Kinetics, Equilibrium, and Thermodynamics for Conjugation of Chitosan with Insulin-Mimetic [meso-Tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadate(IV)(4-) in an Aqueous Solution.

This study investigated the conjugation of chitosan with the insulin-mimetic [meso-tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadate(IV)(4-), VO(tpps), in an aqueous medium as a function of conjugation time, VO(tpps) concentrations, and temperatures. To validate the synthesis of chitosan-VO(tpps) conjugate, UV-visible and Fourier transform infrared spectrophotometric techniques were utilized. Conjugate formation is ascribed to the electrostatic interaction between the NH3+ units of chitosan and the SO3- units of VO(tpps). Chitosan enhances the stability of VO(tpps) in an aqueous medium (pH 2.5). VO(tpps) conjugation with chitosan was best explained by pseudo-second-order kinetic and Langmuir isotherm models based on kinetic and isotherm studies. The Langmuir equation determined that the maximal ability of VO(tpps) conjugated with each gram of chitosan was 39.22 µmol at a solution temperature of 45 °C. Activation energy and thermodynamic studies (Ea: 8.78 kJ/mol, ΔG: -24.52 to -27.55 kJ/mol, ΔS: 204.22 J/(mol K), and ΔH: 37.30 kJ/mol) reveal that conjugation is endothermic and physical in nature. The discharge of VO(tpps) from conjugate was analyzed in freshly prepared 0.1 mol/L phosphate buffer (pH 7.4) at 37 °C. The release of VO(tpps) from the conjugate is a two-phase process best explained by the Higuchi model, according to a kinetic analysis of the release data. Taking into consideration all experimental findings, it is proposed that chitosan can be used to formulate both solid and liquid insulin-mimetic chitosan-VO(tpps) conjugates.

Therapeutic role of hesperidin in collagen-induced rheumatoid arthritis through antiglycation and antioxidant activities.

Rheumatoid arthritis (RA), a chronic inflammatory disease, and its exact aetiology is not defined clearly. The free radicals produced in large amount in RA are associated with alteration in molecular structure resulting in glycation of proteins. As a result of glycation, advanced glycation end products (AGEs) produced. In this study, collagen type II suspension was injected into Wistar rats to make RA model of rats. Simultaneously, hesperidin 50 mg kg-1 body weight was orally administrated to the rats for 21 days. X-rays of the rat hind paws were analyzed and found to be significantly effective against bone loss after treatment with hesperindin. Nε -(carboxymethyl)lysine (CML) and pentosidine (PTD) concentrations in collagen-induced RA plasma were determined as 565.29 ± 30.15 and 37.23 ± 1.02 ng ml-1 , respectively, while CML and PTD in IgG were 6.63 ± 0.44 ng mg-1 IgG and 425.33 ± 37.26 ng g-1 IgG, respectively. After treatment with hesperidin, the elevated levels of CML in plasma and in IgG were significantly (p < 0.001) lowered to 450.95 ± 15.05 mg ml-1 and 5.23 ± 0.27 ng mg-1 IgG, respectively. Similarly, concentrations of PTD in plasma and IgG of rats treated with hesperidin were 28.46 ± 1.20 ng ml-1 and 359.35 ± 31.11 ng g-1 IgG, respectively. Thus, after treatment with drug, plasma CML and IgG PTD levels were restored as 93% and 16%, respectively, through free radical scavenging activity of hesperidin resulting in alleviation of RA disease by decreasing the AGEs concentrations. Therefore, use of hesperidin may be useful to alleviate severity of RA disease.

Adsorption Characteristics of Allura Red AC onto Sawdust and Hexadecylpyridinium Bromide-Treated Sawdust in Aqueous Solution.

The Allura red AC (ARAC) dye adsorption onto natural sawdust (NSD) and hexadecylpyridinium bromide-treated sawdust (MSD) was investigated in aqueous solution as a function of contact time, solution pH, particle size, adsorbent dosage, dye concentration, temperature, and ionic strength. The adsorbents were characterized by Fourier transform infrared spectroscopy and X-ray diffraction crystallography. The dye adsorption onto both adsorbents was confirmed by field emission scanning electron microscopy and energy-dispersive X-ray spectroscopy. The maximum dye adsorption was found within 120 min at pH 2.0 for NSD and pH 3.0 for MSD, respectively, with a particle size of 0-75 µm and an adsorbent dosage of 0.07 g/50 mL ARAC dye solution (50 µmol/L). The batch adsorption kinetic data were followed by the pseudo-second-order kinetic model rather than the pseudo-first-order and Elovich kinetic models. Equilibrium adsorption isotherms were explained by the Langmuir isotherm model, and the maximum extent of adsorption was found to be 52.14 µmol/g for NSD and 151.88 µmol/g for MSD at 55 °C. The values of activation energy (E a) and thermodynamic parameters (ΔG ⧧, ΔH ⧧, ΔS ⧧, ΔG°, ΔH° and ΔS°) proved that the ARAC dye adsorption onto both adsorbents NSD and MSD is a spontaneous-endothermic physisorption process. ARAC (98-99%) was released from dye-loaded adsorbents in aqueous solution (pH ≥ 12) within 120 min. The adsorbents NSD and MSD were reused for a second time without significant loss of their adsorption efficiency.

