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Biomedical subjects

Santanu Bhattacharya

Publications and source records attributed to Santanu Bhattacharya.

At least 19 recordsLinked to original sources
PubMed2006

Dendron-like growth of silver nanoparticles using a water-soluble oligopeptide.

A dendron-like nanostructure of silver was grown in solution using a water-soluble tetrapeptide Tyr-Aib-Tyr-Val (Aib, alpha-amino isobutyric acid), silver nitrate, and methanol. These structures are composed of silver nanoparticles having a bimodal size distribution with the median diameters around 2.0 and 19.5 nm, respectively. The dendron-like growth is ascribed to the effect of the local electric field generated by the dipoles associated with the peptide molecules. The optical absorption spectra have been analyzed by Mie scattering theory, which shows that there is a metal-nonmetal transition in silver particles having diameters less than approximately 2.0 nm.

Dendrimers↗
PubMed2005

Effect of heteroatom insertion at the side chain of 5-alkyl-1H-tetrazoles on their properties as catalysts for ester hydrolysis at neutral pH.

[reaction: see text] Herein we introduce tetrazole and its suitably designed derivatives as powerful ester-cleaving reagents. By first performing a detailed ab initio computational study, we found that, in the side chain of 5-alkyl-1H-tetrazoles, introduction of a heteroatom (e.g., N, O, or S at the alpha-position of the tetrazole ring) raises the charge on the tetrazole nucleus significantly. All calculations have been performed using restricted Hartree-Fock (RHF) and hybrid ab initio/DFT (B3LYP) methods employing 6-31G* and 6-31+G* basis sets. To estimate the nucleophilicity of these reagents, the charges on conjugate bases of various tetrazole derivatives have been calculated using natural population (NBO) analysis in gas phase and in water. Free energy of protonation (fep) of the 1H-tetrazole derivatives (1-7), free energy of solvation, deltaG(aq), and the corresponding pKa values have been calculated by self-consistent reaction field (SCRF) methods applying the polarized continuum model (PCM). Since the calculation indicates that incorporation of heteroatom leads to enhanced nucleophilicity in their deprotonated anionic tetrazole forms, a series of 5-substituted 1H-tetrazole derivatives have been synthesized. These compounds indeed catalyze the hydrolysis of p-nitrophenyl diphenyl phosphate (PNPDPP) and p-nitrophenyl hexanoate (PNPH) efficiently in cationic cetyl trimethylammonium bromide (CTABr) micelles at pH 7.0 and 25 degrees C. The pseudo-first-order rate constants (k(obs)) were determined for each catalyst against both substrates. The experimental and theoretical results show that, to achieve better k(obs) values for the cleavage of PNPDPP and PNPH under micellar conditions, charge on the N- atom (nucleophile) of conjugate base is important. Replacing the alpha-CH2 in alkyl substituent with S (3), NH (4), or O (5) enhances the accumulation of charge on N- in conjugate bases of tetrazoles and subsequently increases their intrinsic nucleophilic reactivity toward hydrolytic reactions. Significantly large rate enhancements were observed for the cleavage of PNPDPP and PNPH at pH 7.0 in the presence of catalytic system 5/CTABr over background (only CTABr). Tetrazole 4 (alpha-isomer) showed 4-5-fold superior reactivity over 6 (beta-isomer) under identical conditions. Natural charges obtained from NBO analysis (B3LYP/6-31+G*) are -0.94 and -0.852 on N- in the conjugate bases of 4 and 6, respectively. This also predicts that 4 is a better nucleophile than 6. All the newly synthesized tetrazole derivatives in micellar media display true catalytic properties by cleaving several fold excess of substrates.

Catalysis↗
PubMed2005

Recent advances in lipid molecular design.

The area of lipid molecular design is attracting widespread interest among numerous research groups worldwide. Diverse lipid assemblies in aqueous media, such as vesicles, bilayers and nanorods, offer new applications in chemical biology. Lipids with specifically tailored molecular architecture have been successfully employed as gene delivery vehicles, for controlled drug release and the preparation of supramolecular gels. Such molecular design of lipids, as well as their characterization upon membrane formation, offers an insight into the possible molecular basis of their properties. This in turn helps in the design of further generations of lipid systems with more predictable characteristics. Here, we present an overview of the current trends in lipid design and their utilization in various biochemical, physical and chemical applications.

