The Preparation of Curcumin-Loaded Pickering Emulsion Using Gelatin-Chitosan Colloidal Particles as Emulsifier for Possible Application as a Bio-Inspired Cosmetic Formulation.

In the field of preparing cosmetic formulations, recent advances recommend the usage of excipients derived from biocompatible materials. In this context, the present study aimed to prepare and characterize the curcumin-loaded Pickering emulsion for possible applications in cosmetic formulation. The coconut oil which is often the component of skin care formulations is used as the oily phase. Curcumin, which is well known for absorbing solar radiation, is expected to work synergistically with coconut oil towards improving the sun protection factor (SPF) of the formulation. Additionally, curcumin can also protect the intracellular components through its well-known antioxidant mechanisms. The Pickering emulsion of coconut oil into water was prepared using the composite colloidal particles derived from ß-carboxymethyl chitosan (CMC) and Gelatin-A (GA) as the emulsifying agent. The reaction conditions in terms of the weight ratios of CMC and GA, the pH of the reaction medium, the oil volume fraction, and the homogenization speed were optimized to obtain the most stable Pickering emulsion. The obtained systems were physico-chemically characterized by dynamic light scattering, zeta potential, optical microscopy, and rheometric measurements. The final CMC-GA-stabilized emulsion demonstrated an oil droplet size of 100 µm and a SPFspectrophotometric (290-320 nm) value of 8.5 at a curcumin loading of 4 mg/mL. Additionally, the final formulation facilitated the uptake of curcumin into fibroblast (WI26) cells under in vitro conditions. Together, the investigation demonstrates a bio-inspired approach to prepare a curcumin-loaded green Pickering emulsion using biocompatible pharmaceutical grade excipients, which may find utility in cosmetic applications.

Repurposing of FDA approved kinase inhibitor bosutinib for mitigation of radiation induced damage via inhibition of JNK pathway.

Radiotherapy is a common modality for cancer treatment. However, it is often associated with normal tissue toxicity in 20-80% of the patients. Radioprotectors can improve the outcome of radiotherapy by selectively protecting normal cells against radiation toxicity. In the present study, compound libraries containing 54 kinase inhibitors and 80 FDA-approved drugs were screened for radioprotection of lymphocytes using high throughput cell analysis. A second-generation FDA-approved kinase inhibitor, bosutinib, was identified as a potential radioprotector for normal cells. The radioprotective efficacy of bosutinib was evinced from a reduction in radiation induced DNA damage, caspase-3 activation, DNA fragmentation and apoptosis. Oral administration of bosutinib protected mice against whole body irradiation (WBI) induced morbidity and mortality. Bosutinib also reduced radiation induced bone-marrow aplasia and hematopoietic damage in mice exposed to 4 Gy and 6 Gy dose of WBI. Mechanistic studies revealed that the radioprotective action of bosutinib involved interaction with cellular thiols and modulation of JNK pathway. The addition of glutathione and N-acetyl cysteine significantly reduced the radioprotective efficacy of bosutinib. Moreover, bosutinib did not protect cancer cells against radiation induced toxicity. On the contrary, bosutinib per se exhibited anticancer activity against human cancer cell lines. The results highlight possible use of bosutinib as a repurposable radioprotective agent for mitigation of radiation toxicity in cancer patients undergoing radiotherapy.

Biomass, carbon stock, CO2 mitigation and carbon credits of coffee-based multitier cropping model in Central India.

The present work was conducted in the forest-based ecosystem of Chhattisgarh in order to assess the varietal performance of coffee varieties along with silver oak in terms of growth, biomass, and carbon dynamics. Five coffee varieties were planted in silver oak shade in a randomized block design with four replications. The aim of the present investigation is to assess the economic and ecological feasibility of forest-based coffee plantations in the Bastar region of Chhattisgarh. Findings reflect the maximum under-storied plant height in Chandragiri Dwarf (1.85 m) which was at par with CxR (1.82 m) and San Ramon (1.71 m). The maximum above and below-ground carbon stock (48.40 and 12.09 Mg ha-1, respectively), as well as carbon dioxide (CO2) mitigation (177.63 and 44.41 Mg ha-1, respectively) from the under-storied coffee plantation, was recorded in CxR. In the upper-storied plantation, the above and below-ground biomass of silver oak recorded the maximum carbon stock (201.24 and 50.31 Mg ha-1, respectively) and CO2 mitigation (738.54 and 184.63 Mg ha-1) in S-8 intercropped lines. The highest value of carbon credit was recorded under the coffee variety S-8 and silver oak agroecosystem. The S-8, CxR, and Chandragiri Dwarf varieties performed quite well in terms of the expected value of carbon credit.

