Department of Chemistry
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Item Open Access Photophysical and sensorial behaviour of different chromophoric systems comprising electron donor-acceptor units(University of North Bengal, 2023) Rahman, Ziaur; Das, Sudhir KumarResearch on developing new electron donor–acceptor (EDA) based molecular systems, which benefit from extended π-conjugation, is a rapidly growing research area. That has resulted in several technological applications, including fluorescent dyes, laser dyes, brightening agents, metal sensors, pH sensors, bio-imaging, organic photovoltaics (OPVs), organic light-emitting diodes (OLEDs), and many more. The photophysical properties of donor (D)-acceptor (A) based molecular systems depend on the substitution pattern and the D-A unit's nature, making them prime derivatives for application in organic photonics. The most frequent method for tuning the photophysical properties of organic compounds is to connect an electron-rich “D” and an electron-deficient “A” group directly or indirectly. The π-linkage between the “D” and “A” units results in a D-π-A type of conjugated molecular system, where the photophysical/electronic properties of D-π-A systems can be tuned by either (i) changing the “D” or “A” unit strength or (ii) varying the π-linker between the “D” and “A” units. A wide range of D-A conjugated systems with varying “D” and “A” units have been developed for various applications in chemistry, physics, materials science, and biology. Because of their superior photophysical characteristics, these are used to develop and create various sensory materials for monitoring biological events and detecting various target analytes. Chemosensors based on photoluminescence are essential among the many approaches and methodologies because they have multiple benefits, such as on-site detection, real-time monitoring with rapid response, innately high sensitivity, and simplicity of handling compared to other techniques. Considering the real benefit of the chromo-fluorogenic EDA system, present thesis explores its practical benefit for detection of various target analytes. A brief summary of each chapter of the present thesis are given below one by one. Chapter 1: This chapter begins with a brief discussion of the EDA system-based chemosensors and then moves to the general principle and working mechanism for designing chemosensors based on different photophysical processes with examples. This chapter deals with the objectives and applications of the present work in the present context of scientific development. Chapter 2: This chapter explores the reversible acidochromic behavior of a benzoxazole-based scaffold (BPP), which is highly sensitive to the acid-base in the liquid and gas phases. With the addition of acid, the solution of BPP changes its color from yellow to pink fuchsia due to the transformation of its imine into quinonoid form. The color change is completely reversible in the presence of the base, confirming the reversible acidochromic behavior of the present BPP system. Further, a paper strips-based test kit has been demonstrated for the practical utility of the present acidochromic BPP to identify a trace amount of acid-base in solution and gas-phase, respectively. The mechanistic aspects of detecting acid-base and colorimetric change in the presence of acid-base have been explored by density functional theoretical investigations and 1H NMR experiments. Moreover, we have constructed a reconfigurable dual-output combinatorial INH/IMP logic gate. Chapter 3: This chapter highlights the investigation of anion interactions and recognition abilities of naphthalene derivative, [(E)-1-(((4-nitrophenyl) imino) methyl) naphthalen-2-ol], (NIMO) by UV–visible spectroscopically and colorimetrically. NIMO shows selective recognition of F− ions colorimetrically, and the naked eye observes a visual color change from yellow to pink. The F− ions recognition is fully reversible in the presence of HSO4− ions. The limit of F− ions detection by NIMO could be possible down to 0.033 ppm-level. A paper strips-based test kit has been demonstrated to detect F− ions selectively by the naked eye, and a smartphone-based method for accurate sample analysis in the non-aqueous medium has also been demonstrated. The pKa value calculation and DFT analysis support spectroscopic behavior to find a correlation with receptor analyte interaction. The optical response of NIMO towards the accumulation of F− ions and, subsequently, HSO4− ions as chemical inputs provide an opportunity to construct INH and IMP molecular logic gates. Chapter 4: In this chapter, a fluorosensor derived from 4-aminophthalimide, ((E)-5-((2-hydroxy benzylidene) amino) isoindoline-1, 3-dione, HID working with excited state intramolecular proton transfer (ESIPT) mechanism is synthesized and employed for the selective recognition of aluminum (Al3+) ions and picric acid (PA) based on 'off-on-off' fluorescence mechanism. The sensor HID shows a turn-on fluorescence response towards Al3+ ions in H2O/DMSO (9:1, V/V) with a rapid response time (2 minutes) and exceptional sensitivity (LOD = 0.77 μM). The binding constant (K) of HID with Al3+ ions is estimated to be 1.32 × 108 M-2. The 1:2 stoichiometries of the complex between HID and Al3+ ions are confirmed through Job's plot and 1H NMR spectral analysis. Al3+ chelated HID complex is further employed to detect explosive nitroaromatic compounds, especially PA. Furthermore, using these two chemically encoded inputs, and corresponding optical output, we constructed the INH molecular logic gate with Al3+ and PA. The HID chemosensor and Al3+ chelated HID complex are also applied to map Al3+ ions and PA in the living cell. The HID chemosensor and Al3+ chelated HID complex's performance toward detecting Al3+ ions, and PA demonstrates that it might be used as a signaling tool for analyzing biological and environmental samples. Chapter 5: This chapter attempts to introduced a photoluminescence ionic liquid and its application for detecting nitro explosives. Due to the rising menace of illicit actions and pollution aroused by explosive nitroaromatic compounds (NACs), the growth of an adept sensor for detecting these NACs is essential. Herein, in this communication, a photoluminescent IL-assimilated group of uniform materials based on organic salt (GUMBOS) and Nano-GUMBOS has been fabricated by integrating pyrene butyrate with a quaternary phosphonium IL (PbIL) via a simple ion exchange process. Neat PbIL shows a bright cyan color photoluminescence under a 365 nm UV lamp irradiation and is employed as photoluminescence security ink and picric acid (PA) detection among the tested NACs. By simple reprecipitation method, we have developed water-suspended crystalline pyrene assimilated nanoparticles, nPbIL, characterized by various analytical techniques. The PbIL-derived water-suspended nanomaterials, nPbIL, display a robust cyan color excimer-like emission, which turns blue (monomeric) due to adding PA over the other related NACs. This ratiometric cyan-to-blue photoluminescence change is due to the displacement of the anionic pyrene moiety of the nPbIL by the picrate anion. The fabricated organo nanosensor is enormously discerning and responsive towards PA with a LOD of 0.77 nM and is superior to many available in the literature. Additionally, a fluorogenic paper strip-based test kit experiment has been demonstrated to detect and quantify PA selectively in aqueous solvents amongst the other tested NACs. The present contribution evokes a novel approach to developing different IL-based chemosensors for detecting and quantifying various target analytes. Chapter 6: This chapter attempts to demonstrate the role of different mimics of G-series nerve agents and their detection method. There is a pressing need for rapid and accurate recognition of hazardous G-series nerve agents in the solution and vapor phases to protect individuals from undesirable wars and terrorist attacks. However, achieving this goal in practice presents significant challenges. This contribution introduces a specific and selective acridine-based fluorogenic sensor, AMA, which exhibits turn-on behavior from cyan to blue photoluminescence under the exposure of a 365 nm UV