Dr. Mithun Roy
Welcome to the Group of Synthetic Inorganic Chemistry, Medicinal Inorganic Chemistry and Bioinorganic Chemistry
Dr. Mithun Roy @ NIT Manipur
National Institute of Technology, Manipur
Research Interest
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Modular approach to DNA-based catalyst: Sustainable Approach.
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Exploring Photochemistry of Transition metal complexes for photo-activated chemotherapy (PACT).
Present research at NIT Manipur
Modular approach to DNA-based catalyst: Sustainable Approach
The principal scientific goal of this project is to implement a new modular approach for the synthesis of asymmetric catalysts which employ DNA as a scaffold to impart chiral information. In the proposed project the redox nature of the bpDNA was used to conjugate achiral catalyst. The methodology would result in a simple method to anchor suitable catalyst to the nucleic acid support which, crucially, may be applied to a wide range of transition metal and organo-catalysts.
This project is funded by DST-SERB (ECR-2016-000839).
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Exploring photochemistry of transition metal complexes for photo-activated chemotherapy
Cancer is among the leading causes of mortality worldwide with 8.2 million related deaths and 14 million new cases in 2012 and the projected cancer-related death is estimated to be 13.1 million in 2030. Therefore efforts are needed to find more targeted, cost-effective cancer therapeutic modalities. Among the present cancer treatment modalities high recurrence rate associated with surgical resection of tumors, high radiation dose in radiotherapy and systemic side-effects in chemotherapy have limited such treatment modalities in anti-cancer research. Photodynamic therapy (PDT) has emerged as an alternative non-invasive, tumor-ablative treatment modality in which a tumor-localizing photo-sensitizer (PS) for example photofrin® is administered followed by localize illumination of the tumor with the red-light. In this process singlet oxygen (1O2) is oxidizing key cellular macromolecules leading to tumor cell ablation. Hence, PDT ensure significantly higher tumor specificity as the photoexposure to the PS is highly localized only in tumors unlike chemotherapy and radiation therapy. However, PDT has yet to gain clinical acceptance as a first-line oncological intervention due to the lack of an ideal PS free from any systemic side effects. Photo-activated states of transition metal complexes displaying several chemical reactions can be best explored for photo-chemotherapeutic applications. Our present research explore photo-redox chemistry, photo-chemical ligand exchange reactions of the visible-light (PDT window) activated transition metal complexes for photo-activated chemotherapeutic applications.
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Ref: (1) S. Binita Chanu, Samya Banerjee, Mithun Roy* "Potent anticancer activity of photo-activated oxo-bridged diiron(III) complexes" Eur. J. Med. Chem., 2016, In press, http://dx.doi.org/10.1016/j.ejmech.2016.09.090.
(2) S. Binita Chanu, Samya Banerjee, Arun Kumar, Mithun Roy* "ROS dependant antitumor activity of photo-activated iron(III) complexes of amino acids" Manuscript under preparation.
(3) Dulal Musib, Samya Banerjee, Aditya Garai, Mithun Roy* "Photo-activated anticancer activity of L-histidinito copper(II) complexes: From theory to biological evaluation. Manuscript under preparation.
Past research
Improved synthesis of longer DNA (>100 bp).
The work was carried out at University of Colorado, Boulder with Prof. Marvin H Caruthers in collaboration with Agilent Technologies
Synthetic oligonucleotides have become the daily tool to explore molecular biology, medicinal chemistry and material chemistry. The chemical synthesis of nucleic acids has been performed using variations of the phosphoramidite chemistry on solid surfaces. This chemistry in solid surface has now become a very important and daily tool to explore the synthesis to the chemistry of nucleic acid. The only reasons for this universal acceptance are both the efficiency of the chemistry and its versatility resulting in numerous adaptations to achieve specific needs. For instance, phosphoramidite based methods have been used to synthesize abundant base, backbone and sugar modifications of deoxyribo and ribonucleic acids, as well as nucleic acid analogs. While the phosphoramidite chemistry has been used to synthesize these analogs individually on a medium-to-large scale, high throughput biological studies that involve thousands of genes demanded new parallel DNA synthesis methods. For this purpose, the phosphoramidite chemistry has been adapted for in situ synthesis of DNA microarrays and synthesis of high-quality libraries of long oligonucleotides (150mer) by a novel depurination controlled process was successful in DNA microarray synthesis. However, with the increase in DNA length the yield is decreased significantly because of several side reactions during the solid-phase synthesis. The side reactions are the failure sequences, various adduct formations during the synthesis, depurination or post synthesis procedure. Therefore it is a demand to explore new method or new type of phosphoramidite synthons to have much more cleaner synthesis of longer DNA with no side reaction. Significantly cleaner syjthesis was acheived by modification at base or by using different amine protecting groups. The research was based on to explore new phosphoramidite synthons other than the commercially available synthons to minimize the side reaction related to the adduct formations during synthesis or post-synthetic procedure in the solid-phase synthesis of longer DNA.