Malabaricone C, a constituent of spice Myristica malabarica, exhibits anti-inflammatory effects via modulation of cellular redox.

The present study primarily focuses on the efficacy of Malabaricone C (Mal C) as an anti-inflammatory agent. Mal C inhibited mitogen-induced T-cell proliferation and cytokine secretion. Mal C significantly reduced cellular thiols in lymphocytes. N-acetyl cysteine (NAC) restored cellular thiol levels and abrogated Mal C-mediated inhibition of T-cell proliferation and cytokine secretion. Physical interaction between Mal C and NAC was evinced from HPLC and spectral analysis. Mal C treatment significantly inhibited concanavalin A-induced phosphorylation of ERK/JNK and DNA binding of NF-κB. Administration of Mal C to mice suppressed T-cell proliferation and effector functions ex vivo. Mal C treatment did not alter the homeostatic proliferation of T-cells in vivo but completely abrogated acute graft-versus-host disease (GvHD)-associated morbidity and mortality. Our studies indicate probable use of Mal C for prophylaxis and treatment of immunological disorders caused due to hyper-activation of T-cells.

3,3'-Diselenodipropionic acid immobilised gelatin gel: a biomimic catalytic nitric oxide generating material for topical wound healing application.

Nitric oxide (NO) plays a pivotal role in the wound healing process and promotes the generation of healthy endothelium. In this work, a simple method has been developed for fabricating a diselenide grafted gelatin gel, which reduces NO donors such as S-nitroso-N-acetylpenicillamine (SNAP) by glutathione peroxidase-like mechanism to produce NO. Briefly, the process involved covalently conjugating 3,3'-diselenodipropionic acid (DSePA) with gelatin via carbodiimide coupling. The resulting gelatin-DSePA conjugate (G-Se-Se-G) demonstrated NO production upon incubation with SNAP and glutathione (GSH) with the flux of 4.8 ± 0.6 nmol cm-2 min-1 and 1.6 ± 0.1 nmol cm-2 min-1 at 10 min and 40 min, respectively. The G-Se-Se-G recovered even after 5 days of incubation with the reaction mixture retaining catalytic activity up to 74%. Subsequently, G-Se-Se-G was suspended (5% w/v) in water with lecithin (6% w/w of gelatin) and F127 (3% w/w of gelatin) to prepare gel through temperature dependant gelation method. The fabricated G-Se-Se-G gel exhibited desirable rheological characteristics and excellent mechanical stability under storage conditions and did not cause any significant toxicity in normal human keratinocytes (HaCaT) and fibroblast cells (WI38) up to 50 µg ml-1 of selenium equivalent. Finally, mice studies confirmed that topically applied G-Se-Se-G gel and SNAP promoted faster epithelization and collagen deposition at the wound site. In conclusion, the development of a biomimetic NO generating gel with sustained activity and biocompatibility was achieved.

Gelatin-lecithin-F127 gel mediated self-assembly of curcumin vesicles for enhanced wound healing.

Curcumin, a principal component of Curcuma longa, has a long history of being used topically for wound healing. However, poor aqueous solubility of curcumin leads to poor topical absorption. Recently, gelatin based gel has been reported to overcome this issue. However, the release of curcumin from gelatin gel in the bioavailable or easily absorbable form is still a challenge. The present study reports the development of a composite gel prepared from gelatin, F127 and lecithin using temperature dependant gelation and loading of curcumin within it. Notably, the composite gel facilitated the release of curcumin entrapped within vesicles of ~400 nm size. Further, the composite gel exhibited increase in the storage modulus or gel strength, stability, pore size and hydrophobicity as compared to only gelatin gel. Finally, wound healing assay in murine model indicated that curcumin delivered through composite gel showed a significantly faster healing as compared to that delivered through organic solvent. This was also validated by histopathological and biochemical analysis showing better epithelization and collagen synthesis in the group dressed with curcumin containing composite gel. In conclusion, composite gel facilitated the release of bioavailable or easily absorbable curcumin which in turn enhanced the wound healing.