lamp in response to diethylchlorophosphate (DCP), a mimic of sarin gas, in both liquid and vapor phases, respectively. The mechanism underlying the identification of DCP using AMA has been elucidated through 1H-NMR titration investigation and HRMS analaysis. The fluorgenic, DCP-specific AMA shows an outstanding selectivity, excellent sensitivity, and a broad linear span of 15-38 μM, with an identification limit of 7.9 nM, which is found to be superb than many chemosensors available in the literature without any interference. To facilitate its potential practical applications, we have introduced an AMA-coated test kit utilizing Whatman-41 filter paper, which can be used as a handy and visual photonic device for on-spot identification of DCP as a mimic for sarin gas under the colonial crowding condition of other analogous analytes. Furthermore, we have demonstrated a fluorogenic dip-stick method to detect and quantify the DCP vapor under the exposure of a 365 nm UV lamp. Chapter VII: Finally, a brief summary of the present thesis and the future perspective from the present research work has been delineated in this chapter.Item Open Access Metal free C- H Functionalization: a unique tool for library synthesis of functionalized 4- pyrimidiones(University of North Bengal, 2023) Roy, Sanjay; Das, SajalThe Present Thesis entitled as “Metal free C- H Functionalization: a unique tool for library synthesis of functionalized 4-pyrimidiones” has made some efforts to synthesize the diverse 4 pyrimidones with varied functional groups via different approaches and their applications in medicinal and pharmacological domains. Based on different direction and contents of the work; the thesis has been divided into four chapters. Chapter I: describes an introduction to present work, the “A brief review on C-H functionalization/activation and a literature study regarding the synthesis of 4Hpyrido[ 1,2-a]pyrimidin-4-one derivatives” Summarizes a brief review on pyrimidines and it was further subdivided into following points: 1) Origin, background theory, importance and current status of C-H Functionalization. 2) Use of C-H functionalization techniques in selective functionalization of heterocycles. 3) Importance of 4-pyrimidiones and current literature status 4) Different approaches of its synthesis and further derivatization Chapter II: describes “Microwave-assisted straight forward synthesis of 2-substituted alicyclic fused pyrimidone” We have divulged here a metal free- and MW assisted route to tetrahydro-4H-pyrido[1,2- a]pyrimidin-4-one and dihydropyrrolo[1,2-a]pyrimidin-4(6H)-one has been demonstrated by the reaction of aminoacrylates with lactams in presence of phosphorous pentachloride. This transformation comprises of the sequential formation of three new bonds to produce pyrimidone derivatives under mild reaction conditions and this strategy is well compatible for both electron deficient and electron rich amino-acrylates. This method is amenable for gram scale reaction.Item Open Access Assorted interactions of some antibacterial and anticancer drug molecules and ionic liquids prevaling in supramolecular and solution chemistry investigated by experimental and computational apporach(University of North Bengal, 2023) Sharma, Antara; Roy, Mahendra NathProposed work covers the Supramolecular Host-Guest Inclusion Complexation of some bioactive molecules and the solute-solvent interaction of amino acids (AA) with ionic liquids (ILs) aiming to compare the molecular interaction existing among these different chemical compounds and resulting molecular synergism in solution phase. Supramolecular assemblage has garnered a huge importance during recent years in the field of drug delivery owing to their significant biocompatibility and excellent potential to expand the spectrum of medical application in pharmaceutical industries and biomedical sciences. The spectroscopic techniques confirm the inclusion complex formation of numerous bioactive molecules and their photophysical properties in solution phase. The UV-Visible, 1H NMR and FT-IR spectroscopy along with mass spectrometry studies supports the formation of inclusion complex. Further, SEM and PXRD analysis implements the qualitative aspect for the generation of supramolecular framework. Thermal and photostability of such assembly have been examined through DSC and UV- visible studies. Computational and theoretical molecular modelling studies of this system reaffirms the results observed in the experimental studies. In this study, inclusion of variety of biologically potent molecules such as, Rodanine, Gemcitabine and Nitrofurantoin have been examined. These compounds find significant medicinal applications. Pharmacological aspect is specifically considered to illustrate the biocompatibility of such biologically active molecules. Molecular recognition, controlled release of a drug and sensing field have received the great consideration under host–guest chemistry. Encapsulation of guest molecules in aqueous phase inside the nanocage of host molecules, such as cyclodextrins and several other water-soluble hosts lights up an advanced technique into the field of molecular recognition (inclusion or complexation) owing to extensive non-covalent interactions. The potent pharmacological activity of bioactive compounds often gets influenced through molecular recognition. Supramolecular host-guest chemistry covers a broad aspect related to the inclusion complex formation between the host and the guest molecules. Hydrophobic nanocage of host molecules are very efficient in binding variety of guest molecules. Over the past few decades, the supramolecular assembly has been extensively investigated in several fields including analytical chemistry and drug-delivery. Cyclodextrins (CDs), are the most suitable host compounds owing to their ability for controlled passage of guest molecules after inclusion complex formation thereby increasing bioavailability of the compound. Ionic liquids (IL) or famously known as molten salts at room temperature currently received great consideration in many areas of chemistry by the researchers across the globe. The most significant characteristic of ILs is the “tunability” of various physical and chemical properties by modifying structure. Many reviews have highlighted the different characteristics of ILs and their potential application. ILs are blessed with some exceptional properties as most of them have a negligible vapor pressure, unparalleled thermal and electrochemical stability, low flammability and commending dissolution properties with large variety of organic/inorganic compounds. ILs mainly consist of different category of cations and anions. They found significant applications as biphasic systems for separation, solvents for many synthetic and catalytic applications, lubricants, extensively in lithium batteries, supercapacitors, actuators, substitute for conventional solvents, alternative for reaction media and active pharmaceutical ingredients. However, the most important characteristic associated with ILs is the “tunability” of their structure. They can easily modify their structure to achieve the specific chemical or electrochemical applications. In order to investigate the stability of proteins, (ILs) are generally employed as a novel medium . Amino acids are considered ideal system for investigating the characteristics of proteins. Further denaturation, solvation and dissociation of enzyme are highly affected by the neighbouring environment. The emergence of assorted interactions is conventionally examined by estimation of the apparent molar volume ( v ), limiting apparent molar volume ( 0 v ), molar refraction ( M R ), limiting molar refraction ( 0 M R ) viscosity B coefficients obtained from different physicochemical methodologies. This study features the variety of physicochemical characteristics of amino acid in solution of Ionic liquid in water. This work helps in interpretating the behaviour of these compounds in complex structures of proteins. Here we have selected an Ionic liquid as an additive (electrolyte) as they are blessed with various advantages as a function of concentration, temperature, and ambient pressure. Thermodynamic, viscometry, volumetric, refractometric, surface tension