Tapan Kumar Saha

A Zinc(II)/Poly(γ-glutamic acid) Complex as an Oral Therapeutic for the Treatment of Type-2 Diabetic KKAy Mice

In developing new insulin-mimetic zinc(II) complexes with various ligands including a biodegradable polymer, we prepared and characterized a Zn(gamma-pga) complex in solution as well as in solid, and investigated its in vitro insulin-mimetic activity and in vivo antidiabetic effect in type-2 diabetic KKA(y) mice. The in vitro insulin-mimetic activity of the Zn(gamma-pga) complex was considerable better than that of ZnSO(4). The Zn(gamma-pga) complex normalized the hyperglycemia in KKA(y) mice within 21 d when administrated orally at doses of 10-20 mg (0.15-0.31 mmol) Zn per kg body mass for 30 d. In addition, the impaired glucose tolerance, elevated HbA(1c) levels and metabolic syndromes were significantly improved in Zn(gamma-pga)-treated KKA(y) mice relative to those administrated with saline and ZnSO(4).

In vitro insulin-mimetic activity and in vivo metallokinetic feature of oxovanadium(IV)porphyrin complexes in healthy rats

We prepared [meso-tetrakis(4-carboxylatophenyl)porphyrinato]oxovanadium(IV) tetrasodium, ([VO(tcpp)]Na4), and investigated its in vitro insulin-mimetic activity and in vivo metallokinetic feature in healthy rats. The results were compared with those of previously proposed insulin-mimetic oxovanadium(IV)porphyrin complexes and oxovanadium(IV) sulphate. The in vitro insulin-mimetic activity and bioavailability of [VO(tcpp)]Na4 were considerably better than those of [meso-tetrakis (1-methylpyridinium-4-yl)porphyrinato]oxovanadium(IV)(4+) tetraperchlorate ([VO(tmpyp)](ClO4)4) and oxovanadium(IV) sulphate. On the other hand, [VO(tcpp)]Na4 and [meso-tetrakis(4-sulfonatophenyl) porphyrinato]oxidovanadate(IV)(4-)([VO(tpps)]) showed very similar in vitro insulin-mimetic activity and in vivo metallokinetic feature in healthy rats. In particular, the order of in vitro insulin-mimetic activity of the complexes was determined to be: [VO(tcpp)]Na4 ≈ [VO(tpps)] > ([VO(tmpyp)](ClO4)4 > oxovanadium(IV) sulphate.

Studies on the mechanism of the reaction of tetrakis({1-me-thylpyridinium-4-yl}porphyrinato)iron(III) pentaperchlorate with hydrogen peroxide

The reaction of the 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrinatoiron(III) cation, [FeIII(TMPyP)]5+ (1; prepared as the pentaperchlorate), with hydrogen peroxide (H2O2) in aqueous solution was studied by spectrophotometric methods. The porphyrin 1 was rapidly oxidized with an excess of H2O2 under aerobic conditions to the oxo-iron(IV) porphyrin, [FeIVO(TMPyP)]4+ (2), having UV-visible absorption maxima at 436 and 450 nm. Computer deconvolution of the time-resolved absorption spectra revealed that the absorption spectra < 0.5 s were not reproduced well by a simple combination of the two spectra of 1 and 2, indicating that transient species were formed at the initial stage. Addition of sodium nitrite (NaNO2), which is thought to be a one-electron donor, to the stoichiometric reaction mixture of 1 and H2O2 increased the initial formation rate of 2. The presence of uric acid (UA) caused a significant delay in the formation of 2. The delay of the appearance of 2 was directly proportional to the starting concentration, [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, [FeIVO(TMPyP•)]5+ (3), as a compulsory intermediate in the rate-determining step of the overall reaction, 1 + H2O2→ 2, with a rate constant k = 4.4 × 104 M−1.s−1. The rate constants for the reaction between 2 and NaNO2, and between 2 and UA were estimated to be 9.0 M−1s−1 and 5.45 × 106M−1.s−1, respectively.