Cell Membrane Permeability↗
PubMed2005

A tetrameric sugar-based azobenzene that gels water at various pH values and in the presence of salts.

A novel low-molecular mass tetrameric sugar derivative containing azobenzene core, 1, showed pronounced hydrogelation at micromolar concentration. Based on this observation, four related azobenzene based tetrameric sugar derivatives, 4-7, and three tetrameric sugar derivatives with a bis-terephthalamide core, 9-11, were also synthesized. However, none of these closely related analogues of the compound 1 showed effective gelation. The gel formed from 1 was characterized extensively using melting temperature analysis, UV-vis, FT-IR, circular dichroism spectroscopy, and scanning electron microscopy. The resultant gel exhibited impressive tolerance to the pH variation of the aqueous phase and gelated water in the pH range of 4-10. While UV-vis and CD spectroscopy indicated that pronounced aggregation of the azobenzene chromophores in 1 was responsible for gelation, FT-IR studies showed that hydrogen bonding is also a contributing factor in the gelation process. The melting of gel was found to depend on the pH of the aqueous medium in which gel was formed. The gel showed considerable photostability to UV irradiation, indicating tight intermolecular packing inside the gelated state that rendered azobenzene groups in the resultant aggregate refractory to photoisomerization. The electron micrographs of the aqueous gels of 1 showed the existence of spongy globular aggregates in such gelated materials. Addition of salts to the aqueous medium led to a delay in the gelation process and also caused remarkable morphological changes in the microstructure of the gel.

Journal Article↗
PubMed2005

Microcalorimetric and conductivity studies with micelles prepared from multi-headed pyridinium surfactants.

A set of novel single-chain surfactants bearing one (P1), two (P2), and three (P3) pyridinium headgroups have been synthesized in an attempt to achieve control over the aggregate properties. The critical micellar concentrations (cmc's) and the degrees of counterion dissociation (alpha) of micelles of these surfactants were determined by conductometry. The cmc and the alpha values increased with increase in the number of headgroups of the surfactant. The thermodynamics of micellization of these surfactants were investigated by microcalorimetry, and the results were compared with that of well-known single-chain/single-headgroup surfactant, cetylpyridinium bromide (CPB). The relationship between the cmc of surfactant in solution and its free energy of micellization (deltaG(o)m) was derived for each surfactant. Exothermic enthalpies of micellization (deltaH(o)m) and positive entropies of micellization (deltaS(o)m) were observed for all the surfactants. deltaH(o)m values were found to be more negative for CPB than P1, and it increased with a negative sign from P1 to P2 and decreased for P3. In contrast the deltaS(o)m values decreased with increase in the number of headgroups. The deltaG(o)m values progressively became less negative with increase in the number of headgroups. This implies that micelle formation becomes less favorable as more headgroups are incorporated in the surfactant.

Journal Article↗
PubMed2005

Synthesis and antibacterial properties of novel hydrolyzable cationic amphiphiles. Incorporation of multiple head groups leads to impressive antibacterial activity.

Two sets of novel multiheaded cationic amphiphiles bearing one, two, and three trimethylammonium headgroups (T1, T2, and T3) and pyridinium headgroups (P1, P2, and P3), have been synthesized and tested for antimicrobial activities against both Gram-positive and Gram-negative bacteria. The multicationic headgroups in these amphiphiles were attached covalently via scissile ester-type linkages. The results were compared with those for known surface-active, nonhydrolyzable compounds cetyltrimethylammonium bromide (CTAB) and cetylpyridinium bromide (CPB). The killing effects of the new single-headed amphiphiles (T1 and P1) were lower than those of CTAB and CPB, but with an increase in the number of headgroups in the amphiphiles, the killing effects increased for both sets of compounds. It was found that amphiphiles with triple headgroups (T3 and P3) were most active among all the amphiphiles, whereas amphiphile P1 had a very poor killing effect on both types of bacteria. The multiheaded pyridinium amphiphiles were more active compared to their trimethylammonium counterparts. The time needed to kill bacteria with multiheaded amphiphiles was significantly less than that of single-headed amphiphiles. Owing to the presence of a cleavable ester moiety, these new amphiphiles are hydrolyzed spontaneously at physiological conditions. This property enables them to be readily metabolized and therefore have the potential to be superior disinfectants and antiseptics for food and body surfaces.