measurements have been carried out as these properties are susceptible towards the solute-solute and solute-solvent interaction. Investigation of these properties greatly support to understand the structure and characteristics of solutes in aqueous medium and gives a reliable explanation for the complicated nature of molecular interactions in various biochemical processes occurring in the human body. Therefore, the objective of this thesis is to (1) investigate and understand the significance of supramolecular recognition owing to their diverse range of applications in varied fields such as pharmaceutical, biomedical sciences etc. (2) understand and evaluate the molecular interactions between ionic liquid and various biomolecules in order to manifest the behaviour of these compounds in complex structures of proteins for further application. Summary of work done Chapter I This chapter contains the details of the research work, their objective, scope and applications in the modern science. A detailed discussion about the scope of selecting the biologically active molecules, cyclodextrins, amino acids and ionic liquids have been included. This chapter consist a brief list of all the techniques of investigations i in the research work. Chapter II This chapter consist the review of the previous works reported by scientists and researchers in the field of supramolecular and solution chemistry around the world. This chapter also includes the detail of theories of investigation. The interactive forces existing among the various molecules have been discussed in detail. The underlying theories of investigating techniques, i.e., theory of 1H NMR , FT-IR, Fluorescence, UV-Visible spectroscopy, Mass spectrometry and Thermogravimetric analysis, Powder X-ray Diffraction, Scanning Electron Microscopy, Surface tension study, Molecular docking study, Antibacterial activity study, Cytotoxicity study, CT-DNA interaction study, Photostability study, Surface tension, Conductivity, Density, Viscosity, Refractive index studies have been discussed thoroughly and the importance of this research work also included in this thesis. Chapter III This chapter presents the experimental section. It includes the details of name, structure, physical properties and applications of the biologically active molecules, cyclodextrins, amino acids, ionic liquids and solvents used in the research work. It consists the briefing about the experimental methodologies. Chapter IV This chapter contains of the encapsulation of rhodanine within the cavity of α-cyclodextrin and β- cyclodextrin. This work has been investigated by spectroscopic, physicochemical methods. Job plots using UV-Visible spectroscopy confirms the 1:1 stoichiometry of the host-guest molecular assembly. This observation was again supported by mass spectrometric analysis. UV-Visible spectroscopy has been employed to calculate association constants for the inclusion complexes using Benesi– Hildebrand method. Thermodynamic parameters have been calculated and it ascertains the thermodynamically spontaneity of the overall inclusion processes. 1H NMR and FT-IR investigations illustrates the quantitative insight on the possible mode of encapsulation in inclusion complexes. Thermal stability of rhodanine on inclusion with cyclodextrins has been evaluated by DSC analysis. Computational study further provides the useful understanding on the inclusion mode of rhodanine molecule into the nanocage of cyclodextrins. The surface morphology of the inclusion complexes was investigated by SEM. Photostability and CT-DNA interaction studies are investigated by UV Visible spectroscopy. Finally, the biological activity namely; cytotoxicity and antimicrobial activity of the inclusion complexes were evaluated and a comparative study was carried out with respect to pure rhodanine. Chapter V This chapter presents the study of the host-guest inclusion complex of gemcitabine with β-cyclodextrin, photostability, CT-DNA study and its biological activity. The prepared complex was characterized by numerous physicochemical and spectroscopic methods. Job plot, and mass spectrometric analysis confirms the 1:1 ratio host-guest inclusion complex. Association constant has been determined by Benesi–Hildebrand method. The Gibb’s free energy of binding has been calculated by evaluating the binding constant which confirms the inclusion process is spontaneous. The mode of inclusion was investigated by 1H NMR and FT-IR spectroscopic analysis. PXRD and SEM analysis have been carried to reaffirm the inclusion complex formation. The enhancement in the photo stability of gemcitabine through complexation was investigated by UV-visible spectroscopic analysis. Molecular docking study presented the most preferred site for binding of gemcitabine molecule within the cavity of β-cyclodextrin. The apoptosis and antibacterial activity of the inclusion complex was investigated in detail and subsequently compared with free gemcitabine. Chapter VI This chapter presents the thorough analysis on the diverse molecular interactions of implausible amino acid, L-leucine (AA) in the aqueous solution of Benzyltriethylammoniun chloride (BTEACl), Benzyltributylammoniun chloride (BTBACl) have been carried out by numerous physicochemical techniques such as Density, Refractive index, Viscosity, Electrical conductivity, at four different temperatures ranging from 298.15 K to 318.15 K. 1HNMR and UV-visible analysis were carried out to investigate the solute- solvent interaction. Association constant for L-Leucine-BTBACl system as well as for L-Leucine-BTEACl system were evaluated to understand the diverse intermolecular interactions in the solution phase using UV-vis spectroscopy. Formation of thermodynamic background owing to different interactions occurring in the ternary mixtures were studied by evaluating the free energies of numerous molecular interactions. The source of various interactions is evaluated by calculating the apparent molar volume (ϕV), limiting apparent molar volume (ϕV0), viscosity Bcoefficients, molar refraction (RM), limiting molar refraction (RM0), molar conductivity (Λ) and surface tension (σ)volume, molar refraction, limiting molar refraction, viscosity B coefficients. Furthermore, adsorption energy, molecular electrostatic potential (MESP) maps and reduced density gradient (RDG) obtained by the application of density functional theory (DFT), have been used to determine the type of interactions which are consistent with the experimental observations. Chapter VII This chapter provides the detail analysis and application of supramolecular complexations of a very important antibiotic and a potential acetylcholine esterase inhibitor nitrofurantoin with α and β-cyclodextrins in aqueous medium. The molecular interactions have been investigated using 1HNMR spectroscopic studies, Job plot confirms the 1:1 stoichiometry of host with guest in the inclusion complexes. Binding constants for the formation of inclusion complexes have been determined using Benesi–Hildebrand method with the help of UV-visible spectroscopy. Free energy of binding of nitrofurantoin with cyclodextrins have been calculated from the binding constant value. This information subsequently determines the thermodynamic feasibility of the encapsulation process. PXRD and SEM studies further supports the inclusion complexes formation. Photo stability, CTDNA interaction studies of the inclusion complexes was carried out using UV-visible spectroscopy. Molecular docking study indicates the most preferable binding orientation of nitrofurantoin within the cavity of cyclodextrins. Chapter VIII This chapter contains the concluding remarks related the research works carried out in this thesis.Item Open Access Polydentate ligand based metal complexes for oxidase activity(University of North Bengal, 2023) Sahin Reja; Das, Rajesh KumarPolydentate ligands have been widely studied due to their ability to form stable and efficient metal complexes. In recent years, there has been growing interest in the use of these metal complexes as catalysts for various chemical reactions, including oxidase activity. Oxidases are enzymes that play a crucial role in biological processes such as cellular respiration and metabolism. The development of synthetic metal