Patent:
Title: Phosphorus protecting groups and methods of preparation and thereof.
Inventors: Douglas J. Dellinger, Luca Monfregola, Marvin H. Caruthers, Mithun Roy,
International Publication Number: WO 2015/168461 A2, Date: November 05, 2015.
Pyridinylboranephosphonate DNAs-New Analogues for Biological and Nanotechnological Applications
The work was carried out at University of Colorado, Boulder with Prof. Marvin H Caruthers
Synthetic, chemically modified oligodeoxynucleotides are important for a large number of applications in biology, diagnostics and materials research. Because this field continues to grow rapidly, there is an increasing need to develop analogues with new chemical, biological and biophysical properties. Here we describe the synthesis of a previously unknown class of analogues having pyridinylboranephosphonate internucleotide linkages. These linkages are best characterized by replacing one of the nonlinking, internucleotide oxygens with a pyridinylborane functional group. The chemistry is carried out by iodine oxidation of a boranephosphonate internucleotide linkage in the presence of pyridine or a substituted pyridine. The chemistry was also found to be orthogonal with other unsaturated amines such as N-methylimidazole or 4-methylquinoline. By substituting various pyridine derivatives, ODNs have been synthesized that are rapidly transfected into HeLa cells in the absence of lipid or have conjugated Cu2+ and Mn2+ complexes with pendant pyridinyl groups. We have also studied modulating the redox behavior of the boranephosphonate and pyridinylboranephosphonate conjugated linkages. Boranephosphonate reduces Au3+ and Pt2+ to nanoparticles, whereas the pyridinyl conjugate reduces Au3+ to Au-nanoparticles (AuNPs) very slowly when compared to boranephosphonate and cannot reduce Pt2+. These observations should prove useful for future selective nanofabrication of DNA arrays.
Ref:Subhadeep Roy, Sibasish Paul, Mithun Roy, Luca Monfregola, Marvin H Caruthers, "Pyridinium Boranephosphonate Modified DNA Oligonucleotides" Submitted to J. Org. Chem. 2016
Doctoral Work
Aspects of the chemistry of iron complexes in showing DNA photocleavage activity
The work was carries out at Indian Institute of Science, Bangalore under the supervision of Prof. Akhil R. Chakravarty
My thesis work focused mainly on the design and synthesis of photoactive iron complexes that efficiently bind and cleave DNA on visible light irradiation under the physiological condition in absence of any external agents for their potential utility in photoactivated chemotherapy. The primary research work is based on the multistep organic synthesis and the synthesis of metal-organic hybrids (transition metal complexes), studies on DNA binding and photocleavage activities and to explore the mechanism of DNA cleavage. Synthetic proteases that can cleave protein backbone with a high specificity are useful as multifunctional biochemical agents suitable for medicinal applications and for understanding the structure–activity correlations of proteins and towards exploring different structural domains in proteins. My research work also deals with the studies on protein binding and cleavage by the iron complexes. Significantly important result in achieving site specific protein cleavage on photoactivation of iron complex was obtained during my studies. Title of dissertation is “Aspects of the chemistry of iron complexes in showing DNA photocleavage activity”.
Impact of the thesis work: The results are of importance in designing new iron(III)-based synthetic photonucleases with potential utility in nucleic acid chemistry and phototherapy.