Multifunctional nano particulate systems based on hydroxyapatite as systems for local delivery of vitamin D3

Multifunctional drug delivery system based on hydroxyapatite may be a research challenge in the treatment and reconstruction of bone tissue. Vitamin D3 has a positive effect on osteogenesis as it increases osteoblast differentiation and mineralization of bone tissue. The purpose of the study presented in this paper has been to examine the possibility of the synthesis of a new multifunctional nanoparticulate system for local delivery of vitamin D3 suitable for applications in bone engineering. The synthesis, characterization and application of three nano particle systems was shown: hydroxyapatite, hydroxyapatite/vitamin D3 and hydroxyapatite/PLGA/vitamin D3. The obtained vitamin D3-loaded nanoparticles based on hydroxyapatite. Characterization was performed with wide-angle X-ray structural analysis (XRD), infrared spectroscopy (FT-IR), field-emission scanning electron microscopy (FESEM), zeta potential (ZP) and particle sized distribution (PSD) methods. Basic in vitro studies were performed implantation of materials in rats. XRD and FT-IR analyses confirmed that the vitamin D3 is loaded hydroxyapatite and PLGA. Different values of zeta potential may refer to different phenomenological processes during in vivo studies

Effects of solvent and structure on the reactivity of 2-substituted nicotinic acids with diazodiphenylmethane in aprotic solvents

The rate constants for the reactions of diazodiphenylmethane (DDM) with 2-substituted nicotinic acids in nine aprotic solvents at 30°C were determined. The obtained second order rate constants in aprotic solvents, were correlated using the Kamlet-Taft solvatochromic equation in the complete form: log k = log k0 + s

Synthesis, characterization and antioxidative activity of 1,3-dihydro-3-[4-substituted-(phenylmethyl)imino]-2H-indole-2-ones

Izvršena je sinteza četiri 1,3-dihidro-3-[4-supstituisanih-(fenilmetil)imino]-2H-indol-2-ona i to: 1,3-dihidro-3-[(fenilmetil)imino]-2H-indol-2-ona, 1,3-dihidro-3-[4-brom-(fenilmetil)imino]-2H-indol-2-ona, 1,3-dihidro-3-[4-hidroksi-(fenilmetil) imino]-2H-indol-2-ona, 1,3-dihidro-3-[4-metoksi-(fenilmetil)imino]-2H-indol-2-ona, kao i jedinjenja slične strukture, 1,3-dihidro-3-[(2-feniletil)imino]-2H-indol-2-ona. Urađena je karakterizacija sintetisanih jedinjenja primenom FTIR spektroskopije, određivanjem temperature topljenja i elementalnom analizom, nakon čega je izvršeno ispitivanje antioksidativne aktivnosti svih pet jedinjenja. Antioksidativna aktivnost je određena primenom DPPH (1,1-difenil-2-pikril-hidrazil radikal) metode, u cilju određivanja najefikasinijeg jedinjenja od značaja za dalje istraživanje.The synthesis of 1,3-dihydro-3-[4-substituted-(phenylmethyl)imino]-2H-indole-2-ones: 1,3-dihydro-3-[(phenylmethyl)imino]-2H-indol-2-one, 1,3-dihydro-3-[4-bromo-(phenylmethyl)imino]-2H-indol-2-one, 1,3-dihydro-3-[4-hydroxy-phenyl-methyl)imino]-2H-indol-2-one, 1,3-dihydro-3-[4-methoxy-(phenylmethyl)imino]-2H-indol-2-one, as well as of the compound of similar structure, 1,3-dihydro-3-[(2-phenylethyl)imino]-2H-indol-2-one, was performed. The characterization of the obtained five compounds was carried out using FTIR, melting points and elemental analysis. Their antioxydative activity was then tested by DPPH (2,2-diphenyl-1-picrylhydrazyl radical) method and the results were compared in order to determine the most efficient compound, significant for further research

Synthesis, characterization and antioxidative activity of aminolysis products of Hantzsch dihydropyridines

