggestions on further improvement of the bone engineering technology.Индустрия биотехнологий бурно развивается. Разработка новых биоматериалов для восстановления дефектов костной ткани - одно из самых перспективных направлений тканевой инженерии. Количество хирургических вмешательств, связанных с применением костезамещающих материалов, во всем мире исчисляется миллионами. Мы попытались провести анализ и систематизировать данные, касающиеся современных технологий и трендов в изготовлении биокомпозиционных костезамещающих материалов, а также обобщить первые результаты собственных исследований. Отдельного внимания заслуживают такие методы производства биоматериалов, как объемное или 3D-прототипирование, позволяющее изготавливать костные имплантаты сложной индивидуальной формы. Внедрение технологий молекулярной биологии позволяет контролировать регенерацию кости путем активации специализированных цитокинов и факторов роста в нужные временные этапы. Высказаны предположения о путях дальнейшего совершенствования технологий костной инженерии.

New technological approaches based on biocompatible nanocomposites with hydroxyapatite (HA) and collagen matrix are described. Optimal conditions of HA synthesis in collagen fibers and its use in bone implants are discussed.

An effective route to the oxidation of organic derivatives of trivalent phosphorus with an aqueous solution of hydrogen peroxide was considered. Phenylphosphonites, including those having a hydrolytically unstable phosphorus-nitrogen bond were involved into the oxidation. The identification of oxidation products, the phenylphosphonates, was carried out using the method of ion cyclotron resonance mass spectrometry with Fourier transform combined with electrospray ionization, and by 31P and 1H NMR spectroscopy. The influence of an effective antioxidant of natural origin, quercetin, on the oxidation was demonstrated.

Reactions of phosphorous triamides with symmetrical diols in equimolar ratio were studied. These reactions result in formation of unique poly(oligo)amidophosphorous systems. The products obtained are used as ligands for the synthesis of metal complexes of a new type.

4,4′-Dihydroxybiphenyl was condensed with phenylphosphonous tetraethyldiamide. The moleccular mass, chemical composition, and structural features of the product, oligo(4,4′-biphenylene phenylphosphonite), were elucidated using the method of matrix-activated laser desorption/ionization, with a time-of-flight (TOF) mass analyzer. The oligophenylphosphites containing labile P-N bond, which are unstable under conditions of recording mass spectra, were stabilized by conversion into oligophenylphosphonates. 1H-Tetrazole catalyzes the reaction of phenylphosphonous tetraethyldiamide with 4,4′-dihydroxybiphenyl. Cross-linking in the solid state of the oligo(4,4′-biphenylene phenylphosphonite) containing terminal phosphonamidite group leads to gradual increase in the molecular weight and is accompanied by redox processes.

Condensing phosphorylation of 1,6-hexanediol, 1,4-dihydroxybenzene, 4,4′-dihydroxybiphenyl, and 2,2-bis(4′-hydroxyphenyl)propane by phenylphosphonous acid tetraethylamide was effected by treatment of the disperse reaction system with high-frequency sound. This treatment ensures efficient shift of the phase equilibrium in the course of condensation and increases the yield of phenylphosphonous acid oligoesters.

Step high-temperature condensation of dihydric phenols [1,4-dihydroxybenzene, 4,4′-dihydroxybiphenyl, and 2,2′-bis(4-hydroxyphenyl)propane] with phenylphosphonous bis(diethylamide) is carried out. The molecular weight, composition, and structure of the resulting oligomeric arylene phenylphosphonites were assessed by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The widest mass range was observed in the mass spectrum of 4,4′-dihydroxybiphenyl, which corresponds to an oligomer having about 30 elementary units. The obtained data agree with the the molecular weight measured by high-speed sedimentation. The reactions of phenylphosphonous bis(diethylamide) with dihydric phenols give both acyclic and cyclic arylene phenylphosphonites.