Antidiabetic activity of the orally effective vanadyl-poly (gamma-glutamic acid) complex in streptozotocin(STZ)-induced type 1 diabetic mice.

Newly synthesized vanadyl-poly(gamma-glutamic acid) complex (VO-gamma-PGA) with a VO(O4) coordination mode was found to have potent antidiabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice (STZ-mice), compared with that of a solution containing only vanadyl sulfate, VOSO4. This was the first example of orally active vanadyl complex of gamma-PGA for treating STZ-mice. To better define its efficacy, we examined here the effects of VO-gamma-PGA treatment in STZ-mice by oral administration at the dose of 10 mg V/kg body mass for a longer period time than our previous study. The improvement in diabetic states in STZ-mice compared with saline-treated nondiabetic normal Std ddY mice. It was found that the elevated blood glucose levels in STZ-mice significantly decreased after 3 days and sustained the normalized blood glucose level around 180-200 mg/dL (10-11.1 mM) for the last 14 days, which is close to the blood glucose levels 100-200 mg/dL (5.6-11.1 mM) in nondiabetic normal Std ddY mice. The improvement in diabetes was strongly corelated by the improvement in oral glucose tolerance ability, glycosylated hemoglobin (HbA1c) levels and blood pressure, and serum parameters. The present results confirmed that VO-gamma-PGA complex is a promising, orally active insulin-mimetic agent to treat type 1 diabetic mice.

Chelation of vanadium(V) by difluoromethylene bisphosphonate, a structural analogue of pyrophosphate.

The structural and functional analogy between difluoromethylene bisphosphonate (CF2PP) and pyrophosphate (PPi) is investigated in a reaction with V(V) in the form of vanadate. The reaction of CF2PP with vanadate was investigated using 1.00 M KCl as supporting electrolyte over the ranges 3 < or = [CF2PP] < or = 60 mM and 2.06 < or = pH < or = 11.80. 51V, 19F, and 31P NMR spectroscopic studies showed that a 1:1 species was formed with an H+-dependent formation constant of 110 M-1 at pH 7.22. Results of solution experiments and ab initio calculations are consistent with CF2PP coordinating V(V) in a bidentate manner, as previously reported for PPi. Below pH 4, a minor complex forms, which is consistent with a 1:2 stoichiometry. This complex was also observed with pyrophosphate. The X-ray crystal structure of the monoprotonated difluoromethylene bisphosphonate anion (H[CF2PP]3-)-toludine complex is presented. The H[CF2PP]3- anion crystallized in the triclinic space group P with a = 12.7629(7) A, b = 13.3992(7) A, c = 17.1002(9) A, and V = 2584.4(2) A3, and Z = 2. Sheets of the layers of anions are connected through a network of H-bonds and separated by a layer of toludine cations. The structural features are investigated, and the CF2PP anion was found to be longer and wider than the corresponding PPi. Given the larger size of this anion compared to PPi, the chelation affinity upon CF2 substitution was found to be 4-5-fold reduced at neutral pH.

Improvement of hyperglycaemia and metabolic syndromes in type 2 diabetic KKAy mice by oral treatment with [meso-tetrakis(4-sulfonatophenyl) porphyrinato]oxovanadium(IV)(4-) complex.

Recently, we reported that [meso-tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadium(IV)(4-), VO(tpps), shows in-vitro insulin-mimetic and in-vivo anti-diabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice. This result prompted us to examine its ability in type 2 diabetic model KKA(y) mice with insulin resistance. We studied the in-vivo anti-diabetic activity of VO(tpps), compared with that of vanadium(IV) oxide sulfate, VS, as control. Both compounds were orally administered at doses of 5-10 mg (0.1-0.2 mmol) V/kg body weight to the KKA(y) mice for 28 days. VO(tpps) normalized the hyperglycaemia within 15 days, while VS lowered the blood glucose concentration only by a small degree. In addition, metabolic syndromes characterized by insulin and leptin resistance were significantly improved in VO(tpps)-treated KKA(y) mice compared with those treated with VS. The improvement in diabetes was validated by oral glucose tolerance test and decrease in HbA(1c) concentration. Based on these observations, VO(tpps) is proposed to be an orally active oxovanadium(IV)-porphyrin complex for treating not only type 2 diabetes but also metabolic syndromes in animals.

Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection.

Mechanisms and kinetics of trisodium 2-hydroxy-1,1'-azonaphthalene-3,4',6-trisulfonate adsorption onto chitosan.