Supstituisani estri 1,4-dihidropiridina (1,4-DHP) nastaju u reakciji etil-acetoacetata i odgovarajućih supstituisanih aldehida u prisustvu amonijaka. Nastali estri sa primarnim aminima formiraju amide. Serija amida nastalih od navednih jedinjenja je sintetisana sa namerom da se ispitaju njihove karakteristike i antioksidativna aktivnost. U ovde prikazanom istraživanju za aminolizu upotrebljen je 2-aminotiazol. Antioksidativna aktivnost je ispitivana DPPH (2,2-difenil-1-pikrilhidrazil-radikal) i ABTS (2,2'-azino-bis(3-etilbenzotiazolin-6-sulfonska kiselina)) metodama, a pored toga određene su tačke topljenje, snimljeni IR spektri i izvršena je elementalna analiza.The substituted esters of 1,4-dihydropyirdines (1,4-DHP) are formed in the reaction of ethyl acetoacetate and corresponding substituted aldehydes in the presence of ammonia. Amides form from esters of substituted 1,4-DHP by aminolysis employing primary amines. A series of amides of the mentioned compounds was synthesized with the aim to analyze their chemical properties and antioxidative activity. The amine used in the present research was 2-aminothiazole. The antioxidative activity was determined by DPPH (2,2-diphenyl-1-picrylhydrazyl radical) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) methods; melting points and IR were measured and elemental analysis was performed

The effects of solvents and structure on the electronic absorption spectra of the isomeric pyridine carboxylic acid N-oxides

The ultraviolet absorption spectra of the carboxyl group of three isomeric pyridine carboxylic acids N-oxides (picolinic acid N-oxide, nicotinic acid N-oxide and isonicotinic acid N-oxide) were determined in fourteen solvents in the wavelength range from 200 to 400 nm. The position of the absorption maxima (λmax) of the examined acids showed that the ultraviolet absorption maximum wavelengths of picolinic acid N-oxide are the shortest, and those of isonicotinic acid N-oxide acid are the longest. In order to analyze the solvent effect on the obtained absorption spectra, the ultraviolet absorption frequencies of the electronic transitions in the carboxylic group of the examined acids were correlated using a total solvatochromic equation of the form max = v0 + sπ + aα+ bβ, where υmax is the absorption frequency (1/λmax), p is a measure of the solvent polarity, β represents the scale of solvent hydrogen bond acceptor basicities and α represent the scale of solvent hydrogen bond donor acidities. The correlation of the spectroscopic data was carried out by means of multiple linear regression analysis. The solvent effects on the ultraviolet absorption maximums of the examined acids were discussed

Application of polymer materials for production of evaporative pattern and development of new casting process

In this paper, results of the investigation of the polymer materials for evaporate patterns and their application in the new casting method (EPC process) are presented. The basic characteristic of EPC process is that patterns and gating of moulds, made of polymers, stay in the cast till the liquid metal inflow. In contact with liquid metal, intensely, in relatively short time, polymer pattern is been decomposing and evaporating , accompanied by castings crystallization. In order to achieve qualitative and profitable castings production by the EPC process it is necessary to reach the balance in the system: evaporable polymer pattern-liquid metal-refractory coat-sandy cast in the phase of metal inflow, decomposition and evaporation of polymer pattern, formation and soldification of castings. Results of this investigation of this process relate on application of puffed polystyrene of various densities (kg/m3): 18, 20, 25. Application of lower density polymer (20 kg/m3) gave positive results on structure and properties of silumina castings obtained using this casting method

Određivanje klopidogrela voltametrijom sa pravouglim impulsima na elektrodi od zlata

