Selective and sensitive turn on fluorescence cyanide recognition in aqueous medium based on Zn(II)-hydrazone metal complex chemosensor.

Detection and quantification of the cyanide ion (CN- ) has attracted considerable attention because of its extreme toxicity. A novel Zn(II)-complex, applicable as a fluorescent chemosensor for CN- recognition, was synthesized in excellent yields from the reaction of zinc sulfate with the novel hydrazone: 3-(amino-9H-purin-yl)-N'-(hydroxybenzylidene) propanehydrazide. The structures of the hydrazone (L) and the zinc-hydrazone complex (L.Zn) were characterized by ultraviolet-visible spectrophotometry, Fourier-transform infrared spectrometry, mass spectrometry, proton- and carbon-13-nuclear magnetic resonance. The sensing performance of the proposed chemosensors, L and L.Zn, towards common ions was investigated via naked-eye studies as well as absorption and emission spectral analysis. Hydrazone (L) efficiently functioned as a fluorescence sensor for aluminum ions (Al3+ ) and zinc ions (Zn2+ ) with large binding constants, and exhibited colorimetric and fluorometric responses for several basic anions: OH- , CO3 2- , HCO3 - , HSO3 - , CH3 COO- and CN- . However, L.Zn showed quick, sensitive and specific enhancement of fluorescence intensity towards CN- anion, and a linear relationship was observed as the concentration of CN- varied from 1 to 14 µM. The detection limit was determined to be 0.14 µM, which is lower than the 1.9 µM maximum value recommended by the World Health Organization for drinking water. The practical performance of the sensor was successfully demonstrated using various environmental water samples spiked with cyanide ion.

Novel triazine-based pyrimidines suppress glomerular mesangial cells proliferation and matrix protein accumulation through a ROS-dependent mechanism in the diabetic milieu.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes worldwide. It is depicted as the leading cause of end-stage renal disease. Oxidative stress plays a key role in hyperglycemia-induced DN. The preparation and characterization of novel mono-, di-, and trisubstituted-s-triazines endowed with uracil and/or thymine are described in this paper. The synthesis of the title compounds was realized through selective nucleophilic substitution reactions of cyanuric chloride with the corresponding hydrazide nucleobases. In this study, we assessed the effects of these derivatives on the progression of diabetic nephropathy. Our results show that trisubstituted-s-triazines endowed with acylhydrazides attenuate high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro. Notably, these derivatives also display anti-oxidative properties. This suggests that the novel trisubstituted-s-triazine derivatives provide renal protection through a reactive oxygen species (ROS)-dependent mechanism. Our data provide evidence that these derivatives may serve as potential therapeutic candidates in the treatment of DN.

Spectroscopic Evaluation of Novel Adenine/Thymine-Conjugated Naphthalenediimides: Preference of Adenine-Adenine over Thymine-Thymine Intermolecular Hydrogen Bonding in Adenine- and Thymine-Functionalized Naphthalenediimides.

The synthesis and spectroscopic characterization of novel nucleobase (adenine/thymine)-conjugated naphthalenediimides (NDIs), namely, NDI-AA, NDI-TT, and NDI-AT have been successfully achieved. NDI-AA, NDI-TT and NDI-AT have similar absorption in the 300-400 nm region. The effect of solvent on the absorption spectrum indicates aggregation, either through intermolecular π-σ interaction among the main chromophore or through intermolecular hydrogen bonding between adenine and adenine group. Addition of water does not assist hydrogen bond formation between thymine-thymine, rather increasing the polarity of the solvent encourages π-σ interaction among NDI-TTs. No spectral change for NDI-TT with increasing temperature confirms hydrogen bonding is not playing a crucial role in NDI-TT. A fluorescence study on NDI-AA also establishes excimer formation along with ground state aggregation. As the water content in the solvent mixture increases, aggregation of NDI-AA is discouraged due to adenine-adenine hydrogen bonding in accordance with earlier results. At the same time, the NDI-TT emission spectrum does not shift to the blue region and the intensity of the peak around 535 nm increases at the expense of fluorescence in 411 nm. Thus, increasing water content in the solvent mixture facilitates aggregation through π-σ interaction in NDI-TT as thymine-thymine hydrogen bonding is less pronounced.

Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu. II. Acylhydrazone-functionalized pyrimidines.

We report herein the synthesis of a novel series of carbocyclic acylhydrazone derivatives of uracil, thymine and cytosine from the corresponding nucleic bases and their biological activity to treat diabetic nephropathy. Intriguingly, five derivatives significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro. The anti-oxidative effects displayed by these molecules suggest that their activity might involve a ROS-dependent mechanism.

Novel carbocyclic nucleoside analogs suppress glomerular mesangial cells proliferation and matrix protein accumulation through ROS-dependent mechanism in the diabetic milieu.

The synthesis of a series of novel 3,4-cis- and 3,4-trans-substituted carbocyclic nucleoside analogs from protected uracil and thymine is described. The key reaction in the followed synthetic protocols utilized the Mitsunobu reaction to couple 3,4-substituted cyclopentanols to (3)N-benzoyl uracil or (3)N-benzoyl thymine. These molecules were evaluated with regard to their ability to treat diabetic nephropathy. Our results show that two analogs significantly reduced high-glucose induced glomerular mesangial cells proliferation and matrix protein accumulation in vitro and, more interestingly, exhibited an anti-oxidative effect suggesting that the activity may be mediated through ROS-dependent mechanism.