complexes with oxidase-like activity has the potential to provide alternative catalysts for these important processes. In this abstract, we discuss the design and synthesis of polydentate ligand based metal complexes for oxidase activity. We focus on the use of N, O-chelating ligands that have been shown to form stable and efficient metal complexes. The metal complexes are characterized using various spectroscopic techniques, and their oxidase activity is evaluated using a variety of assays. We also explore the mechanistic aspects of the oxidase activity of these metal complexes and compare their activity to that of natural oxidase enzymes. Overall, the results demonstrate the potential of polydentate ligand based metal complexes as efficient catalysts for oxidase activity. These complexes may provide a viable alternative to natural oxidase enzymes, and their development could lead to the development of new therapeutic agents and industrial catalysts. Polydentate ligands are molecules that possess multiple donor atoms capable of bonding with a central metal ion. Metal complexes of polydentate ligands have gained significant interest in recent years for their potential applications in various fields, including catalysis, drug design, and biotechnology. In particular, metal complexes of polydentate ligands have been shown to exhibit exceptional oxidase activity, making them an attractive candidate for various oxidation-based reactions. Oxidation is an essential process in biological systems, and the use of metal complexes of polydentate ligands in catalyzing oxidation reactions is a promising area of research. The oxidase activity of these metal complexes can be attributed to the presence of redox-active metal centers, which can donate or accept electrons during the oxidation process. The polydentate ligands stabilize the metal ion and enhance its reactivity, resulting in increased catalytic activity. The catalytic activity of polydentate ligand-based metal complexes for oxidase activity is dependent on several factors, including the types of metal ion, the coordination environment, and the ligand structure. The choice of metal ion plays a significant role in determining the catalytic activity of the complex. Transition metals such as copper, iron, and manganese have been extensively studied for their oxidase activity. These metals possess a variable oxidation state, allowing them to undergo redox reactions during the oxidation process. The coordination environment of the metal ion is another critical factor in determining the oxidase activity of the metal complex. The coordination environment influences the electron transfer properties of the metal ion, which in turn affects the catalytic activity of the complex. Ligands that provide a favorable coordination environment, such as chelating ligands, can enhance the catalytic activity of the complex. The structure of the polydentate ligand also plays a crucial role in determining the catalytic activity of the metal complex. The ligand structure can influence the binding affinity of the ligand for the metal ion, as well as the redox properties of the metal ion. Ligands with multiple donor atoms, such as bidentate and tridentate ligands, have been shown to exhibit excellent catalytic activity due to their ability to stabilize the metal ion. Polydentate ligand-based metal complexes have been shown to exhibit oxidase activity in various reactions, including the oxidation of alcohols, amines, and sulfides. These complexes can also catalyze the oxidation of organic compounds under mild conditions, making them attractive for industrial applications. The use of polydentate ligand-based metal complexes in the oxidation of biomolecules, such as DNA and proteins, is an exciting area of research that holds promise for various biotechnological applications. In conclusion, polydentate ligand-based metal complexes have shown exceptional oxidase activity, making them a promising candidate for various oxidation-based reactions. The catalytic activity of these complexes is dependent on several factors, including the choice of metal ion, the coordination environment, and the ligand structure. The use of these complexes in industrial applications and biotechnology holds significant promise and is an exciting area of research for the future. CHAPTER I Chapter I is an introductory one that describes polydentate ligand based metal complexes as efficient catalysts for oxidase activity and their applications in various fields as well as single crystals, their classification and methods of growth. Object and application of the present research work has also been outlined in this chapter. A brief description of the advantages of different type of technique of crystal growth was described. CHAPTER II Chapter II involves the experimental section briefly describing the chemicals and materials used in completing this research. This chapter also describes the novelty behind choice of organic linkers/ligands used in the works embodied in this thesis. This chapter also contains details of the physico-chemical and spectroscopic techniques, viz., single crystal, FTIR spectroscopy, NMR, and EPR, etc., used for the physicochemical characterization of the synthesized complexes. This chapter also describes the theoretical characterization (DFT, etc) of the hybrid complexes. CHAPTER III 2-(3-(Dimethylamino)propyl)isoindoline-1,3-dione (DAPID) has been synthesized and utilized to produce 3-(1,3-dioxoisoindolin-2-yl)-N,N-dimethyl propan-1-aminium perchlorate (DIDAP). Both DAPID and DIDAP were characterized using different spectroscopic techniques. Structure of the DIDAP has been determined using single crystal X-ray diffraction technique. DIDAP found to self assemble in a helical motif in its supramolecular structure with the aid of different hydrogen bonding, Cg···Cg and short interatomic contacts in the solid state. The compound DIDAP exhibited anticancer activity against the human hepatomas cell line (Hep G2) and the activity was further complemented by performing docking study. In addition, the computational studies have also been performed to examine the chemical reactivity of the compound. Shape index and Curvedness surfaces indicated -stacking with different features in opposed sides of the molecule. Fingerprint plot showed C···C contacts with similar contributions to the crystal packing in comparison with those associated to hydrogen bonds. Enrichment ratios for H···H, O···H and C···C contacts revealed a high propensity to form in the crystal. CHAPTER IV N1, N4- Bis(3-(dimethylamino)propyl)succinamide (DAPS) has been synthesized and utilized to produce 3,3'-[succinylbis(diazaneyl)]bis(N,N,N-trimethylpropan-1-ammonium) perchlorate (SAPAP). Both DAPS and SAPAP were characterized using different spectroscopic techniques. Structure of the SAPAP has been determined using single crystal X-ray diffraction technique. The compound SAPAP had excellent anticancer activity against the human colon carcinoma cell line (HT-29), proposing them as a suitable candidate for future anticancer therapies. Docking, Molecular dynamics simulation, pharmacokinetic predictions and ELISA were also employed to evaluate the inhibitory action of the synthesized compound against the said cancer cell line HT-29. CHAPTER V Keeping in mind the importance of oxidase activity it includes a versatile bioinspired metallocatalyst [Cu2L2(OAc)4] (L = 2-(3-(dimethylamino)propyl)isoindoline-1,3-dione), which has been synthesized and characterized as reported. To the best of our knowledge, a very few articles of paddlewheel type complexes have reported behave as catechol oxidase activity and phenoxazinone synthase activity. The EPR, CV, and ESI Mass analyses collectively support that the complex exhibits such activity via oxygen dependant enzymatic radical pathway. Furthermore, these activities are observed under fully aerobic conditions in which 3,5-di-tert-butylcatechol (3,5-DTBC) and 2-amino phenol (2-AP) are used as model substrates. Michaelis-Menten analysis derived from the pseudo first-order reaction kinetics established that this complex shows prominent catalytic activity towards 3,5- DTBC and 2-AP (Kcat 12.0726×103 h-1 and 6.6654×103 h-1). Molecular electrostatic potential (MEP) diagrams