The determination of clopidogrel, an antiplatelet agent, was performed at a gold electrode in pH 3.7 acetate buffer using cyclic voltammetry (CV) and square wave voltammetry (SWV). Each voltammogram was characterized by the well defined peak at approximately 1.0 V. The current of anodic stripping peak exhibited a linear dependence on the clopidogrel concentration in the range from 317.89 to 935.16 μg cm-3. The obtained linearity was applied to determine clopidogrel in the tablet form of the pharmaceutical preparation (Plavix®). The results were compared to the UV spectrophotometric and HPLC methods. .Klopidogrel je antitrombotski agens iz tijenopiridinske klase, koji se koristi za inhibiranje formiranja krvnih ugrušaka pri lečenju koronarne arterijske bolesti, periferne vaskularne bolesti, i cerebrovaskularne bolesti. Elektrohemijsko ponašanje klopidogrel standarda i kao sastojka tablete Plavix® je definisano cikličnom voltametrijom. Njihovo kvantitativno određivanje na elektrodi od zlata u acetatnom puferu, pH 3,7, urađeno je voltametrijom sa pravougaonim impulsima (SWV). Pokazano je obema tehnikama da je svaki voltamogram okarakterisan dobro definisanim strujnim vrhom na 1,0 V. Na osnovu linearne zavisnosti anodnih struja od koncentracije klopidogrel standarda određena je masa klopidogrela u Plavix® tableti. Dobijeni rezultati pokazuju da SWV tehnika može biti korišćena direktno, brzo i jednostavno za određivanje klopidogrela u tabletama. Rezultati dobijeni SWV voltametrijskom tehnikom su poređeni sa rezultatima analize klopidogrela UV spektrofotometrijom i tečnom hromatografijom sa visokim performansama. Analitički rezultati pokazuju da je masa aktivne supstance u tabletama Plavix® u okviru limita specifikovanog farmakopejom. To ukazuje da voltametrija sa pravougaonim impulsima može biti uspešna alternativa hromatografskim i spektrofotometrijskim metodama.

Uticaj rastvarača i strukture na reaktivnost 6-supstituisanih nikotinskih kiselina sa diazodifenilmetanom u aprotičnim rastvaračima

The rate constants for the reactions of diazodiphenylmethane (DDM) with 6-substituted nicotinic acids in aprotic solvents at 30°C were determined. The obtained second order rate constants in aprotic solvents, together with literature data for benzoic and nicotinic acids in protic solvents, were used for the calculation of solvent effects, employing the Kamlet-Taft solvatochromic equation (linear solvation energy relationship - LSER) in the form: log k = log k0 + + sΠ*+ aα + bβ. The correlations of the kinetic data were performed by means of multiple linear regression analysis taking appropriate solvent parameters. The sign of the equation coefficients (s, a and b) were in agreement with the postulated reaction mechanism, and the mode of the solvent influences on the reaction rate is discussed based on the correlation results. A similar contribution of the non-specific solvent effect and electrophilic solvation was observed for all acids, while the highest contribution of nucleophilic solvation was influenced by their high acidity. Correlation analysis of the rate data with substituent óp parameters in an appropriate solvent using the Hammett equation was also performed. The substituent effect on the acid reactivity was higher in aprotic solvents of higher dipolarity/polarizability. The mode of the transmission of the substituent effect is discussed in light of the contribution of solute-solvent interaction on the acid reactivity.Konstante brzina 6-supstituisanih nikotinskih kiselina sa diazodifenilmetanom (DDM) su određene u različitim protičnim i aprotičnim rastvaračima na 30°C. Izračunate konstante brzina, kao i literaturni podaci, korišćeni su za izračunavanje efekata rastvarača korišćenjem Kamlet-Taft-ove solvatohromne jednačine. Konstante brzina su korelisane sa parametrima rastvarača korišćenjem Kamlet-Taft-ove jednačine oblika: log k = log k0 + + sΠ*+ aα + bβ. Korelacije dobijenih kinetičkih rezultata sa odgovarajućim parametrima rastvarača su izvedene primenom metode višestruke linearne regresione analize. Znak koeficijenata (s, a i b) u dobijenim korelacijama je u saglasnosti sa reakcionim mehanizmom. Sličan doprinos nespecifičnih efekata i elektrofilne solvatacije rastvarača je uočen za sve ispitivane kiseline, a najveći doprinos nukleofilne solvatacije polaznog stanja je posledica visoke kiselosti ispitivanih kiselina. Uticaj rastvarača na vrednosti reakcionih konstanti je diskutovan na osnovu dobijenih korelacionih rezultata. Korelaciona analiza konstanti brzina sa óp konstantama supstituenata, u ispitivanom rastvaraču, izvršena je primenom Hammett-ove jednačine. Efekti supstituenata na reaktivnost ispitivanih kiselina su značajniji u aprotičnim rastvaračima visoke dipolarnosti/polarizabilnosti. Način prenosa efekata supstituenata je diskutovan u svetlu doprinosa interakcija rastvorak-rastvarač na reaktivnost ispitivanih kiselina