Anti-Bacterial Agents↗
PubMed2005

Unusual micellar properties of multiheaded cationic surfactants in the presence of strong charge neutralizing salts.

The aggregation properties of single-chain surfactants bearing one (H1), two (H2), and three (H3) trimethylammonium head groups have been studied by small-angle neutron scattering (SANS). Growth of aggregates was observed to decrease dramatically with an increase in the number of head groups in the surfactants. The micelles grow progressively smaller with every increase in the number of head groups of the surfactants. Aggregation number (N) continuously decreases and the fractional charge (alpha) gradually increases with the increase in the number of head groups. The semiminor axis (a) and semimajor axis (b=c) of the micelle decrease strongly with the increase in the number of head groups. In the case of H1, dramatic micellar growth is observed on addition of salts such as KBr and sodium salicylate, but this type of micellar growth is not observed in the cases of H2 and H3 when the above salts are added to their micellar solutions. Aggregation number and size of the micelles remain almost the same, even after addition of KBr at a concentration as high as 100 mM. This observation with multiheaded cationic surfactants is unusual. Clearly, the charge density at the head group level of surfactants markedly influences their micellar aggregation properties.

Journal Article↗
PubMed2005

Ester cleavage properties of synthetic hydroxybenzotriazoles in cationic monovalent and gemini surfactant micelles.

Four new hydroxybenzotriazole derivatives have been synthesized. Two of them, N-tetradecyl-1-hydroxy-1H-benzo[d][1,2,3]triazole-6-carboxamide (2) and N-tetradecyl-1-hydroxy-1H-benzo[d][1,2,3]triazole-7-carboxamide (3), possess long alkyl chains, while the other two, 1-hydroxy-1H-benzo[d][1,2,3]triazole-6-carboxylic acid (4) and 1-hydroxy-1H-benzo[d][1,2,3]triazole-7-carboxylic acid (5), have carboxylate side chains. These compounds along with their parent unsubstituted 1-hydroxybenzotriazole (HOBt), 1, have been examined for the cleavage of p-nitrophenyl hexanoate (PNPH) and p-nitrophenyl diphenyl phosphate (PNPDPP) in comicelles with monovalent cetyltrimethylammonium bromide (CTABr) and the corresponding bis-cationic gemini surfactants 16-m-16, 2Br(-) of identical chain length at 25 degrees C and pH 8.2. The apparent pK(a) values of the HOBt derivatives in the comicelles of CTABr or 16-4-16 gemini surfactant have been determined from the rate versus pH profiles and were found to be comparable. Catalytic system 4/16-4-16 demonstrated over 2200- and 1650-fold rate enhancements in the hydrolysis of PNPDPP and PNPH, respectively, for identical reactions carried out at pH 8.2 and 25 degrees C in buffered aqueous media. The second-order rate constants for such bimolecular reactions were determined employing pseudophase micellar models. Experiments in which excess substrate was taken over HOBt derivatives demonstrated that the catalysts "turned over"; hydrolysis of the putative acylated or phosphorylated HOBt intermediates was rapid in either type of host micelles.

Journal Article↗
PubMed2004

Computational study on hydroxybenzotriazoles as reagents for ester hydrolysis.