Balancing loading, cellular uptake, and toxicity of gelatin-pluronic nanocomposite for drug delivery: Influence of HLB of pluronic.

In this study, pluronic stabilized gelatin nanocomposite of varying hydrophilic-lipophilic balance (HLB) were synthesized to study the effect of surface hydrophobicity on their cellular uptake and in turn the delivery of a model hydrophobic bioactive compound, curcumin (CUR). Notably, the variation in HLB from 22 to 8 did not cause much change in morphology (~spherical) and surface charge (~ -6.5 mV) while marginally reducing the size of nanocomposite from 165 ± 097 nm to 134 ± 074 nm. On contrary, nanocomposites exhibited a very significant increase in their numbers, hydrophobicity as well as CUR loading with decreasing HLB values (22-8) of pluronic. Further, the cellular uptake of CUR through pluronic-gelatin nanocomposites was studied in human lung carcinoma (A549) cells. The results indicated that cellular uptake of CUR through nanocomposites followed the order HLB 22 > HLB 18 > HLB 15 > HLB 8. This was also reflected in terms of the decrease in cytotoxicity of CUR through nanocomposite of HLB 8 as compared to that of HLB 22. Interestingly, bare nanocomposite of HLB 8 showed significantly higher cytotoxicity as compared to that of HLB 22. Together these results suggested that although higher hydrophobicity of the gelatin-pluronic nanocomposite facilitated higher entrapment of CUR, the carrier per se became toxic due to its hydrophobic interaction with lipid bilayer of plasma membrane. Thus, HLB parameter is very important in designing hybrid nanocomposite systems involving protein and pluronic to ensure both bio-compatibility of the carrier and the optimum cellular delivery of the pay load.

Functional and mechanistic insights into the differential effect of the toxicant 'Se(IV)' in the cyanobacterium Anabaena PCC 7120.

Selenium, an essential trace element for animals, poses a threat to all forms of life above a threshold concentration. The ubiquitously present cyanobacteria, a major photosynthetic biotic component of aquatic and other ecosystems, are excellent systems to study the effects of environmental toxicants. The molecular changes that led to beneficial or detrimental effects in response to different doses of selenium oxyanion Se(IV) were analyzed in the filamentous cyanobacterium Anabaena PCC 7120. This organism showed no inhibition in growth up to 15 mg/L sodium selenite, but above this dose i.e. 20-100 mg/L of Se(IV), both growth and photosynthesis were substantially inhibited. Along with the increased accumulation of non-protein thiols, a consistent reduction in levels of ROS was observed at 10 mg/mL dose of Se(IV). High dose of Se(IV) (above 20 mg/L) enhanced endogenous reactive oxygen species (ROS)/lipid peroxidation, and decreased photosynthetic capability. Treatment with 100 mg/L Se(IV) downregulated transcription of several photosynthesis pathways-related genes such as those encoding photosystem I and II proteins, phycobilisome rod-core linker protein, phycocyanobilin, phycoerythrocyanin-associated proteins etc. Interestingly, at a dose range of 10-15 mg/L Se(IV), Anabaena showed an increase in PSII photosynthetic yield and electron transport rate (at PSII), suggesting improved photosynthesis. Se was incorporated into the Anabaena cells, and Se-enriched thylakoid membranes showed higher redox conductivity than the thylakoid membranes from untreated cells. Overall, the data supports that modulation of photosynthetic machinery is one of the crucial mechanisms responsible for the dose-dependent contrasting effect of Se(IV) observed in Anabaena.

Redox reactions of organoselenium compounds: Implication in their biological activity.