Efekti strukture i rastvarača na reaktivnost 2-supstituisanih nikotinskih kiselina sa diazodifenilmetanom u aprotičnim rastvaračima

The rate constants for the reactions of diazodiphenylmethane (DDM) with 2-substituted nicotinic acids in nine aprotic solvents at 30°C were determined. The obtained second order rate constants in aprotic solvents were correlated using the Kamlet-Taft solvatochromic equation in the complete form: log k = log k0 + sπ*+ a( + bβ. The correlations of the kinetic data were realized by means of multiple linear regression analysis. The obtained results were analyzed in terms of the initial and the transition state of the reaction and compared with previously determined kinetic data for nicotinic acid. The signs of the equation coefficients (s, a and b) are in agreement with the reaction mechanism and the influence of the solvent on the reaction rate is discussed based on the correlation results. The mode of the transmission of the substituent effect is discussed in light of the contribution of solute-solvent interaction to the reactivity of the acid. The substituent effect was additionally analyzed by the Hammett equation, log k = pσ + log k0.Konstante brzine za reakciju diazodifenilmetana (DDM) sa 2-susptituisanim nikotinskim kiselinama u devet aprotičnih rastvarača su određene na 30 °S. Dobijene konstante brzine za reakciju drugog reda su korelisane Kamlet-Taftovom totalnom solvatohromnom jednačinom u obliku: log k = log k0 + sπ*+ a( + bβ. Korelacija kinetičkih podataka izvršena je višestrukom linearnom regresionom analizom. Dobijeni rezultati su analizirani u odnosu na osnovno i prelazno stanje i upoređeni sa ranije određenim vrednostima za nesupstituisanu kiselinu. Znaci ispred koeficijenata u jednačini su u skladu sa pretpostavljenim mehanizmom reakcije. Diskutovan je prenos efekata supstituenata na reakcioni centar uzimajući u obzir doprinos efekata rastvarača na reaktivnost ispitivanih jedinjenja. Efekat supstituenata je dodatno analiziran Hametovom jednačinom: log k = pσ + log k0

Reversed substituent effect on C=O stretching vibrations in hydantoin derivatives

The infrared spectra have been recorded for thirteen 3-substituted-5,5-dimethylhydantoins in the region of fundamental C=O stretching vibrations in dichloromethane. The frequencies of symmetric and asymmetric C=O stretching vibrations are correlated with Taft's sigma* substituent constants. When the electron-releasing substituents are in position-3 in the hydantoin ring the stretching frequency increases with the increase in the electronegativity. However, the effect of electron-withdrawing substituents appears to be quite opposite, i.e. the carbonyl stretching vibrations are decreased. The correlations with extended Hammett equation Q(x) = alpha sigma(1) + beta sigma(R) + h and with Swain-Lupton equation p(ij) = fF + rR + h give the results which according to Jaffe can be considered as poor. The correlation obtained from Hammett sigma(p) constants furnish satisfacory results except the substituents with a wide range of polarity. The mechanism of the transmission of substituent effects in hydantoin systems is discussed considering the results of above mentioned observations