and density functional theory (DFT) reveals the charge density region within the complex while growth inhibition (GI50) and molecular docking study exposes substantial dose dependent anti-leukemic activity against Hep-G2 cell line. Moreover, promising anti-bacterial property was also detected on multi-drug resistant E. coli and B. cereus bacteria. CHAPTER VI In this chapter a promising bioinspired metallocatalyst [Cu(L1)2(L2)] (L1 = P-hydroxybenzoic acid, L2= N1,N1-dimethylpropane-1,3-diamine) has been produced and characterized in accordance with reports.. In the octahedron arrangement around the copper ion, the elongation along one axial direction and one equatorial direction results in a distorted geometry. Molecular assembly shows both inter and intra molecular H-bonding along with C-H---π interactions evident from the Hirshfeld surface analysis. The fingerprint plot discloses the relative contribution of percentage of intermolecular contacts (H⋯H, C⋯H and O⋯H) in the complex. To the best of our knowledge, no one has reported catechol oxidase activity and phenoxazinone synthase activity of Cu(II) complexes with P-hydroxy benzoic acid and propyl amine ligands so far. The EPR, CV, and UV analyses collectively support that the complex exhibits such activity via oxygen dependant enzymatic radical pathway. Furthermore, these activities are observed under fully aerobic conditions in which 3,5-di-tert-butylcatechol (3,5-DTBC) and 2-amino phenol (2-AP) are used as model substrates. Michaelis-Menten analysis derived from the pseudo first-order reaction kinetics established that this complex shows extremely high catalytic activity towards 3,5- DTBC and 2-AP (Kcat 1.729×105 h-1 and 0.260×105 h-1). The suggested mechanism has been supported by UV spectra data in which formation of hydrogen peroxide by observing the appearance of spectral band at λmax 353 nm indicates the active participation of molecular oxygen in the catalytic process. CHAPTER VII Future research in the field of polydentate ligand-based metal complexes with a focus on enhancing oxidase activity holds significant promise. These studies may lead to the development of novel ligands, versatile multifunctional complexes, and applications spanning biotechnology, medicine, energy conversion, and industrial processes, offering innovative solutions with broad-reaching implications for various fields.Item Open Access Exploration of the chelation property of few newly designed (N,O)-type schiff base ligands with d-block metals and bio-oxidase activities of their synthetic coordination compounds(University of North Bengal, 2023) Mahato, Shreya; Biswas, BhaskarThis dissertation comprises a total of seven chapters. Chapter I consists of a concise introduction to the design, foundation, and applications of the coordination compounds based on synthetic and commercially available ligands and the applicability of the present work in the recent trends of scientific development. Chapter II represents the synthesis, X-ray structural analysis, supramolecular architectures, and oxidative coupling of 2-aminophenol of a copper(II) complex, [Cu(L1)](H2O) (1) containing a previously reported Schiff base, H2L1 = 2,2'-((1,2- phenylenebis(azanylylidene))bis(methanylylidene))diphenol. The analysis of the crystal structure indicates that the Cu(II) centre adopts a square planar coordination geometry within the R3̅ space group. Furthermore, the aqua molecule located nearby actively participates in significant intermolecular hydrogen bonding, resulting in the formation of a water-mediated dimeric unit of the Cu(II) complex. The Hirshfeld surface analysis suggests that C−H…O and O−H…O types of hydrogen bonding, as well as π⋯π interactions play a crucial role. The catalytic properties of complex 1 were assessed for the oxidative dimerization of 2-aminophenol (2-AP) in methanol, revealing high catalytic efficiency with a kcat/KM value of 2.14×105. Additionally, studies utilizing mass spectrometry confirmed that the catalytic process involves the formation of an enzymesubstrate adduct in the solution phase. Chapter III represents the synthesis, X-ray structural analysis, Hirshfeld surface analysis, oxidative dimerization of 2-aminophenol and antibacterial activity of a newly designed copper(II)-Schiff base complex, [Cu(L2)2] (2), [Schiff base (HL2) = 2-(2- methoxybenzylideneamino)phenol]. X-ray analysis of complex 2 reveals that the Cu(II) complex forms crystals in a cubic crystal system with the Ia3̅ d space group. In its crystalline phase, the Cu(II) centre adopts a unique tetragonal bipyramidal geometry. Complex 2 has been tested for its phenaxozinone synthase activity in acetonitrile, mimicking biological systems, and demonstrated significant catalytic activity with a high turnover number of 536.4 h−1. Electrochemical analysis of complex 2 showed the appearance of two additional peaks at −0.15 and 0.46 V in the presence of 2-AP. This suggests the formation of AP−/AP•− and AP•−/IQ redox couples in the solution. The presence of the iminobenzosemiquinone radical at g = 2.057 was confirmed in the reaction mixture through electron paramagnetic resonance, indicating its role as the driving force for the oxidative dimerization of 2-AP. The ESI-mass spectrum exhibited a peak at m/z 624.81 for complex 2 in the presence of 2-AP, confirming that the catalytic oxidation proceeds through the formation of an enzyme-substrate adduct. Furthermore, complex 2 showed potential antibacterial properties against pathogenic bacterial species such as Staphylococcus aureus, Enterococcus, and Klebsiella pneumonia. Scanning electron microscope studies provided evidence that the antibacterial activity is attributed to the destruction of the bacterial cell membrane. Chapter IV represents the synthesis, crystal structure, supramolecular architecture, 4- methylcatechol oxidation, and bactericidal activity of an interesting zinc(II)-Schiff base complex, [Zn(L2)2Cl2] (3), [Schiff base (HL2) = 2-(2- methoxybenzylideneamino)phenol]. The analysis of the crystal structure of complex 3 indicates that the zinc centre is present in a distorted tetrahedral arrangement. The Schiff base molecule adopts three donor centres, but it becomes protonated and exists as a zwitterionic form, acting as a monodentate coordinator towards zinc. Complex 3 has been studied for its ability to catalyse the biomimetic oxidation of 4-methylcatechol (4-MC) in methanol, and it demonstrates high efficacy with a good turnover number of 1.45 × 103 h−1. Various techniques such as electrochemical studies and electron paramagnetic resonance analysis have been employed to investigate the behaviour of complex 3 in the presence of 4-MC. The results confirm that the catalytic reaction proceeds through enzyme-substrate binding, and the generation of radicals during the catalytic process drives the oxidation of 4-MC. Additionally, an antibacterial study has been conducted against several clinical pathogens including Bacillus sp, Enterococcus, and E. coli. To assess the antimicrobial properties of complex 3, scanning electron microscope and EDX analysis were performed on the pathogens treated with a low dosage of the complex. The results reveal the destruction of the bacterial cell membrane in the selected zone of inhibition area, with a zinc occurrence of 1.44%. This finding holds significant promise for the development of future antibacterial agents. Chapter V represents the synthesis and crystal structure of a palladium(II) complex [(κ4- {1,2-C6H4(N=CH−C6H4O)2}Pd] (4) supported by a dianionic salen ligand [1,2- C6H4(N=CH−C6H4O)2]2− (H2L1) was synthesized and used as a molecular pre-catalyst in the hydroboration of aldehydes and ketones. Complex 4 was evaluated as an effective catalyst in the hydroboration of aldehydes and ketones using pinacolborane (HBpin). This process yielded boronate esters in exceptional yields at room temperature without the need for solvents. Furthermore, complex 4 demonstrated its competence as a catalyst in the reductive amination of aldehydes with HBpin and primary amines. This reaction occurred under mild and solvent-free conditions, resulting in a high yield (up to 97%) of secondary amines. Both methodologies exhibited remarkable conversion rates, excellent selectivity, and