Synthesis, cyclopolymerization and cyclo-copolymerization of 9-(2-diallylaminoethyl)adenine and its hydrochloride salt.

We report herein the synthesis and characterization of 9-(2-diallylaminoethyl) adenine. We evaluated two different synthetic routes starting with adenine where the optimal route was achieved through coupling of 9-(2-chloroethyl)adenine with diallylamine. The cyclopolymerization and cyclo-copolymerization of 9-(2-diallylaminoethyl)adenine hydrochloride salt resulted in low molecular weight oligomers in low yields. In contrast, 9-(2-diallylaminoethyl)adenine failed to cyclopolymerize, however, it formed a copolymer with SO2 in relatively good yields. The molecular weights of the cyclopolymers were around 1,700-6,000 g/mol, as estimated by SEC. The cyclo-copolymer was stable up to 226 °C. To the best of our knowledge, this is the first example of a free-radical cyclo-copolymerization of a neutral alkyldiallylamine derivative with SO2. These polymers represent a novel class of carbocyclic polynucleotides.

Facile preparation of the tosylhydrazone derivatives of a series of racemic trans-3,4-substituted cyclopentanones.

We report the synthesis and characterization of a variety of trans-3,4-substituted cyclopentanones and the corresponding tosylhydrazone derivatives starting with diethyl fumarate. Protection of the keto group followed by selective monohydrolysis of esters was achieved, resulting in cyclopentanones with different substituents at positions 3 and 4. The tosylhydrazone derivative of each cyclopentanone intermediate was prepared in moderate to good yields. These compounds are potential precursors for functionalized methanofullerenes.

Synthesis and polymerization of 1-(2-diallylaminoethyl)pyrimidines.

We report the preparation and characterization of three pyrimidine-based monomers, specifically: 1-(2-diallylaminoethyl)uracil, 1-(2-diallylaminoethyl)thymine and 1-(2-diallylaminoethyl)cytosine. Monomer synthesis was initiated by reaction of the pyrimidine with ethylene carbonate to form the hydroxyethyl adduct which was subsequently chlorinated to afford the chloroethyl intermediate. Reaction of the chloroethyl derivatives with diallylamine resulted in the desired monomers. We demonstrated a two-fold increase in the overall yield of the three monomers in comparison to reported procedures. The cyclopolymerization and cyclo-copolymerization of 1-(2-diallylaminoethyl)pyrimidine trifluoroacetate salts in water resulted in low-yield homopolymers. In contrast, the neutral 1-(2-diallylaminoethyl)pyrimidines cyclo-copolymerized with sulfur dioxide and V-50 initiator to yield the corresponding copolymers in higher yields ranging from 30 to 60%.

Interactions of Some Divalent Metal Ions with Thymine and Uracil Thiosemicarbazide Derivatives.

The study of interactions between metal ions and nucleobases, nucleosides, nucleotides, or nucleic acids has become an active research area in chemical, biological, and therapeutic fields. In this respect, the coordination behavior of nucleobase derivatives to transition metals was studied in order to get a better understanding about DNA-metal interactions in in vitro and in vivo systems. Two nucleobase derivatives, 3-benzoyl-1-[3-(thymine-1-yl)propamido]thiourea and 3-benzoyl-1-[3-(uracil-1-yl)propamido]thiourea, were synthesized and their dissociation constants were determined at different temperatures and 0.3 ionic strength. Potentiometric studies were carried out on the interaction of the derivatives towards some divalent metals in 50% v/v ethanol-water containing 0.3 mol.dm(-3) KCl, at five different temperatures. The formation constants of the metal complexes for both ligands follow the order: Cu(2+) > Ni(2+) > Co(2+) > Zn(2+) > Pb(2+) > Cd(2+) > Mn(2+). The thermodynamic parameters were estimated; the complexation process has been found to be spontaneous, exothermic, and entropically favorable.

Poly (9-(2-diallylaminoethyl)adenine HCl-co-sulfur dioxide) deposited on silica nanoparticles constructs hierarchically ordered nanocapsules: curcumin conjugated nanocapsules as a novel strategy to amplify guanine selectivity among nucleobases.

Poly (9-(2-diallylaminoethyl)adenine HCl-co-sulfur dioxide) (Poly A) deposited on silica nanoparticles self-assembles to form hierarchically ordered nanocapsules. These nanocapsules can be conjugated with curcumin. The curcumin-conjugated nanocapsules are found to be spherical in size and their size ranges between 200 and 600 nm. We found that curcumin conjugated with silica nanoparticles marginally shows a selectivity (∼20%) for guanine over adenine, cytosine, thymine and uracil, but this selectivity is extraordinarily amplified to more than 500% in curcumin-conjugated nanocapsules prepared from the above procedure. FT-IR spectra along with lifetime measurements suggest that specific interaction between adenine moieties of Poly A nanocapsules and thymine/uracil does not affect the fluorescence of poly A nanocapsules. Thus, the sensitivity and selectivity for guanine estimation is due to hydrophobic interactions, which are assisted by the low water solubility of guanine as compared to the other nucleobases. The present method illustrates a wider linear dynamic range in the higher concentration range as compared to the reported methods. Finally, the degradation study proves that stability of curcumin is improved dramatically in such nanocapsules demonstrating that nanotechnology could be a viable method to improve selectivity of specific analyte and robustness of probe molecule during fluorescence based bio-sensing.