Antioxidant activity of organoselenium compounds belonging to different classes i.e. functionalized aliphatic, aromatic and cyclic selenoethers, are compared on the basis of their ability to scavenge reactive oxygen species like hydroxyl and peroxyl radicals and to exhibit glutathione peroxidase (GPx) like catalytic activity. The comparative analysis has revealed that the antioxidant activity of the organoselenium compounds show direct correlation with the energy of the highest occupied molecular orbital (HOMO) and neighboring group participation that stabilizes the reaction intermediate. Finally, structural features responsible for improving the rate of reaction of organoselenium compounds with free radical/molecular oxidants have been discussed on the basis of the compounds screened at our institute.

Assessment of Correlation of Serum High-Sensitive C-Reactive Protein, Urinary Albumin-to-Creatinine Ratio, and Lipid Profile in Diabetics.

BACKGROUND: This study aimed to measure the level of serum high-sensitive C-reactive protein (hs CRP), urinary albumin-to-creatinine ratio (ACR), lipid profile, and their association in diabetics. METHODOLOGY: One hundred and fifty diabetic patients were classified into three groups of 50 each. Group I were newly diagnosed with <5 years of diabetes, Group II were those having 5-10 years of diabetes, and Group III were diabetics with more than 10 years of diabetes. Lipid profile, hs-CRP level, and ACR were measured. RESULTS: There was a correlation between hS CRP and ACR and triglyceride in Group I, hS CRP with ACR and triglyceride in Group I. In group II hS CRP showed significant correlation with ACR whereas in Group III significant correlation was observed with ACR, low density lipoprotein (LDL) and cholesterol. CONCLUSION: The level of hS CRP and ACR was found to be higher in patients with a longer duration of diabetes.

Assessment of Correlation of Oxidative Stress and Insulin Resistance with Glucose-6-Phosphate Dehydrogenase Activity in Type II Diabetes Mellitus Patients.

BACKGROUND: The present study aimed to assess the correlation of oxidative stress glucose-6-phosphate dehydrogenase (G6PD) activity in type II diabetes mellitus (DM) patients. METHODOLOGY: Forty-eight type II DM patients and healthy subjects were recruited. In all, G6PD activity, protein carbonyl, and total thiol levels were measured. RESULTS: The mean glycated hemoglobin (HbA1c) was 9.4% in Group I and 5.2% in Group II, G6PD activity was 6.5 U/gHb in Group I and 8.2 U/gHb in Group II, protein carbonyl was 14.2 nmol/mg protein in Group I and 3.5 nmol/mg protein in Group II, and total thiol level was 204.7 µmol/mL in Group I and 318.2 µmol/mL in Group II. In Group I, G6PD activity positively correlated with total thiol (r = 0.62) and negatively correlated with protein carbonyl (r = -0.73) and HbA1C (r = -0.67), protein carbonyl positively correlated with HbA1C (r =0.45) and negatively correlated with total thiol (r = -0.84), and total thiol negatively correlated with HbA1c (r = -0.30). CONCLUSION: G6PD may be considered a biomarker of oxidative stress and poor glycemic control in diabetic patients.

Preparation of a size selective nanocomposite through temperature assisted co-assembly of gelatin and pluronic F127 for passive targeting of doxorubicin.

The preparation of a water dispersible and pH responsive gelatin-F127 nanocomposite using a thermal relaxation approach is reported. The results indicated that physical properties (size and surface charge) of the gelatin-F127 nanoparticle can be tuned by varying the F127 to gelatin weight ratio. The heating (60 °C) of a saline solution (pH 7.4) containing 0.5% (w/v) of gelatin and 20% (w/w of gelatin) of F127 followed by gradual cooling at room temperature yielded nanoparticles of desired size (160 ± 40 nm), viscosity (1.36 ± cP) and surface charge (-6.47 ± 0.7 mV). The drug delivery application of nanocarriers was investigated using doxorubicin hydrochloride (Dox) as a model drug. These nanocarriers showed high encapsulation efficiency of Dox (85%), a sustained release profile, and substantial cellular internalization. Additionally, Dox loaded nanocarriers (G-Dox) exhibited prolonged residence in blood as evidenced by their longer circulation time as compared to plain Dox. Moreover, G-Dox exhibited a higher availability of the drug in plasma as compared to nonspecific organs such as the heart, liver and kidneys, highlighting its significance in reducing drug associated side effects. Finally, the enhanced toxicity of G-Dox to a WEHI-164 (fibrosarcoma) tumor model as compared to that of plain Dox under an identical dosage of 6 mg per kg body weight (IP) confirmed its potential for chemotherapy application.