a wide range of applicability, accommodating electron-withdrawing, electron-donating, and heterocyclic substituents. A computational investigation utilizing density functional theory (DFT) elucidated the reaction mechanism behind the complex 4-catalyzed hydroboration of carbonyl compounds in the presence of HBpin. Additionally, the protocols unveiled the dual functionality of HBpin in facilitating the hydroboration reaction. Chapter VI represents the design and preparation of metal complex salts of the novel hybrid d-f block type, [Cu(bpy)2]2[Ce(NO3)6]2 (5), [Cu(phen)2(NO3)]2[Ce(NO3)6](HNO3) (6), [Zn(bpy)2(NO3)][ClO4] (7), and [Zn(phen)2(NO3)]2 [Ce(NO3)6] (8); [bpy = 2,2'- bipyridine; phen = 1,10-phenanthroline]. X-ray analysis of the structures of 5 and 6 reveals that the copper(II) centres in the cationic complex units have highly distorted tetrahedral and rare bicapped square pyramidal coordination geometries, respectively. Similarly, 7 and 8 exhibits rare bicapped square pyramidal geometry for their zinc(II) ions, while 5, 6, and 8 contain cerium(IV) ions arranged in a dodecahedral geometry. Studying the supramolecular interactions, it is observed that intermolecular O⋯H and O⋯π short contacts contribute to binding the complex units in 5. In contrast, complex salt 6 demonstrates predominantly π⋯π interactions, along with O⋯H and O⋯π short contacts, which facilitate binding among the complex units. To investigate the chargetransport phenomenon, we utilized complex salts (5-8) to construct Schottky devices. The carrier mobilities (μ) for salts 5-8 were determined as 1.76 × 10−6, 9.02 × 10−6, 1.86× 10−8, and 4.31 × 10−8 m2 V−1 s−1, respectively, with corresponding transit times (τ) of 439, 85, 4.17 × 103, and 1.79 × 103 ns. These results indicate that complex salt 6 exhibits the highest transport properties among all the complex salts. Analysing the charge-transport properties from a crystal engineering perspective, the superior performance of 6 can be attributed to its predominant π⋯π interactions. Overall, the synthesis of these novel complex salts, along with their physicochemical properties and charge-transport applications, holds significant promise for the development of new crystalline materials with intelligent functionalities. Chapter VII outlines an overview of the progress made thus far and identifies prospective avenues for future research.Item Open Access Functional site mimics of few oxidase enzymes by newly developed coordination compounds with (N, N) and (N, O) donor ligands(University of North Bengal, 2023) Pal, Chanchal Kumar; Biswas, BhaskarDesign and synthesis of transition metal complexes with polydentate ligands and commercially available ligands is a significant field of research in Chemistry. Coordination compounds in coupling between transition metals and various ligands have drawn a great deal of interest to Chemist and Biologists for their remarkable structural features, biomimicking activities, catalytic activities, optoelectronic applications, magnetic materials, semiconductors, functional composites and different biological activities. Noteworthy, metal complexes that are the synthetic analogs of various metalloenzymes create significant progress in bioinspired chemistry with fascinating mechanistic perception of the catalytic cycles. Chapter I: This introductory chapter describes the design, synthesis and application of transition metal complexes based on Schiff base and commercially available ligands. It also states the catalytic and biological activities of metal complexes and the objectives of the present work. Chapter II: This chapter consists of the synthesis, catecholase, and phosphatase activity of an oxido-and acetate-bridged tetranuclear iron (III) cluster [Fe4 III(μ-O)2(μ- OAc)6(phen)2(H2O)2] (NO3)2(H2O)3 (1), [OAc = acetate; phen = 1,10-phenanthroline. Xray structural analysis of the compound reveals that all the Fe(III) centres in 1 adopt an octahedral coordination geometry and the tetra-iron(III) core exists in an unusual asymmetric conformation. The bond valence sum (BVS) calculation recommends the existence of all iron ions in the +3 oxidation level in the crystalline state. The tetra-iron(III) cluster elegantly catalyzes the oxidation of 3,5-di-tert-butylcatechol (DTBC) viz. Catecholase-like activity with a good turnover number, kcat 9.28102 h-1 in acetonitrile medium. Spectrophotometric titration exhibits two distinct isobestic points, which unanimously proves the rarely observed enzyme-substrate binding phenomenon in solution. Electrochemical analysis recommends the production of Fe(II)-semiquinone species in the catalytic oxidation of DTBC. Furthermore, the same iron(III) cluster displays phosphoester cleavage activity towards disodium salt of p-nitrophenylphosphate (PNPP) in an aqueousmethanol medium with a rate of 7.2010-4 m-1. ESI-MS measurements of tetra-iron(III) complex in the presence of PNPP recommend the formation of organophosphorous intermediate in solution and solvent aqua molecules probably make a nucleophilic attack to phosphorous centre favouring the generation of organophosphorous intermediate.Item Open Access Physicochemical studies of diverse interactions of some selected significant molecules prevalent in supramolecular and solution chemistry(University of North Bengal, 2023) Ghosh, Biswajit; Roy, Mahendra Nath; Dakua , Vikas KumarAs per the title of the thesis, I would like to show my deep insight into the field of Supramolecular Host-Guest Inclusion Complexation and the Amino Acid-Ionic Liquid interaction in aqueous medium. Supramolecular assembly has gained enormous significance these days in drug release due to their excellent bioavailability and remarkable ability to alter various properties of the drug such as its solubility, stability within the body, pharmacokinetics and pharmacodynamics. They also exhibit nontoxic properties, better encapsulation and controlled release. The spectroscopic contribution confirms the inclusion complexation of various bioactive molecules and their different photophysical properties in aqueous media. The inclusion phenomena can be satisfactorily expressed by UV-visible, 1H-NMR, FTIR, mass spectrometry and fluorescence emission spectroscopic studies. Surface tension, Powder XRD and SEM analysis provides a qualitative idea towards the formation of supramolecular assembly. The thermal stability of such assembly can be explained by TGA and DSC study. Theoretical molecular modelling studies of the supramolecular system confirm the data obtained from the experimental studies. The study of physicochemical properties of solutions provide significant knowledge on various thermodynamic properties of electrolytes and non-electrolytes, the effects of the variation in ionic constructions, mobility of ions along with their common ions. The genesis of diverse interactions between amino acids-ionic liquid in aqueous phase is usually exposed by measurement of the apparent molar volume ( v ), limiting apparent molar volume ( 0 v ), molar refraction ( M R ), limiting molar refraction ( 0 M R ), molar conductance (Ʌ), viscosity B coefficients obtained from different physicochemical methodologies. In this study, encapsulation of various biologically active molecules such as, Mephenesin, Riboflavin, 6-Propyl-2-thiouracil, have been investigated. These bioactive molecules have potential applications in living systems. Pharmacological activity is often considered to describe beneficial effects of bioactive molecules. Extensive studies on Nile blue and its derivatives have suggested that it could be potentially useful as fluorescent probes in this regard, because of their unique optical properties, excellent thermo and photostability, and low toxicity. In host–guest chemistry, the application of macrocyclic hosts in molecular recognition, controlled release of a drug and sensing field has received considerable interest. Incorporation of guest molecules in aqueous environment within the cavity of host molecules, e. g., α-cyclodextrin, β-Cyclodextrin or water soluble calixarene, provides the new insight into the molecular recognition (e. g. inclusion or complexation) through non-covalent interactions. Supramolecular host-guest chemistry gives a broad idea about the formation