A representative of the new class of organophosphorus ligands, viz., o,o"-dimethylene(tri-p-cresyl) bicyclophosphite (BCP), was studied as a promoter of Rh(acac)(CO)2 in hydrogenation and hydroformylation. BCP enhances the activity and stability of the catalyst much more strongly than analogous organophosphorus ligands used previously (triphenylphosphine, triphenyl phosphite, and etriolphosphite). A reason for this behavior of BCP was studied using NMR spectroscopy, quantum-chemical calculations, and molecular simulation. The high sensitivity of the 1H NMR signals of the methylene groups of BCP toward complexation appears due to the high density of the highest occupied and lowest unoccupied MO of protons of the CH2 groups, especially those directed toward the P atom. The 1H and 31P NMR spectra indicate the formation of hydrides of two types (HRh(BCP)3 and HRh(BCP)4) directly upon the addition of BCP in amounts exceeding that corresponding to the BCP/Rh = 2 ratio to a solution of Rh((acac)(CO)2. The most probable source of the hydride ion is the BCP molecule itself, namely, the bridging CH2 groups. The molecular mechanics simulation showed that in the [Rh(BCP)3]+ complexes the aromatic rings of BCP formed two molecular cavities. These cavities can alternatively open and close, thus providing flexible screening of the catalytic site. This explains the unusual behavior of the Rh complexes with BCP in hydrogenation and hydroformylation.

Quercetin pentaacetate (Qu(OAc)5) was obtained by the acylation of quercetin by method (5) and then reduced with sodium metal in ethanol. The features of the electronic structure of the quercetin pentaacetate reduction product were studied by analyzing the ESR spectra of ketyl resulting from the dissociation of the corresponding pinacolate. Figure 1 shows the ESR spectrum of the sodium ketyl of acetylated quercetin. The calculation of the spin density distribution using the Priroda software allowed us to assign a doublet with а Н = 2 G in the spectrum of quercetin ketyl to the

Interaction between the equimolecular amounts of glycols (diatomic phenols) and phosphorous acid triamides in diglyme or without solvent gives phosphorus-bearing polyamidophosphites. The structure of these compounds was studied by NMR spectroscopy, and it was shown that a partial disproportionation of amidophosphite fragments into phosphite ones can occur in the course of their synthesis. The chemical properties of the obtained compounds are being studied. First rhodium complexes with polyamidophosphite ligands were obtained. These complexes are shown to be more active hydrogenation catalysts than the corresponding low-molecular complexes. 1

Phosphorous triamides react with aliphatic diols and dibasic phenols: 1,6-hexanediol, 2,2'-(4-hydroxyphenyl)propane, 1,4-hydroquinone, and 4,4'-dihydroxybiphenyl in the temperature range 80-110°C in diethylene glycol dimethyl ether or without a solvent to afford phosphorus-containing regular high-molecular products having an O2P(NR2) moiety in the monomeric unit. The resulting poly(phosphoramidites) are capable of swelling in organic solvents, and they can be used as macroligands in the catalytic hydrogenation of styrene over rhodium(I) complexes.

Complexation of Rh(I) with o, o′-dimethylene-(tris-p-cresyl)-bicyclophosphite (BCP, 1) has been investigated in solution by NMR, semi-empirical quantum mechanical, and molecular mechanics calculations. 1H and 31P NMR spectroscopic data show that when the BCP/Rh ratio exceeds 2, Rh hydride complexes of the composition RhH(BCP)3 and RhH(BCP)4 are formed. The source of the hydride ion is the ligand itself; most probably, H− originates from the bridging CH2 groups of BCP. The chemical shifts of these protons are sensitive to complexation due to the considerable electron density of HOMO and LUMO at one of the bridging CH2 moieties. Molecular mechanics simulations of the molecular structure of these complexes show that two cavities are formed in [Rh(BCP)3]+ by the aromatic rings of the ligands. These cavities may alternatively open and close, thus providing for a flexibly shielded catalytic site which explains the unusual catalytic behaviour of Rh complexes with BCP in hydrogenation and hydroformylation reactions.

The data of temperature-programmed desorption of ammonia from the surface of oxide systems and IR spectroscopy were used to demonstrate that the strength of the surface acid sites in titanium oxides prepared by the alkoxo method and modified by aluminum decreases with respect to that in nonmodified titanium oxide. Modification of titanium oxide with P3+ ions from ethriol phosphite almost completely suppresses the acid properties. Modified oxides are able to chemisorb water. XANES data suggest that modification of titanium oxide with phosphorus ions increases the electron density on the titanium atoms and, correspondingly, the basicity of the materials.

