IOSR Journal of Applied Chemistry (IOSR-JAC) e-ISSN: 2278-5736.Volume 11, Issue 2 Ver. I (February. 2018), PP 40-54 www.iosrjournals.org DOI: 10.9790/5736-1102014054 www.iosrjournals.org 40 |Page An Insight Into The Interaction of Risedronate Sodium With Human Serum Albumin By Absorption, FT-IR, Fluorescence, SEM, Voltammetry And Molecular Docking Studies Manjushree M, Hosakere D Revanasiddappa* Department of Chemistry, University of Mysore, Manasagangothri, Mysuru 570 006, Karnataka, India *Corresponding Author: Hosakere D. Revanasiddappa (hdrevanasiddappa@yahoo.com) Abstract: Interaction between human serum albumin (HSA) and risedronate sodium (RDT) was investigated by employing (emission and synchronous) fluorescence, ultraviolet–visible (UV-Vis) absorption, Fourier transform infrared (FT-IR) spectroscopic methods, voltammetry, scanning electron microscope (SEM) and molecular docking studies at physiological buffer conditions (pH 7.4). Stern–Volmer and Modified Stern–Volmer equations showed that static quenching, Van’t Hoff equation determined the interaction is spontaneous process and the binding is through hydrogen bonds and vander Waals forces. FT-IR reveals that the secondary structure of HSA was altered upon interaction with RDT. UV-Vis, SEM and voltammetric studies were given the information on complex formed between HSA and RDT. The conformation and microenvironment of HSA were changed after the interaction of RDT this was studied by synchronous fluorescence. The calculated binding constant is of the order of 10 5 suggesting that very sTABLE binding. The effects of Fe 2+ , Cu 2+ and Zn 2+ ions were also studied on the binding interaction between HSA and RDT that yields low binding constant values. The binding sites for RDT are present in site III (sub-domain IB) were achieved by ligand displacement and molecular docking studies. This study gives us information on transportation, distribution and toxicity effect of RDT when it enters into human blood serum and it has wide applications in pharmaceutical industry, life sciences and clinical medicine. Keywords: Human serum albumin; Risedronate sodium; Metal ions; Fluorescence spectroscopy; Molecular docking; Binding mechanism --------------------------------------------------------------------------------------------------------------------------------------- Date of Submission: 25-01-2018 Date of acceptance: 12-02-2018 --------------------------------------------------------------------------------------------------------------------------------------- I. Introduction Risedronate sodium, chemically known as [1-hydroxy-2-(3-pyridinyl)ethylidene]bisphosphonic acid] monosodium salt (Fig.1), which is employed mainly for the treatment of integral skeletal disorders like osteoporosis, Paget‟s disease of bone (osteitis deformans) and also used to strengthen bone. Risedronate sodium is used to suppress osteoclast-mediated bone, inflects bone metabolism and also preventing osteoporosis in postmenopausal women [1-3]. Drug has the important property to bind protein that effects the drug solubility, bioavailability and its half-life in the body. The important protein present in blood plasma is serum albumin involved in drug delivery process into affected tissues in the body. If, binding interaction between serum albumin and drugs is stronger, the availability of free drug is lower; on the other hand, weaker the binding interaction between serum albumin and drugs can lead to a poor distribution of drugs in vivo. Therefore, the research on binding interaction between serum albumin with drugs is needful for understanding the action mechanism and pharmacology of drugs [4-7]. High concentration of HSA is present in blood plasma (40 mg/ml or 0.6 mM). This is a globular protein, containing 585 amino acid residues, and it is composed of three structurally similar domains (I, II and III) assemble to form a heart-shaped molecule, each consisting of two sub-domains (A and B) and stabilized by 17 disulfide bridges. Aromatic and heterocyclic ligands usually bind to two hydrophobic pockets in sub-domains IIA and IIIA, called as site I and site II. Seven binding sites are located for fatty acids are sub-domains IB, IIIA, IIIB and on the sub-domain interfaces [8]. They have also high affinity metal binding sites at the N-terminus. HSA has one tryptophan residue Trp-214 that possesses intrinsic fluorescence. Many metal ions in blood plasma play very important role in biochemical processes. HSA usually acts as a sequestration agent of metal ions and has a variety of metal binding sites with different specificities. The trace elements in biological system may alter the efficacy of the drug; these metal ions are administered along with drug as mineral supplements. The activity of antibiotics, antibacterials, antiviral agents and other drug molecules are affected or sometimes influenced by the interaction of metal ions [9, 10].