Tuning the pharmacokinetics and efficacy of irinotecan (IRI) loaded gelatin nanoparticles through folate conjugation.

Gelatin based nanocarriers have major limitation of shorter circulation half-life (t1/2). Present study addressed this issue by conjugating gelatin with folate followed by nanoprecipitation in presence of polysorbate 80 to form folate attached gelatin nanoparticles (GNP-F). The folic acid was conjugated with gelatin through the formation of amide linkage with a maximum conjugation yield of ~69%. Cryo-SEM analysis indicated that unconjugated gelatin nanoparticles (GNP) and GNP-F were spherical of nearly identical size of ~200 nm. The irinotecan (IRI)-loading efficiency estimated for IRI-GNP and IRI-GNP-F was 6.6 ± 0.42% and 11.2 ± 0.73% respectively and both formulations showed faster release of IRI at acidic pH (~5) than at physiological pH (~7). Further IRI-GNP-F demonstrated significantly higher cytotoxicity in folate receptor (FR)-positive HeLa cells than the unconjugated IRI-GNP nanoparticles confirming active targeting. Subsequently the antitumor activity of above formulations in FR-positive fibrosarcoma (syngeneic) tumor-bearing mice followed the order of IRI-GNP-F > IRI-GNP > free IRI. The pharmacokinetic evaluation of IRI-GNP and IRI-GNP-F revealed that encapsulation of IRI within GNP without folate improved its plasma maximum concentration (Cmax). However, folate conjugation of GNP remarkably improved the t1/2 of IRI. Taken together, folate as a targeting ligand modulates the pharmacokinetic property of IRI loaded GNP to favor active verses passive targeting.

Gold Nanoparticle as a Lewis Catalyst for Water Elimination of Tyrosine-•OH Adducts: A Radiation and Quantum Chemical Study.

The role of gold nanoparticles (AuNPs) in the degradation of tyrosine intermediates formed during the radiation-induced •OH reaction with tyrosine at pH 6.5 is investigated by measuring the radiolytic yields, G, of tyrosine (-Tyr), dityrosine (DT), and 3,4 dihydroxyphenylalanine (DOPA). The G(DT) is doubled, whereas G(-Tyr) calculated is halved in the presence of 6.0 × 10-10 mol dm-3 AuNPs. Pulse radiolysis studies are carried out to elucidate the mechanism and nature of the transient formed in the reaction of •OH and •N3 with tyrosine. The formation of tyrosyl radical in the presence of AuNPs is found to be a major pathway through the decay of tyrosine-•OH adducts via the water elimination reaction, which is found to be 3× faster in the presence of AuNPs. Quantum chemical calculations on the system showed favorable formation of the tyrosine-AuNP complex. A new plausible mechanism of tyrosine-AuNP complex acting as a Lewis type catalyst in the decay of tyrosine-•OH adducts leading to reduced DOPA formation is proposed. The proposed mechanism is also complemented by the electronic spectra and energetics of the reaction of •OH with tyrosine using density functional theory calculations. Significantly, the H-shift reaction of ortho-tyrosine-•OH adducts is also found to be energetically viable. The investigation provides a new physical insight into the effect of AuNPs on the decay of free-radical transient species and demonstrates the potential of radiation chemical techniques and quantum chemical calculations as a tool for understanding the impact of metal nanoparticles in free-radical oxidation of amino acids, which is important in the use of metal nanoparticles for biomedical applications.

Nanodiamonds as a state-of-the-art material for enhancing the gamma radiation resistance properties of polymeric membranes.