The redox properties of heterogenized RhI, RhII, and RhIII complexes with different, particularly organophosphorus, ligands were studied by cyclic voltammetry (CVA). The support is a carbon-paste electrode based on a fibrous-carbon material and activated carbon. The electrochemical reduction of RhIII produces Rh metal, which further catalyzes hydrogen evolution. After the reduction of water-soluble binuclear RhII complexes, the CVA curves exhibit peaks of electrocatalytic hydrogen evolution and irreversible RhI→RhII oxidation. The RhII complexes with organophosphorus ligands are characterized only by the peak of RhI→RhII oxidation. After reduction, the RhI complexes behave as a pseudo-reverse Rh0/RhI pair. The electron-donating properties of the ligand determine the reversibility of the system. The degree of structurization of the carbon matrix and the presence of phosphorus(v) atoms in it affect the electrochemical activity of the RhII and RhI complexes.

Hexaalkylphosphorous triamides form in good yields 6-dialkylamino-12H-dibenzo[d.g] [1,3,2]dioxaphosphocins 2a-i in the reaction with oligophenols 1a-i. Heating the stencal hindered compounds 2a-f up to 315°C leads to the corresponding bicyclic phosphites 3a-d while the non-hindered phosphocins 2g-i react in refluxing xylene to give phosphites 3e-g. The phosphocin 2i formed another phosphocin 2i* during heating to 90°C in THF by “wandering” of the phosphorus moiety. The bicyclic phosphites 3h and 3i were prepared starting from tetraphenol 1h and pentaphenol 1i by reaction with hexaethylphosphorous triamide in refluxing xylene. The diphosphorylated triphenol 4 and tetraphenol 5 are formed in the reaction of the corresponding phenols with 2 eq. of hexaalkylphosphorous triamide.

The formation of adducts in the system containing Rh2(OAC)4, cyclic amidophosphite [El2NPO(CH2)3O] and bicyclic phosphite [P(OCH2)3CEt] have been studied using low temperature 31P NMR. Varying the concentration of Rh2(OAc)4 made the signals due to a mono-adduct, a homoligated bis-adduct and a mixed bis-adduct observable in the 31P spectra. Iterational optimisation of the parameters of the spectra of symmetric bis-adducts showed a very strong correlation between the values of the coupling constants 1JRhRh and3JPP. The spectrum of the asymmetric adduct (amidophosphite-Rh-Rh-phosphite) yielded a well defined estimate of 3JPP. This value (793 Hz) is found to be between the values of the coupling constants for phosphite-phosphite and phosphite-phosphine interactions found by Boyar and Robinson. The integrals of the lines in the 31P spectra of the samples derived from different starting concentrations of Rh2(OAc)4 yielded values for the stability constants of the detected adducts. The mono-adduct of amidophosphite was found to be significantly more stable than that of phosphite.

A bicyclic phosphite, 4-ethyl-2,6,7-trioxa-1-phosphabicyclo [2.2.2]octane (1) was used for the complex formation with dirhodium(II) tetraacetate. Under the mole ratio P/Rh2 = 2, the reaction leads to an axial adduct (AcO)4Rh2L2. An excess of the phosphite (P/Rh2 = 20) causes the rupture of the metalmetal liaison, reduction of Rh(II) to Rh(I), and formation of a coordinatively unsaturated complex (RhL3)+ AcO−, which presents a new phenomenon. The complex was identified by low-temperature 31P NMR spectroscopy.

The reactivities of cyclophosphite precursors in alkoxo syntheses involving titanium(iv) tetra(n-butoxide) were studied by 31P NMR and IR spectroscopy. 2-Diethylamido-4-methyl-1,3,2-dioxaphosphinane and 4-ethyl-2,6,7-trioxaphosphabicyclo[2.2.2]octane in benzene are inert toward Ti(OBu)4. Gelation is accompanied by hydrolysis 2-diethylamido-4-methyl-1,3,2-dioxaphosphinane to give the corresponding hydrophosphoryl compound, while 4-ethyl-2,6,7-trioxaphosphabicyclo[2.2.2]octane remains intact during gelation.

The hydrolytic activity of ethriol phosphite and triphenyl phosphite in the p-xylene/water two-phase system was studied by the31P NMR method. It was shown that the rate of hydrolysis can be controlled by varying the pH of the aqueous phase. Hydrolysis of triphenyl phosphite is much slower than that of ethriol phosphite in the tested pH range. Coordination of ethriol phosphite with a rhodium carbonyl complex completely suppresses its hydrolysis.