Chitosan, a naturally abundant biopolymer, has widely been studied for metal adsorption from various solutions, but the extension of chitosan as an adsorbent to remove organic substances from water and wastewater has seldom been explored. In this study, the adsorption of an azo dye, trisodium 2-hydroxy-1,1'-azonaphthalene-3,4',6-trisulfonate (1), from aqueous solution onto the various degrees of deacetylated chitosan has been investigated. Equilibrium studies have been carried out to determine the capacity of chitosan for dye. The experimental data were analyzed using two isotherm correlations, namely, Langmuir and Freundlich equations. The linear correlation coefficients were determined for each isotherm and the Langmuir provided the best fit. The experimental adsorption isotherms were perfectly reproduced in the simulated data obtained from numerical analysis on the basis of the Langmuir model and the isotherm constants. Adsorption of (1) onto the chitosan flakes was found to be strongly depending on degrees of deacetylation in chitosan and temperatures. Significant amounts of (1) were adsorbed by chitosan 8B (higher degree of deacetylated chitosan), but the adsorption capacity was reduced remarkably with increasing solution temperatures. Thermodynamic parameters such as change in free energy (DeltaG), enthalpy (DeltaH), and entropy (DeltaS) were also determined. In addition, kinetic study indicated that the adsorption process mechanisms were both transport- and attachment-limited.

Kinetic simulation studies on the transient formation of the oxo-iron(IV) porphyrin radical cation during the reaction of iron(III) tetrakis-5,10,15,20-(N-methyl-4-pyridyl)-porphyrin with hydrogen peroxide in aqueous solution.

High-valent oxo-iron(IV) species are commonly proposed as the key intermediates in the catalytic mechanisms of iron enzymes. Water-soluble iron(III) tetrakis-5,10,15,20-(N-methyl-4-pyridyl)porphyrin (Fe(III)TMPyP) has been used as a model of heme-enzyme to catalyse the hydrogen peroxide (H(2)O(2)) oxidation of various organic compounds. However, the mechanism of the reaction of Fe(III)TMPyP with H(2)O(2) has not been fully established. In this study, we have explored the kinetic simulation of the reaction of Fe(III)TMPyP with H(2)O(2) and of the catalytic reactivity of FeTMPyP in the luminescent peroxidation of luminol. According to the mechanism that has been established in this work, Fe(III)TMPyP is oxidized by H(2)O(2) to produce (TMPyP)(*+)Fe(IV)[double bond]O (k1 = 4.5 x 10(4)/mol/L/s) as a precursor of TMPyPFe(IV)[double bond]O. The intermediate, (TMPyP)(*+)Fe(IV)[double bond]O, represented nearly 2% of Fe(III)TMPyP but it does not accumulate in sufficient concentration to be detected because its decay rate is too fast. Kinetic simulations showed that the proposed scheme is capable of reproducing the observed time courses of FeTMPyP in various oxidation states and the decay profiles of the luminol chemiluminescence. It also shows that (TMPyP)(*+)Fe(IV)[double bond]O is 100 times more reactive than TMPyPFe(IV)[double bond]O in most of the reactions. These two species are responsible for the initial sharp and the sustained luminol emissions, respectively.

Transient formation of the oxo-iron(IV) porphyrin radical cation during the reaction of iron(III) tetrakis-5,10,15,20-(N-methyl-4-pyridyl)porphyrin with hydrogen peroxide in aqueous solution.

The reaction of iron(III) tetrakis-5,10,15,20-(N-methyl-4-pyridyl)porphyrin (Fe(III)TMPyP) with hydrogen peroxide (H(2)O(2)) and the catalytic activity of the reaction intermediates on the luminescent peroxidation of luminol in aqueous solution were studied by using a double-mixing stopped-flow system. The observed luminescence intensities showed biphasic decay depending on the conditions. The initial flashlight decayed within <1 s followed by a sustained emission for more than 30 s. Computer deconvolution of the time-resolved absorption spectra under the same conditions revealed that the initial flashlight appeared during the formation of the oxo-iron(IV) porphyrin, TMPyPFe(IV) = O, which is responsible for the sustained emission. The absorption spectra 0.0-0.5 s did not reproduce well by a simple combination of the two spectra of Fe(III)TMPyP and TMPyPFe(IV) = O, indicating that transient species was formed at the initial stage. Addition of uric acid (UA) caused a significant delay in the initiation of the luminol emission as well as in the formation of the TMPyPFe(IV) = O. Both of them were completely diminished in the presence of UA equimolar with H(2)O(2), while mannitol had no effect at all. The delay of the light emission as well as the appearance of TMPyPFe(IV) = O was directly proportional to the [UA](0) but other kinetic profiles were not changed significantly. Based on these observations and the kinetic analysis, we confirmed the involvement of the oxo-iron(IV) porphyrin radical cation, (TMPyP)(.+)Fe(IV) = O, as an obligatory intermediate in the rate-determining step of the overall reaction, Fe(III)TMPyP + H(2)O(2) --> TMPyPFe(IV) = O, with a rate constant of k = 4.3 x 10(4)/mol/L/s. The rate constants for the reaction between the (TMPyP)(.+)Fe(IV) = O and luminol, and between the TMPyPFe(IV) = O and luminol were estimated to be 3.6 x 10(6)/mol/L/s and 1.31 x 10(4)/mol/L/s, respectively.