Thiophene aldehyde-diamino uracil Schiff base: A novel fluorescent probe for detection and quantification of cupric, silver and ferric ions.

A new Schiff base from the condensation of 5,6-diamino-1,3-dimethyluracil with 5-methylthiophene-2-carboxaldehyde was synthesized. The compound was characterized by spectral data (UV-Vis, IR, (1)H NMR, fluorescence, MS). Ethanolic solutions of the Schiff base exhibit a strong fluorescence emission at 385 nm (λex=341 nm), and have been employed as a "turn-off" fluorescent probe for selective detection of Ag(+), Cu(2+) and Fe(3+) ions in presence of other cations such as Na(+), K(+), Ca(2+) and Mg(2+) ions abundant in natural water. The interaction between the tested compound and copper, silver or iron ions is associated with a significant fluorescence decrease, showing detection limits of 2.1-14.2 ppb. Under optimal conditions, the developed sensor was successfully employed to determine Ag(+), Cu(2+) and Fe(3+) ions in real samples and proved to be selective and sensitive.

Controlled degradation of hydrogels using multi-functional cross-linking molecules.

Hydrogels, chemically cross-linked or physically entangled, have found a number of applications as novel delivery vehicles of drugs and cells. However, the narrow ranges of degradation rates and mechanical strength currently available from many hydrogels limits their applications. We have hypothesized that utilization of multi-functional cross-linking molecules to form hydrogels could provide a wider range and tighter control over the degradation rates and mechanical stiffness of gels than bi-functional cross-linking molecules. To address the possibility, we isolated alpha-L-guluronate residues of sodium alginate, and oxidized them to prepare poly(aldehyde guluronate) (PAG). Hydrogels were formed with either poly(acrylamide-co-hydrazide) (PAH) as a multi-functional cross-linking molecule or adipic acid dihydrazide (AAD) as a bi-functional cross-linking molecule. The initial properties and degradation behavior of both PAG gel types were monitored. PAG/PAH hydrogels showed higher mechanical stiffness before degradation and degraded more slowly than PAG/AAD gels, at the same concentration of cross-linking functional groups. The enhanced mechanical stiffness and prolonged degradation behavior could be attributed to the multiple attachment points of PAH in the gel at the same concentration of functional groups. This approach to regulating gel properties with multifunctional cross-linking molecules could be broadly used in hydrogels.

Photocrosslinked alginate hydrogels with tunable biodegradation rates and mechanical properties.

Photocrosslinked and biodegradable alginate hydrogels were engineered for biomedical applications. Photocrosslinkable alginate macromers were prepared by reacting sodium alginate and 2-aminoethyl methacrylate in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride and N-hydroxysuccinimide. Methacrylated alginates were photocrosslinked using ultraviolet light with 0.05% photoinitiator. The swelling behavior, elastic moduli, and degradation rates of photocrosslinked alginate hydrogels were quantified and could be controlled by varying the degree of alginate methacrylation. The methacrylated alginate macromer and photocrosslinked alginate hydrogels exhibited low cytotoxicity when cultured with primary bovine chondrocytes. In addition, chondrocytes encapsulated in these hydrogels remained viable and metabolically active as demonstrated by Live/Dead cell staining and MTS assay. These photocrosslinked alginate hydrogels, with tailorable mechanical properties and degradation rates, may find great utility as therapeutic materials in regenerative medicine and bioactive factor delivery.

Evaluation of chain stiffness of partially oxidized polyguluronate.

The chain stiffness of macromolecules is considered critical in their design and applications. This study utilizes polyguluronate derived from alginate, a typical polysaccharide widely utilized in many biomedical applications, as a model macromolecule to investigate how the chain stiffness can be tightly regulated by partial oxidation. Alginate has a backbone of inherently rigid alpha-L-guluronate (i.e., polyguluronate) and more flexible beta-D-mannuronate. The chain stiffness of the polyguluronate was specifically studied in this paper, as this component plays a critical role in the formation of alginate hydrogels with divalent cations and is the dominant factor in determining the chain stiffness of alginate. We have utilized size-exclusion chromatography, equipped with refractive index, viscosity, and light-scattering detectors, to determine the intrinsic viscosity and the weight-average molecular weight of each fraction of samples. The chain stiffness of partially oxidized polyguluronate was then evaluated from the exponent of the Mark-Houwink equation and the persistence length. We have found that partial oxidation can be used to tightly regulate the steric hindrance and stiffness of the polyguluronate backbone. This approach to control the chain stiffness of inherently rigid polysaccharides by partial oxidation may find many applications in biomedical utilization of these materials.