A study has been made of the asymmetric hydrosilylation of acetophenone by diphenylsilane under the influence of rhodium complexes with chiral phosphites. The enantioselective nature of the reaction depends on the phosphite structure, the acetophenone/rhodium and ligana/rhodium ratios, and the temperature. The maximum optical yield (24%) is attainod on the complex [Rh(COD)Cl]2/(S, S)-2-ethoxy-4,5-dicarbisopropoxy-1,3-2-dioxophiospholane.

The influence of the nature of the organophosphorus ligand and the P/Rh molar ratio on the catalytic properties of rhodium carbonyl complexes in hydroformylation of 2-butenes was studied. The difference between phosphine and phosphite ligands during the formation of highly selective catalytic complexes was found. It was supposed that a decrease in the selectivity with respect to 2-methylbutanal is due to the isomerization of olefins under conditions of a decrease in the competitive capability of CO for coordination sites (the high P/Rh ratio, a decrease in the total pressure of the synthesis-gas).

The factor responsible for the deactivation of a carbonyl triphenylphosphite rhodium hydroformylation catalyst appears to be the formation of a chelate-structure complex with diphenylphosphite, which is the product of partial hydrolysis of the organophosphorus ligand. The deactivating effect of diphenylphosphite can be suppressed upon interaction of the H(O)P(OPh)2 and P(OPh)3-modified complex with 2-butenes under hydroformylation reaction conditions.

Complete transligation of (AcO)4Rh2 with 4-ethyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane was conducted in the solid phase on λ-Al2O3. The reduction of Rh11 to RhI on λ-Al2O3 at 130°C under the actionof the above-mentioned bicyclic phosphite is accompanied by the oxidation of the acetate anion to the acetoxyl radical. The oxidation products were detected by IR and ESR spectroscopy. 2,6-Di-tert-butyl-4-methylphenol was used as a “spin trap” to identify stable secondary radical cations.

It was demonstrated that the catalyst system based on acacRh(CO)2 and polyorgano-siloxanes exhibits high activity and stability in hydroformylation of 1-hexene. The effects of the nature of the oligomer, the ratio of oligomers, and the oligomer: rhodium ratio in the polymer on the synthesis and catalytic properties of the system were studied.

Wood residue crumbling with a rotary-pulse device is considered. Structural analysis of the resulting materials is carried out.

A topical trend in the industrial and ecological development of Russia is elaboration of the methods for integrated use of all components of natural raw materials, in particular, woodbased biomass. Note that the integrated processing of the woodbased bio� mass is possible only in close cooperation of various woodbased industries. These include production of traditional materials, energy sources, chemical prod� ucts, and biologically active compounds approaching the geochemically and energetically closed cycle tech� nology. Currently, all woodbased industries related to either mechanical or chemical processing of wood produce specific wastes although in different amounts. The difficulty of targeted standardized processing of these wastes is related to the necessity of strict indus� trial classification of the wastes and their averaging taking into account the physicochemical properties of the substances that form the material and parts of the trees. It is important that bulky wastes of woodbased biomass are formed upon extraction from wood of bio� logically active compounds such as terpenes, polypre� nols, and flavonoids, which are usually present in small amounts in the initial raw material (1). For example, the larch wood remainders after the removal of arabinogalactan and dihydroquercetin are large� scale wastes, their weight being about 85% of the wood weight (2, 3). A promising method for waste wood recycling is the production of plate materials without or with mini� mized use of synthetic binders. This trend is promising as regards the environmental safety of constructional materials. It was proposed to manufacture plate mate� rials from the compression molding material resulting from the extensive physicomechanical modification of wood by explosive autohydrolysis occurring at elevated

It was shown previously that the larch wood waste can be efficiently processed by passing as aqueous pulp through a disintegrator of cavitator type [1, 2]. By this procedure the wood waste is transformed into a new polymer material called “Cavitated wood.” Besides the cavitated wood, therewith are formed lowmolecular substances: the dihydroquercetin flavonoid, terpenes, terpenoids, etc. [2]. Apparently, the essence of the phenomenon lies in the reorganization of the polymer structure of the original wood raw material, by moving some of its –Ar–C–C–C–X nano-sized blocks. Let us call this lignin nano-isomerization.