of inclusion complex between the host and the guest molecules. Hydrophobic cavities of host are capable of binding different guest molecules. In recent years, the whole supramolecular assemble has been vastly studied in many fields such as drug-delivery and analytical chemistry. Among the various host molecules, cyclodextrins and its derivative along with water soluble calixarene seems to be the most promising to form inclusion complexes, especially with various guest molecules with suitable dimension. Therefore, the primary objective of this thesis is to find out the influence of supramolecular recognition and solution chemistry that are inevitably significant because of their wide range of applications in many fields ranging from pharmaceutical to biomedical sciences. SUMMARY OF THE WORKS CHAPTER I This chapter contains the detail object of the research work, their scope and applications in the contemporary science. It also includes the reason of choosing the bioactive molecules, cyclodextrins, calix[4]arenes, ionic liquid, and the solvent systems. This chapter has a short list of all the methods of investigations used in the research work. CHAPTER II This chapter includes the review of the earlier works in this field of research done by various scientist and researchers across the world. This chapter also provides a detail theory of investigations, where the interacting forces among the molecules have been described. Here, the background theory of all the investigating methods, i.e., the theory of 1H-NMR, FTIR spectroscopy, UV-visible spectroscopy, Fluorescence spectroscopy, Mass Spectrometry, Differential Scanning Calorimetry, Thermogravimetric analysis, Scanning Electron microscopy, Powder XRD, Molecular docking study, Antimicrobial study, Cytotoxicity study, DNA and BSA binding study, Surface Tension, Conductivity, Density, Viscosity, Refractive Index have been discussed thoroughly and the significance of their use in the research work described in this thesis have been shown. CHAPTER III This chapter contains the experimental section. It covers the name, structure, physical properties, and applications of the biologically active molecules, cyclodextrins, calix[4]arenes, ionic liquid and solvents used in the research work. It also includes the details about the experimental methods, the descriptions and use of the instruments involved in the research work. CHAPTER IV This chapter comprises the experimental study emerged on the encapsulation of polyether compounds such as Mephenesin (MEP) into the nano hydrophobic cage of β-cyclodextrin as host molecule. The commonly known co-precipitation method was followed to prepare inclusion complex (IC) by molar ratio 1:1. Different spectrometric techniques e.g. transform infrared spectroscopy (FTIR), DSC, TGA, DTA, and scanning electron microscope (SEM) indicated molecular interactions between β-CD and MEP. UV-visible titration predicts the binding constant for βCD and MEP in solution state around 2.1×103M-1. The formation of the inclusion complex has been predicted by slight shifts in the FTIR as well as 1H NMR spectrum. Job plot and ESI-MS spectra showed that 1:1 inclusion complex has been formed. Molecular docking study unveils the inclusion mechanism which is well supported with the experimental data. In addition, UV-visible spectroscopic study predicts the binding interaction between Mephenesin with amino acid residues of BSA and DNA. *Published in the Journal of Molecular Liquids, 344, (2021) 117977 CHAPTER V This chapter consists of the formation of inclusion complex (IC) of an antithyroid drug 6-propyl-2- thiouracil (PTU) with α-cyclodextrin (α-CD) and to analyse its aqueous solubility, photostability, binding with Calf thymus DNA (CT-DNA), antibacterial and cytotoxic activities. The PTU-α-CD complex was synthesized by following the co precipitation method with a molar ratio of 1:1. The formed complex was characterized by employing several spectroscopic techniques such as 1H NMR, FTIR, DSC, TGA, powder XRD and SEM indicated the successful encapsulation of drug PTU into the nano cage of α-CD. The enhancement of thermal stability of PTU after complexation was shown by TGA and DSC analysis. Job’s plot confirmed the 1:1 molar ratio of guest (PTU) and host (α -CD) during the formation of IC and the molecular association constant as predicted between PTU and α-CD using UV-vis titration method was found to be 3297.57±0.15 M-1. The most desired orientation of the PTU molecule within the nonpolar binding pocket of α -CD cavity was speculated by molecular modelling study. The PTU- α -CD complex showed better in vitro antimicrobial activity results as compared to pure drug PTU. The aqueous solubility and photostability of PTU were greatly improved owing to the formation of the PTU- α -CD complex as shown using UV-vis spectroscopy. The PTU- α -CD complex (IC50 = 2.12 𝜇M) also displayed noteworthy in vitro cytotoxic activity than pure PTU (IC50 = 6.44 𝜇M) towards human kidney cancer cell line (ACHN) whereas (IC50 = 3.63 𝜇M) and (IC50 =2.09) 𝜇M) for PTU- α -CD and drug respectively in a normal kidney cell line (HEK-293). This research also predicts the release of PTU in presence of CT-DNA without any chemical alteration. Finally, these outcomes disclose that the complexation of PTU with α -CD could enhance the stability of PTU and display various applications associated with it. *Published in the Journal of Molecular Liquids, 380, (2023)121708 CHAPTER VI This chapter incorporates the construction of a supramolecular encapsulated complex between Nile blue (NB) and p-sulfonatothiacalix[4]arene (TSC4X). The developed inclusion complex (NB-TSC4X) was established by fluorescence spectroscopy, TGA, FTIR, 1HNMR, and DFT studies. Benesi- Hildebrand calculation showed a linear plot that indicated a 1:1 stoichiometric ratio having fairly high stability constant of 2720 M−1 in the solution phase. DFT analysis helps us to find out the optimized structure of the inclusion complex. Finally, the binding interaction of inclusion complex with bovine serum albumin (BSA) was evaluated. In brief, this work uncloses a new strategy to enhance the performance of fluorescent dye. *Communicated CHAPTER VII This chapter includes the solute–solvent interaction between ionic liquids (ILs) and amino acids (AA) in aqueous media plays a significant role for the optimization of a number of important biotechnological processes. L-Valine and L-Proline (two solute molecules) interact with an ionic liquid (Benzyltributylammonium chloride) in aqueous medium. Based on the different parameters such as apparent molar volume, viscosity B-coefficient, molar refraction, molar conductance, surface tension at different temperatures and different concentrations from density, viscosity, refractive index, conductance, surface tension measurements have been used to explain the molecular level interactions which was supported by NMR and UV-vis studies. Using Masson equation, the experimental slopes and the limiting apparent molar volumes are obtained which explain the solute-solute and solute-solvent interactions. Hepler’s technique and dB/dT values have been used to examine the structure-making and structure-breaking nature of the solutes in the solvents. Viscosity parameters, A and B obtained from Jones-Doles equation explained the solute-solute and solute-solvent interactions in the solution. Lorentz-Lorenz equation has used to calculate the molar refraction. The specific conductance and surface tension also explained the interaction properties. Further the findings have been supported by NMR study of the solutions and also considerable amount of theoretical analysis has been done which was in good agreement with the experimental result. The behavior of many other bio-molecules can be explained by considering amino acids as model and the mechanism has been extended to elucidate the behavior of other (biological) systems. In our findings we were emphasized on the nature of solute–solvent interactions and the presence of structural effect on the solvent in solution to analyze the molecular-level interactions prevalent in the systems. *Published in Fluid Phase Equilibria, 557, (2022) 113415 CHAPTER VIII This chapter includes the synthesis of a new encapsulated complex