Nabarun Polley

Modulation of stability and functionality of a phyto-antioxidant by weakly interacting metal ions: curcumin in aqueous solution

The natural polyphenol curcumin and its metal coordinated complexes show obvious benefits in the medical therapies of cancer and several neurodegenerative diseases. On the other side their stability and bioavailability are critical issues. The present study is an attempt to address the stability and functionality of curcumin upon complexation with transition metal ions. We have synthesized and optically characterized metallo–curcumin complexes with Cu(II) and Zn(II). From femtosecond resolved upconversion studies an interaction at the molecular level is revealed based on an observed photoinduced electron transfer from curcumin to the metal ions. In order to investigate the antioxidant activity of the complexes, we have performed a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay in dark. The Cu(II)–curcumin complex exhibits an enhanced and recyclable activity, more pronounced compared to that of the Zn(II)–curcumin complex, which can be attributed to the weaker O–H bond present in the former case. In contrast, the Zn(II) complex has a higher solubility and stability in aqueous media than the Cu(II) complex. To address stability vs. functionality issues, we have suggested a facile method that enhances the solubility and stability of curcumin in aqueous media by metalation with Zn(II) and a successional replacement of Zn(II) in the complex by Cu(II) through a simple route to enhance the activity prior to its use. We have also used the complex in a model anti-bacteriological assay experiment where it shows significantly higher activity compared to pure curcumin. The dichlorofluorescin (DCFH) oxidation indicates an enhancement in ROS generation, which in turn is responsible for the enhanced antioxidative property of the Cu(II)–curcumin complex. Our results provide a promising method to use metallo–curcumin complexes in diverse biological applications.

Unprecedented catalytic activity of Mn3O4 nanoparticles: potential lead of a sustainable therapeutic agent for hyperbilirubinemia

We report an unprecedented catalytic decomposition of aqueous bilirubin solution, without any photo-activation, by citrate functionalized Mn3O4 nanoparticles (NPs). In vitro reactivity of the catalyst on the whole blood specimen of hyperbilirubinemia patients revealed that the catalyst can significantly suppress the total bilirubin level in the blood specimens.

Vitamin B2 in Nanoscopic Environments under Visible Light: Photosensitized Antioxidant or Phototoxic Drug?

Vitamin B2 has been studied as a conventional antioxidant (in the dark) since its discovery in 1926. The effect of visible light on vitamin B2-containing food has a long history of scientific investigation. Although photodegradation of the vitamin producing several photoproducts is evident in certain experimental conditions, phototoxicity revealing an additional oxidative stress in the medium is also clear from some reports. Here we report the photosensitized antioxidant effect of the vitamin, which is found to be greater than 2 orders of magnitude more efficient than that in the dark condition. The photoinduced antioxidant property is apparently paradoxical compared to the reported phototoxic effect of the vitamin. Our present study unravels a unified picture underlying the difference in character of vitamin B2 under visible light irradiation. UV-vis absorption and fluorescence studies in a number of physiologically relevant nanoscopic environments (micelles and reverse micelles) reveal the antioxidant activity to a well-known oxidative stress marker 2,2-diphenyl-1-picrylhydrazyl (DPPH) as well as a phototoxicity effect resulting in self-degradation of the vitamin. Picosecond-resolved Förster resonance energy transfer (FRET) from the vitamin to the marker DPPH in the biomimetic environments clearly reveals the role of proximity of an oxidizing agent in the photoinduced effect of the vitamin. Our systematic and detailed studies unravel a simple picture of the mechanistic pathway of the photosensitized vitamin in the physiologically important environments leading to the antioxidant/phototoxicity effect of the vitamin. The excited vitamin transfers its electron to the oxidizing agent in proximity for the antioxidant effect, but otherwise it employs oxygen to generate reactive oxygen species (ROS), resulting in phototoxicity/self-degradation.

Safe and symptomatic medicinal use of surface-functionalized Mn3O4 nanoparticles for hyperbilirubinemia treatment in mice

AIM Testing the potential of citrate-capped Mn3O4 nanoparticles (NPs) as a therapeutic agent for alternative rapid treatment of hyperbilirubinemia through direct removal of bilirubin (BR) from blood in mice. MATERIALS & METHODS NPs were synthesized and the mechanism of BR degradation in presence and absence of biological macromolecules were characterized in vitro. To test the in vivo BR degradation ability of NPs, CCl4-intoxicated mice were intraperitoneally injected with NPs. RESULTS We demonstrated ultrahigh efficacy of the NPs in symptomatic treatment of hyperbilirubinemia for rapid reduction of BR in mice compared with conventional medicine silymarin without any toxicological implications. CONCLUSION These findings may pave the way for practical clinical use of the NPs as safe medication of hyperbilirubinemia in human subjects.

Allosteric Inhibitory Molecular Recognition of a Photochromic Dye by a Digestive Enzyme: Dihydroindolizine makes α-chymotrypsin Photo-responsive.

The structural-functional regulation of enzymes by the administration of an external stimulus such as light could create photo-switches that exhibit unique biotechnological applications. However, molecular recognition of small ligands is a central phenomenon involved in all biological processes. We demonstrate herein that the molecular recognition of a photochromic ligand, dihydroindolizine (DHI), by serine protease α-chymotrypsin (CHT) leads to the photo-control of enzymatic activity. We synthesized and optically characterized the photochromic DHI. Light-induced reversible pyrroline ring opening and a consequent thermal back reaction via 1,5-electrocyclization are responsible for the photochromic behavior. Furthermore, DHI inhibits the enzymatic activity of CHT in a photo-controlled manner. Simultaneous binding of the well-known inhibitors 4-nitrophenyl anthranilate (NPA) or proflavin (PF) in the presence of DHI displays spectral overlap between the emission of CHT-NPA or CHT-PF with the respective absorption of cis or trans DHI. The results suggest an opportunity to explore the binding site of DHI using Förster resonance energy transfer (FRET). Moreover, to more specifically evaluate the DHI binding interactions, we employed molecular docking calculations, which suggested binding near the hydrophobic site of Cys-1-Cys-122 residues. Variations in the electrostatic interactions of the two conformers of DHI adopt unfavorable conformations, leading to the allosteric inhibition of enzymatic activity.