1-Hydroxybenzotriazole (1) and several of its derivatives (2-5) demonstrate potent esterolytic activity toward activated esters such as p-nitrophenyl diphenyl phosphate (PNPDPP) and p-nitrophenyl hexanoate (PNPH) in cationic micelles at pH 8.2 and 25 degrees C. The deprotonated anionic forms of such reagents act as reactive species in the hydrolysis of ester. To rationalize the origin of their nucleophilic character, a detailed ab initio/DFT computational study has been performed on 1-5 along with additional hydroxybenzotriazole derivatives (6-13). The geometries of 1-hydroxybenzotriazoles (1-13) and their corresponding bases are discussed in detail. All calculations were carried out using different methods, i.e., restricted Hartree-Fock (RHF) and hybrid ab initio/DFT (B3LYP) using 6-31G and 6-31+G basis sets. Free energy of protonation ("fep") of the 1-hydroxybenzotriazoles (1-13), free energy of solvation DeltaG(aq), and the corresponding pK(a) values have been calculated. Solvation-free energies were calculated using density functional theory and the polarizable continuum model. In addition, to examine the reliability of calculated fep, benzaldehyde oxime (14) and 2-methyl propionaldehyde oxime (15) have been computed as reference systems using different methods and basis sets, the experimental feps of which are known. Our experimental finding shows that the compound 4 is the most effective catalyst for the hydrolytic cleavages of PNPDPP and PNPH. This has been predicted from our calculated fep, pK(a), and natural charge analysis results as well. In general, the introduction of electron-withdrawing substituents on 1-hydroxybenzotriazoles facilitates the lowering of pK(a) and fep. As the pK(a) values are lowered, a greater percentage of such hydroxybenzotriazoles remain in their deprotonated, anionic forms at pH 8.2. Since the anionic forms are nucleophilic, pK(a) lowering should enhance their ester cleaving capacity. However, such substitution also decreases the charge density on the catalytically active oxido atom (O(7)). Taking these two factors together, the derivatives are only modestly better nucleophiles in comparison to the parent 1-hydroxybenzotriazole. Interestingly, the introduction of electron-donating groups does not significantly enhance the charge accumulation on the oxido atom (O(7)) of 1-hydroxybenzotriazoles.

Computer Simulation↗
PubMed2004

Thermodynamics of micellization of multiheaded single-chain cationic surfactants.

The energetics of micelle formation of three single-chain cationic surfactants bearing single (h = 1), double (h = 2), and triple (h = 3) trimethylammonium [(+)N(CH(3))(3)] headgroups have been investigated by microcalorimetry. The results were compared with the microcalorimetric data obtained from well-known cationic surfactant, cetyl trimethylammonium bromide (CTAB), bearing a single chain and single headgroup. The critical micellar concentrations (cmc's) and the degrees of counterion dissociation (alpha) of micelles of these surfactants were also determined by conductometry. The cmc and the alpha values increased with the increase in the number of headgroups of the surfactant. The relationship between the cmc of the surfactant in solution and its free energy of micellization (DeltaG(m)) was derived for each surfactant. Exothermic enthalpies of micellization (DeltaH(m)) and positive entropies of micellization (DeltaS(m)) were observed for all the surfactants. Negative DeltaH(m) values increased from CTAB to h = 1 to h = 2 and decreased for h = 3 whereas DeltaS(m) values decreased with increase in the number of headgroups. The DeltaG(m) values progressively became less negative with the increase in the number of headgroups. This implies that micelle formation becomes progressively less favorable as more headgroups are incorporated in the surfactant. From the steady-state fluorescence measurements using pyrene as a probe, the micropolarities sensed by the probe inside various micelles were determined. These studies suggest that the micelles are more hydrated with multiheaded surfactants and the micropolarity of micelles increases with the increase in the number of headgroups.

Cations↗
PubMed2004

Evidence of enhanced reactivity of DAAP nucleophiles toward dephosphorylation and deacylation reactions in cationic gemini micellar media.

4,4'-(Dialkylamino)pyridine (DAAP)-based compounds 1-4 catalytically cleave hydrophobic organophosphate and carboxylate esters in various host micellar aggregates at mildly alkaline pH. The role of the micellar reaction medium in such esterolytic reactions has been carefully examined in this work. The cationic gemini surfactant based micellar aggregates provide more than 1 order of magnitude better reaction medium for the above reactions than their conventional single-chain, single-charge, cationic cetyl trimethylammonium bromide (CTABr) micelles. The catalytic turnover behavior of DAAP nucleophiles in the presence of excess substrates is also retained in gemini micellar media.

Journal Article↗
PubMed2003

Reactions that generate aromatic molecules: is aromatic stabilization less or more advanced than bond changes at the transition state? Kinetic and thermodynamic acidities of rhenium carbene complexes.

