Synthesis and Blood Glucose Lowering Activity of Novel Benzenesulfonyl-Urea Derivatives

Treatment of the pyridazinone derivatives ( 1a, 1b ) with ethyl chloroformate afforded novel carbamates ( 2a, 2b ). Subsequent treatment of 2a, 2b with appropriate amines gave novel benzenesulfonylurea derivatives ( 3a–i ). All these compounds were characterized on the basis of ¹ H NMR, IR, Mass spectral data and elemental analysis results. Preliminary biological testing of urea derivatives revealed that some compounds possess significant blood sugar lowering activity. Four compounds ( 3c, 3f, 3g , and 3h ) were found to have promising blood glucose lowering activity and may be used as lead compounds for developing new antidiabetic drugs.     

Tripodal Cadmium Complex and Macrocyclic Ligand Based Sensors for Phosphate Ion Determination in Environmental Samples

Tripodal cadmium complex of hydrotris(3‐phenyl‐5‐methylpyrazolyl)borate (I₁) and macrocyclic ligand 5,7 : 12,14 : 19,21 : 26,28‐Bzo₄‐[28]‐5,13,19,27‐tetraene‐8,11,22,25‐N_4–1,4,15,18‐O₄ (I₂), have been synthesized and characterized by IR, ¹H NMR, Mass and elemental analysis. Spectroscopic investigations indicate high affinity of these receptors for dihydrogen phosphate ion. Polyvinyl chloride (PVC) based membranes of (I₁) and (I₂) using hexadecyl trimethylammonium bromide (HTAB) as cation discriminator and dibutylpthalate (DBP), tributyl phosphate (TBP), dioctylsebacate (DOS), and o‐nitrophenyloctyl ether (o‐NPOE), as plasticizing solvent mediators were prepared and investigated as H₂PO selective sensors. The best performance was shown by the membrane of composition (w/w) (I₂) (5%):PVC (31%) : DBP (61.5%):HTAB (2.5%). This sensor works well over a wide concentration range 2.1×10^?7 to 1.0×10^?2 M with Nernstian compliance (59.0 mV decade^?1 of activity) with a fast response time of 14 s and showed good selectivity for dihydrogen phosphate ion over a number of anions. The sensor exhibits good reproducibility (SD±0.3 mV) and could be used successfully for the determination of phosphate in soil water samples.     

Evaluation of the binding of oxovanadium(IV) to human serum albumin

The understanding of the biotransformations of insulin mimetic vanadium complexes in human blood and its transport to target cells is an essential issue in the development of more effective drugs. We present the study of the interaction of oxovanadium(iv) with human serum albumin (HSA) by electron paramagnetic resonance (EPR), circular dichroism (CD) and visible absorption spectroscopy. Metal competition studies were done using Cu(II) and Zn(II) as metal probes. The results show that V(IV)O occupies two types of binding sites in albumin, which compete not only with each other, but also with hydrolysis of the metal ion. In one of the sites the resulting V(IV)O-HSA complex has a weak visible CD signal and its X-band EPR spectrum may be easily measured. This was assigned to amino acid side chains of the ATCUN site. The other binding site shows stronger signals in the CD in the visible range, but has a hardly measurable EPR signal; it is assigned to the multi metal binding site (MBS) of HSA. Studies with fatted and defatted albumin show the complexity of the system since conformational changes, induced by the binding of fatty acids, decrease the ability of V(IV)O to bind albumin. The possibility and importance of ternary complex formation between V(IV)O, HSA and several drug candidates - maltol (mal), picolinic acid (pic), 2-hydroxypyridine-N-oxide (hpno) and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone (dhp) was also evaluated. In the presence of maltol the CD and EPR spectra significantly change, indicating the formation of ternary VO-HSA-maltol complexes. Modeling studies with amino acids and peptides were used to propose binding modes. Based on quantitative RT EPR measurements and CD data, it was concluded that in the systems with mal, pic, hpno, and dhp (V(IV)OL(2))(n)(HSA) species form, where the maximum value for n is at least 6 (mal, pic). The degree of formation of the ternary species, corresponding to the reaction V(IV)OL(2) + HSA -->/<-- V(IV)OL(2)(HSA) is hpno > pic ≥ mal > dhp. (V(IV)OL)(n)(HSA) type complexes are detected exclusively with pic. Based on the spectroscopic studies we propose that in the (V(IV)OL(2))(n)(HSA) species the protein bounds to vanadium through the histidine side chains.     

Spectroscopic investigation of interaction of 6-methoxyflavanone and its β-cyclodextrin inclusion complex with calf thymus DNA

The interaction of 6-methoxyflavanone (6MF, 6-methoxy-2-phenyl-4H-1-benzopyran-4-one) with calf thymus DNA (ctDNA) was investigated by absorption spectroscopy, fluorescence spectroscopy, and cyclic voltammetry in the presence and absence of ??-cyclodextrin (??-CD) acting as capping agent. Molecular modelling was used to optimise the study of 6MF-??-CD and 6MF-DNA interactions. Enhancement in the fluorescence intensity of 6MF was observed due to the formation of 1 : 1 complex with ??-CD. In the presence and absence of DNA, 6MF showed different characteristics such as hyperchromic effect, red shift of absorption spectra and fluorescence quenching of 6MF due to binding between 6MF and ctDNA. The nature of the binding group was found to be different for the 6MF-ctDNA and 6MF-ctDNA-??-CD systems. An increase in fluorescence intensity was observed for the 6MF-ctDNA system while varying the concentration of ??-CD due to encapsulation of a part of 6MF in cyclodextrin. The results are compatible with the possibility of the interaction of dihydrobenzopyran-4-one moiety of 6MF with ctDNA as well as with ??-CD. Cyclic voltammetric studies confirmed the binding interaction between 6MF and ctDNA in the absence and presence of ??-CD and molecular modelling explains the site of the interaction of 6MF with cyclodextrin and ctDNA.     

Cobalt(II)-selective membrane sensor based on a [Me2(13)dieneN4] macrocyclic cobalt complex

A new poly(vinyl chloride)-based membrane was fabricated with the cobalt(II) complex of 2,4-dimethyl-1,5,8,11-tetraazacyclotrideca-1,4-diene [Me₂(13)dieneN₄] as an ion carrier. The membrane composition was Co²⁺ complex/PVC/NaTPB/DBP 15:50:15:20 (w/w). The sensor exhibited a Nernstian response for Co²⁺ ions over a wide concentration range (7.94×10⁻⁶–1.0×10⁻¹ M) at pH 2.5–7.0, a response time of 10 s, and it could be used for 3 months without any significant divergence in potential. The proposed membrane sensor exhibited good selectivity for Co²⁺ over a wide variety of other metal ions and in mixtures containing up to 25% (v/v) non-aqueous content. The sensor was successfully used as an indicator electrode in the potentiometric titration of Co²⁺ with EDTA and the direct determination of Co²⁺ in real samples.     

Icosahedral DNA Nanocapsules by Modular Assembly

It's a trap! DNA polyhedra formed through molecular self‐assembly may function as nanocapsules for the targeted delivery of encapsulated entities. This functional aspect was demonstrated for the most complex DNA‐based platonic solid: During the stepwise amalgamation of discrete polyhedra to form icosahedra, gold nanoparticles (GNPs) were encapsulated from solution (see illustration and TEM image of icosahedral cages containing GNPs).