We report, for the first time, the development of gamma radiation resistant polysulfone (Psf)-nanodiamond (ND) composite membranes with varying concentrations of NDs, ranging up to 2 wt% of Psf. Radiation stability of the synthesized membranes was tested up to a dose of 1000 kGy. To understand the structure-property correlationship of these membranes, multiple characterization techniques were used, including field-emission scanning electron microscopy, atomic force microscopy, drop shape analysis, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, gel permeation chromatography, positron annihilation spectroscopy, and small angle X-ray scattering. All the composite membranes exhibited enhanced radiation resistance properties, with 0.5% loading of NDs as the optimum. Compared to the radiation stability of Psf membranes up to a dose of 100 kGy, the optimum composite membranes are found to be stable up to a radiation dose of 500 kGy, owing to the unique surface chemistry of NDs and interfacial chemistry of Psf-ND composites. Experimental findings along with the Monte Carlo simulation studies confirmed a five times enhanced life-span of the composite membranes in an environment of the intermediate level radioactive waste, compared to the control Psf membrane.

Passive and Active Drug Targeting: Role of Nanocarriers in Rational Design of Anticancer Formulations.

BACKGROUND: Cancer is the major public health problem in developing countries. The treatment of cancer requires a multimodal approach and chemotherapy is one of them. Chemotherapeutic drug is administered to cancer patients in the form of a formulation which is prepared by mixing an active ingredient (drug) with the excipient. The role of excipient in a formulation is to regulate the release, bio-distribution, and selectivity of drug within the body. METHODS: In this context, selectivity of an anticancer formulation is achieved through two mechanisms like passive and active targeting. The passive targeting of a formulation is generally through enhanced permeation retention (EPR) effect which is dictated by physical properties of the carrier such as shape and size. On the contrary, active targeting means surface functionalization of excipient with target-specific ligands and/or receptors to increase its selectivity. RESULTS: Over the past several decades, remarkable progress has been made in the development and application of an engineered excipient or carrier to treat cancer more effectively. Especially nanoparticulate systems composed of metal/liposomes/polymeric material/proteins have received significant attention in the rational design of anticancer drug formulations; for example, therapeutic agents have been integrated with nanoparticles of optimal sizes, shapes and surface properties to improve their solubility, circulation half-life, and bio-distribution. In this review article, recent literature is included to discuss the role of physicochemical properties of excipients in achieving tumour targeting through passive and active approaches. CONCLUSION: The selection of an excipient/carrier and targeting ligand plays a very important role in rational design and development of anticancer drug formulations.

Toxicity and Antigenotoxic Effect of Hispolon Derivatives: Role of Structure in Modulating Cellular Redox State and Thioredoxin Reductase.

Hispolon (HS), a bioactive polyphenol, and its derivatives such as hispolon monomethyl ether (HME), hispolon pyrazole (HP), and hispolon monomethyl ether pyrazole (HMEP) were evaluated for comparative toxicity and antigenotoxic effects. The stability of HS derivatives in biological matrices followed the order HS < HP ≈ HME < HMEP. The cytotoxicity analysis of HS derivatives indicated that HP and HMEP were less toxic than HS and HME, respectively, in both normal and tumor cell types. The mechanisms of toxicity of HS and HME involved inhibition of thioredoxin reductase (TrxR) and/or induction of reductive stress. From the enzyme kinetic and docking studies, it was established that HS and HME interacted with the NADPH-binding domain of TrxR through electrostatic and hydrophobic bonds, resulting in inhibition of the catalytic activity. Subsequently, treatment with HS, HP, and HMEP at a nontoxic concentration of 10 µM in Chinese Hamster Ovary (CHO) cells showed significant protection against radiation (4 Gy)-induced DNA damage as assessed by micronuclei and γ-H2AX assays. In conclusion, the above results suggested the importance of phenolic and diketo groups in controlling the stability and toxicity of HS derivatives. The pyrazole derivatives, HP and HMEP, may gain significance in the development of functional foods.

Diketo modification of curcumin affects its interaction with human serum albumin.