Development and optimization of a noncontact optical device for online monitoring of jaundice in human subjects

Abstract. Jaundice is one of the notable markers of liver malfunction in our body, revealing a significant rise in the concentration of an endogenous yellow pigment bilirubin. We have described a method for measuring the optical spectrum of our conjunctiva and derived pigment concentration by using diffused reflection measurement. The method uses no prior model and is expected to work across the races (skin color) encompassing a wide range of age groups. An optical fiber-based setup capable of measuring the conjunctival absorption spectrum from 400 to 800 nm is used to monitor the level of bilirubin and is calibrated with the value measured from blood serum of the same human subject. We have also developed software in the LabVIEW platform for use in online monitoring of bilirubin levels in human subjects by nonexperts. The results demonstrate that relative absorption at 460 and 600 nm has a distinct correlation with that of the bilirubin concentration measured from blood serum. Statistical analysis revealed that our proposed method is in agreement with the conventional biochemical method. The innovative noncontact, low-cost technique is expected to have importance in monitoring jaundice in developing/underdeveloped countries, where the inexpensive diagnosis of jaundice with minimally trained manpower is obligatory.

Development and validation of a noncontact spectroscopic device for hemoglobin estimation at point-of-care

Abstract. Anemia severely and adversely affects human health and socioeconomic development. Measuring hemoglobin with the minimal involvement of human and financial resources has always been challenging. We describe a translational spectroscopic technique for noncontact hemoglobin measurement at low-resource point-of-care settings in human subjects, independent of their skin color, age, and sex, by measuring the optical spectrum of the blood flowing in the vascular bed of the bulbar conjunctiva. We developed software on the LabVIEW platform for automatic data acquisition and interpretation by nonexperts. The device is calibrated by comparing the differential absorbance of light of wavelength 576 and 600 nm with the clinical hemoglobin level of the subject. Our proposed method is consistent with the results obtained using the current gold standard, the automated hematology analyzer. The proposed noncontact optical device for hemoglobin estimation is highly efficient, inexpensive, feasible, and extremely useful in low-resource point-of-care settings. The device output correlates with the different degrees of anemia with absolute and trending accuracy similar to those of widely used invasive methods. Moreover, the device can instantaneously transmit the generated report to a medical expert through e-mail, text messaging, or mobile apps.

Evanescent field: A potential light-tool for theranostics application

A noninvasive or minimally invasive optical approach for theranostics, which would reinforce diagnosis, treatment, and preferably guidance simultaneously, is considered to be major challenge in biomedical instrument design. In the present work, we have developed an evanescent field-based fiber optic strategy for the potential theranostics application in hyperbilirubinemia, an increased concentration of bilirubin in the blood and is a potential cause of permanent brain damage or even death in newborn babies. Potential problem of bilirubin deposition on the hydroxylated fiber surface at physiological pH (7.4), that masks the sensing efficacy and extraction of information of the pigment level, has also been addressed. Removal of bilirubin in a blood-phantom (hemoglobin and human serum albumin) solution from an enhanced level of 77 μM/l (human jaundice >50 μM/l) to ~30 μM/l (normal level ~25 μM/l in human) using our strategy has been successfully demonstrated. In a model experiment using chromatography paper as a mimic of biological membrane, we have shown efficient degradation of the bilirubin under continuous monitoring for guidance of immediate/future course of action.

Citrate functionalized Mn3O4 in nanotherapy of hepatic fibrosis by oral administration

Aim: To test the potential of orally administered citrate functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs) as a therapeutic agent against hepatic fibrosis and associated chronic liver diseases. Materials & methods: C-Mn3O4 NPs were synthesized and the pH dependent antioxidant mechanism was characterized by in vitro studies. CCl4 intoxicated mice were orally treated with C-Mn3O4 NPs to test its in vivo antioxidant and antifibrotic ability. Results: We demonstrated ultrahigh efficacy of the C-Mn3O4 NPs in treatment of chronic liver diseases such as hepatic fibrosis and cirrhosis in mice compared with conventional medicine silymarin without any toxicological implications. Conclusion: These findings may pave the way for practical clinical use of the NPs as safe medication of chronic liver diseases associated with fibrosis and cirrhosis in human subjects.

Medical diagnosis and remote sensing at fiber-tip: picosecond resolved FRET sensor

Förster Resonance Energy Transfer (FRET) strategy in popular in fiber-optic sensing. However, the steady state emission quenching of the donor is inadequate to conclude FRET. The resonance type energy transfer from one molecule (donor) to other (acceptor) should meet few key properties including donor to acceptor energy migration in non-radiative way. In the present study, we have coupled the evanescent field of an optical fiber to the covalently attached donor (dansyl) molecules at the fiber tip. By using picosecond resolved time correlated single photon counting (TCSPC) we have demonstrated that dansyl at the fiber tip transfers energy to a well known DNA-intercalating dye ethidium. Our ultrafast detection scheme selectively distinguishes the probe (dansyl) emission from the intrinsic emission of the fiber. We have also used the setup for the remote sensing of the dielectric constant (polarity) of an environment. We have finally implemented the detection mechanism to detect an industrial synthetic dye methylene blue (MB) in water.