s The hydroformylation of olefins in presence catalytic systems on a basis RhCl3*3H2O and a copolymer of styrene with 4-N-pyrrolidinopyridine units in a main chain and acacRh(CO)2 and polymeric organosiloxanes was investigated. These catalytic systems have high stability and activity. The hydroformylation of isobutylene in the presence of such systems proceeds with high speed in conditions, when traditional homogeneous catalysts unactivity. It was showed by ESCA, that complexing of rhodium with pyrrolidinopyridine units of copolymer occurs on atom of nitrogen of pyridine ring. The influence of composition and structure of polymeric supports on creation of active centers of catalysts and their catalytic properties was investigated. The influence of solvents on catalytic properties of polymeric catalysts was studied.

Ligand L I was obtained by the reaction of the diisopropyl ester of (+)-tartaric acid with P(NMe2)2OEt in i:i mole ratio at 120~ Ligand L 2 was obtained by the reaction of the (-)-menthol with di(o,o-di-tert-butyl-p-methyl)phenyl chlorophosphite in absolute benzene at 0~ Both these compounds were characterized by IH, 13C, and 31p NMR and IR spectroscopy and physicochemical indices. Catalysts were obtained in situ from [Rh(COD)CI]z and [RH(CO)2CI]z with L I and L 2. The experiments were carried out in a reactor maintained at constant temperature in an argon atmosphere. The experiment indicated by an asterisk was carried out in CCI 4. The other reactions were carried out without solvent. As shown previously, the reaction temperature and acetophenone:rhodium (AP/Rh) and ligand:rhodium (L*/Rh) ratios affect the enantioselectivity of the catalyst [2]. The results are given in Fig. I. l-Phenylethanol was obtained when the reaction was carried out with the rhodium complexes with L I in optical yield up to 23%. This is the first example of the successful use of phosphite complexes in asymmetric hydrosilylation.

The paper is concerned with rhodium(1) complexes of the type acacRh(CO)L, Rh(CO)ClL2, [Rh(CO)LCl]2, [acacRh(CO)[2L and [Rh(CO)LCl]n, where L: P are monodentate, P,N- and P,P-bidentate ligands including 1,3,2-diheterophospholane and phosphorinane cycles In our studies two synthetic approaches were used, viz. the interaction of tricoordinated phosphorus derivatives with the starting rhodium substrate proceeding via the associative mechanism and the reaction of pentacoordinated phosphorus derivatives (hydrospirophosphoranes) 31P, 1H, 13C NMR, IR spectroscopy as well as X-ray and chemical studies of rhodium-coordinated 1,3,2-diheterophos-phacyclanes were carried out. The properties of these organophosphorus ligands were shown to depend on the nature and configurational rigidity of the substituents X, Y, Z at the phosphorus atom. This is illustrated by the dependence of 1J(Rh, P) and ν (CO) on the size of the phosphorus ring and the position of the heteroatoms (O, N) in the ligand molecule.

Glycoamidophosphites in the pentose series have been synthesized based on 2,3-O-isopropylidene-β-methyl-D-ribofuranoside, 1,2-O-isopropylidene-α-D-xylofuranose, xylitane and 3,5-O-isopropylidenexylitane. Some of these compounds are used as ligands for the synthesis of the palladium complexes. Consideration is given to the behavior of these complexes as catalysts in the asymmetric hydrogenation of itaconic acid.

Neutral mono- and di-nuclear carbonyl 2-amino-1,3,2-dioxaphosphorinane rhodium complexes of types RhCl(CO)L2 and [RhCl(CO)L]2 have been synthetized. The complexing process in the [RhCl(CO)2]2-phosphcrinane system has been investigated at different molar ratios of reagents by means of 31P NMR spectroscopy. The dinuclear phosphorinane complexes, in contrast to mononuclear ones, exhibit activity in the catalytic hydrogenation of olefins.

1. A phosphine-palladium complex catalyst has been proposed for carbonylation of piperidine to N-for-mylpiperidine in the absence of solvent. The catalyst has high stability. 2. A mechanism for activation of the CO molecule has been proposed, which involves formation of a radical anion in the coordination sphere of the complex and its subsequent reaction with piperidine to form N-for-mylpiperidine.