A kinetic study of the reversible deprotonation of the rhenium carbene complexes 1H(+)(O), 1H(+)(S) and 2H(+)(O) by carboxylate ions, primary aliphatic and secondary alicyclic amines, water and OH(-) in 50% MeCN-50% water (v/v) at 25 degrees C is reported. These carbene complexes are of special interest because in their deprotonated form they represent derivatives of the aromatic heterocycles furan, thiophene and benzofuran. Intrinsic rate constants (k(o) for Delta G degrees = 0) determined from appropriate Brønsted plots for these rhenium carbene complexes and for the corresponding selenophene (1H(+)(Se)) and benzothiophene (2H(+)(S)) derivatives investigated earlier follow the orders furan < selenophene < thiophene and benzofuran less, similar benzothiophene. These orders indicate that an increase in aromaticity leads to an increase in the intrinsic rate constant or a decrease in the intrinsic barrier. This is an unexpected result; it implies that, in contrast to common resonance effects, the development of aromaticity at the transition state is ahead of proton transfer, i.e., the percentage development of the aromatic stabilization energy at the transition state is higher than the percentage of proton transfer.

Journal Article↗
PubMed2003

A new ratiometric fluorescence probe as strong sensor of surface charge of lipid vesicles and micelles.

We report on the ability of a new fluorescent probe, 4-(2-pyren-1-yl-vinyl) pyridine, 1, to respond to micelles and phospholipid vesicles of different surface charge. The probe gets incorporated into micellar and membranous assemblies and shows a large red-shift in the fluorescence emission maxima especially when the surface charge of the organized media is anionic. The effect on the photo-excitation of the probe is very clear and pronounced as it can be easily visualized. The sample color upon photo-excitation changes from blue to orange/red once the probe experiences negatively charged vesicular or micellar surfaces. These results make the probe molecule useful as a reporter for sensing electrostatic environment in biological membranes and related organized assemblies.

Anions↗
PubMed2003

Synthesis of new Cu(II)-chelating ligand amphiphiles and their esterolytic properties in cationic micelles.

Four new tetradentate 2,6-disubstituted pyridine and tridentate 2-substituted pyridine ligands were synthesized. Two of these compounds possessed a metal ion binding subunit in the form of a 2,6-disubstituted-4-N,N'-dimethylamine pyridine moiety. Cu(2+)-complexes of these ligands incorporated in cetyltrimethylammonium bromide (CTABr) micelles speeded the cleavage of p-nitrophenyldiphenyl phosphate and p-nitrophenyl hexanoate at pH 7.6. On the basis of a kinetic version of Job plot analysis, a 1:1 ligand/Cu(2+) stoichiometry was found to be the most active species. In CTABr micelles, the pK(a) values for the Cu(2+)-coordinated hydroxyl or pendant -CH(2)OH in these ligands were between 7.8 and 7.9. The metallomicellar systems displayed catalytic (turnover) behavior in the presence of excess substrates.

Journal Article↗
PubMed2002

DNA binding properties of novel dansylated distamycin analogues in which the fluorophore is directly conjugated to the N-methyl-pyrrole.

Polyamides that are structural analogues of the naturally occurring DNA minor groove binding antibiotic distamycin (Dst) are promising candidates as gene modulators. Developing strategies for the large scale screening and monitoring of the cellular distribution of such ligands would aid the faster discovery of molecules, which would have eventual utility in molecular biology and medicine. Attachment of fluorescent tags would be a useful step towards this end. A fundamental question in this connection is whether the tag modifies the DNA binding affinity of the parent compounds. Towards answering this question, we have developed two oligopeptides that bear the dansyl (N, N-dimethylaminonaphthalene sulfonamido fluorophore) coupled directly to the N-terminus of the conjugated N-methylpyrrole carboxamide network, and possess three or four N-methyl pyrrole carboxamide units (abbreviated as Dn3 and Dn4 respectively). DNA binding abilities of these molecules were assessed from fluorescence titration experiments, duplex-DNA T(m) analysis (employing both UV and fluorescence spectroscopy), induced circular dichroism measurements (ICD), salt dependence of ICD and apparent binding constant measurements (K(app)) employing ethidium bromide (EtBr) displacement assay. Both these molecules reported DNA binding in the form of an enhanced fluorescence emission. As judged from the ICD measurements, salt dependence of ICD, T(m) analysis and K(app) measurements, the binding affinities of the molecules that possessed dansyl group at their N-termini were lower than the ones with equivalent number of amide units, but possessed N-methylpyrrole carboxamide unit at their N- termini. These results would have implications in the future design of fluorescent polyamides.

Antiviral Agents↗