Curcumin isoxazole (CI) and Curcumin pyrazole (CP), the diketo modified derivatives of Curcumin (CU) are metabolically more stable and are being explored for pharmacological properties. One of the requirements in such activities is their interaction with circulatory proteins like human serum albumin (HSA). To understand this, the interactions of CI and CP with HSA have been investigated employing absorption and fluorescence spectroscopy and the results are compared with that of CU. The respective binding constants of CP, CI and CU with HSA were estimated to be 9.3×105, 8.4×105 and 2.5×105M-1, which decreased with increasing salt concentration in the medium. The extent of decrease in the binding constant was the highest in CP followed by CI and CU. This revealed that along with hydrophobic interaction other binding modes like electrostatic interactions operate between CP/CI/CU with HSA. Fluorescence quenching studies of HSA with these compounds suggested that both static and dynamic quenching mechanisms operate, where the contribution of static quenching is higher for CP and CI than that for CU. From fluorescence resonance energy transfer studies, the binding site of CU, CI and CP was found to be in domain IIA of HSA. CU was found to bind in closer proximity with Trp214 as compared to CI and CP and the same was responsible for efficient energy transfer and the same was also established by fluorescence anisotropy measurements. Furthermore docking simulation complemented the experimental observation, where both electrostatic as well as hydrophobic interactions were indicated between HSA and CP, CI and CU. This study is useful in designing more stable CU derivatives having suitable binding properties with proteins like HSA.

Free radical reactions of isoxazole and pyrazole derivatives of hispolon: kinetics correlated with molecular descriptors.

Hispolon (HS), a natural polyphenol found in medicinal mushrooms, and its isoxazole (HI) and pyrazole (HP) derivatives have been examined for free radical reactions and in vitro antioxidant activity. Reaction of these compounds with one-electron oxidant, azide radicals ([Formula: see text]) and trichloromethyl peroxyl radicals ([Formula: see text]), model peroxyl radicals, studied by nanosecond pulse radiolysis technique, indicated formation of phenoxyl radicals absorbing at 420 nm with half life of few hundred microseconds (µs). The formation of phenoxyl radicals confirmed that the phenolic OH is the active centre for free radical reactions. Rate constant for the reaction of these radicals with these compounds were in the order kHI ≅ kHP > kHS. Further the compounds were examined for their ability to inhibit lipid peroxidation in model membranes and also for the scavenging of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical and superoxide ([Formula: see text]) radicals. The results suggested that HP and HI are less efficient than HS towards these radical reactions. Quantum chemical calculations were performed on these compounds to understand the mechanism of reaction with different radicals. Lower values of adiabatic ionization potential (AIP) and elevated highest occupied molecular orbital (HOMO) for HI and HP compared with HS controlled their activity towards [Formula: see text] and [Formula: see text] radicals, whereas the contribution of overall anion concentration was responsible for higher activity of HS for DPPH, [Formula: see text], and lipid peroxyl radical. The results confirm the role of different structural moieties on the antioxidant activity of hispolon derivatives.

Contrasting reactions of hydrated electron and formate radical with 2-thio analogues of cytosine and uracil.

2-Thiocytosine (TC) and 2-thiouracil (TU) were subjected to hydrated electron (eaq-), formate radical (CO2˙-) and 2-hydroxypropan-2-yl radical ((CH3)2˙COH) reactions in aqueous medium. Transients were characterized by absorption spectroscopy and the experimental findings were rationalized by DFT calculations at LC-ωPBE and M06-2X levels using a 6-311+G(d,p) basis set and SMD solvation. In eaq- reactions, a ring N-atom protonated radical of TC and an exocyclic O-atom protonated radical of TU were observed via addition of eaq- and subsequent protonation by solvent molecules. However, two competing but simultaneous mechanisms are operative in CO2˙- reactions with TC and TU. The first one corresponds to formations of N(O)-atom protonated radicals (similar to eaq- reactions); the second mechanism led to 2 center-3 electron, sulfur-sulfur bonded neutral dimer radicals, TCdim˙ and TUdim˙. DFT calculations demonstrated that H-abstraction by CO2˙- from TC(TU) results in S-centered radical which upon combination with TC(TU) provide the dimer radical. In some cases, DFT energy profiles were further validated by CBS-QB3//M06-2X calculations. This is the first time report for a contradictory behavior in the mechanisms of eaq- and CO2˙- reactions with any pyrimidines or their thio analogues.