denoted as RIBO-TSC4X, that was derived from an important vitamin Riboflavin (RIBO) & psulfonatothiacalix[ 4]arene(TSC4X). The synthesized complex RIBOTSC4X was then characterized by utilizing several spectroscopic techniques such as 1HNMR, FT-IR, PXRD, SEM, and TGA. Job’s plot has been employed to show the encapsulation of RIBO (guest) with TSC4X (host) having a 1:1 molar ratio. The molecular association constant of the complex entity (RIBO-TSC4X) was found to be 3116.29±0.17 M-1, suggesting the formation of a stable complex. The augment in aqueous solubility of the RIBO-TSC4X complex compared to pure RIBO was investigated by UV-vis spectroscopy & it was viewed that the newly synthesized complex has almost 30 times enhanced solubility over pure RIBO. The enhancement of thermal stability upto 4400 C for the RIBO-TSC4X complex was examined by TG analysis. This research also forecasts RIBO’s release behaviour in the presence of CT-DNA, and at the same time, BSA binding study was also carried out. The Synthesized RIBO-TSC4X complex exhibited comparatively better free radical scavenging activity, thereby minimizing oxidative injury of the cell as evident from a series of antioxidant and anti-lipid peroxidation assay. Furthermore, the RIBO-TSC4X complex showed peroxidase-like biomimetic activity, which is very useful for several enzyme catalyst reactions. *Published in ACS Omega, 8,7, (2023) 6778-6790 CHAPTER IX This chapter includes the concluding remarks about the research works done in this thesis.Item Open Access Virtual screening, molecular docking studies admet properties dencity functional theory and 2D-QSar modeling to design potential inhibitors(University of North Bengal, 2023) Sarkar, Subhajit; Das, Rajesh KumarConventional drug design processes use trial and error methods for screening natural and synthetic compounds. It costs millions of dollars and very long time approximately 10-15 years. To meet these severe challenges nowadays pharmaceutical companies rely very much on computer-aided design techniques to discover potential drugs. Throughout the research work, various natural inhibitors that regulate a variety of physiochemical processes in bacteria and human beings have been studied. Derivatives of them have been designed and developed in such a way that they may be used as potent drugs producing no or minimal side effects and overcome the antibiotic resistance property. We hope, in silico drug design processes followed in different studies would save precious time and millions of dollars, leading to novel alternate therapeutics. CHAPTER I Microorganism including bacterium communicates among themselves through a unique mechanism called quorum sensing. The different QS pathways of Gram-negative and Gram-positive bacteria have been discussed elaborately in this chapter. Bacteria develop antibiotic resistance through various mechanisms among them biofilm formation is regulated by quorum sensing. Quorum sensing inhibitors (QSIs) interrupt the expression of virulence factors production and inhibit biofilm formation without killing bacteria or inhibiting bacterial growth. The QSIs are of two types natural and synthetic. It includes a details study of different types of QSIs and inhibition mechanisms. Hamamelitannin (HAM) a phytochemical has the capability to inhibit Staphylococcus aureus agr QS system. Our approach is to modify HAM by incorporating an active functional group for better efficacy. We have followed the same in silico process in another study where the target protein was chosen as heat shock protein 90 rather known as HSP90 and found in all species ranging from bacteria to humans. Over expression of this client protein may lead to several refractory diseases including cancer, inflammation, neurodegeneration, and viral infection. It discussed the various roles and functions of HSP90 in the human body. Besides, we have performed quantitative structure activity relationship (QSAR) analysis in two different cases. Phophodiesterase-4 (PDE4) and lysine-specific demethylase 1 (LSD1) are two key proteins that regulate various physiochemical processes in humans. Over expression of PDE4 may lead to severe diseases including chronic obstructive pulmonary disorder (COPD), and cardiovascular disease whereas unregulated LSD1 may result in tumorigenesis, neurodegenerative disorders, viral infection, diabetes, fibrosis, and various types of cancers including prostate, gastric, breast, lung, and leukemia. Separate studies of QSAR on these two proteins help us to identify best-fitted designed molecules as potent inhibitors of the target proteins. Detailed information on both PDE4 and LSD1 is described here. CHAPTER II The major in silico techniques that are widely popular among researchers are molecular docking, density functional theory (DFT) calculation, molecular docking, molecular dynamics (MD) simulations, and absorption, distribution, metabolism, excretion, toxicity (ADMET) prediction. Collective use of all of the mentioned computer aided techniques is necessary to predict potential QS inhibitors. It includes methodologies of all of the above mentioned techniques in detail. CHAPTER III A set of 26 derivative compounds have been designed by incorporation of different active functional groups at various positions of hamamelitannin (HAM) shown here. All structures were optimized using Gaussian software. Gaussian outputs were used to perform molecular docking with the help of Autodock Vina software. Docking results of HAM with three target proteins of PDB ID 4AE5, 4G4K, and 2FNP exhibited the binding energy value of -6.7, -6.5 and -6.6 kcal/mol respectively. Out of 26 derivatives of HAM, 14 compounds have shown higher binding affinity than that of HAM. The above in silico studies concluded that 14 ligands could be developed as effective inhibitors of S. aureus biofilm formation and considered for in vitro and in vivo analysis. CHAPTER IV It includes the natural product oroidin (ODN) considered a potent inhibitor of heat shock protein 90 (Hsp90) and its derivatives had been designed by substituting various functional groups in the various position of five membered rings. A library of thirty nine derivatives was designed by introducing various functional groups such that amide, amine, phosphate, hydroxyl, fluorine, methoxy, and carboxylic acid in the active pharmacophore of oroidin. All the analyses expressed that seven analogues possessed better chemical activity and docking capabilities than that of the source molecule ODN. These seven computationally designed derivatives may be used as novel beneficial agents in various cancer therapies including breast, ovarian, colon, pancreas, liver carcinoma, and leukemia treatments, and could be considered to develop as effective anticancer drug candidates in the future. CHAPTER V Keeping in mind the importance of PDE4 inhibitors it includes a study where a quantitative structure-activity relationship (QSAR) modeling method was performed to develop a standard model on a dataset of sixty-six significant PDE4A inhibitors encompassing common scaffolds in pyrazolo-oxazine, and imidazo-pyridazine compounds. According to QSARINS software, the model comprises three descriptors namely MoRSEM11, MoRSEP26and MoRSEC11 were found to be the best ones. The three descriptor model which was employed to predict pIC50 values as the studied response exhibited good R2 (0.8185), and F (73.658) values. Internal validation parameters Q2loo= 0.7845, Q2LMO= 0.7771and external validation parameters Q2F1= 0.8277, Q2F2= 0.8246, Q2F3= 0.8626, confirmed the stability and robustness of the developed model. On the basis of this model equation, pIC50 values of thirty-nine designed compounds were calculated. The potent lead molecules, predicted from the QSAR model, were further investigated by performing in silico approaches such as molecular docking, molecular dynamics simulation, bioavailability assessments, and toxicity prediction. The study revealed that the eight compounds possessed potent PDE4A inhibitory activity and might be considered as future drugs subject to the viability of in situ and in vivo proceedings. CHAPTER VI In this chapter quantitative structure activity relationship (QSAR) model was built from a dataset of 44 compounds as LSD1 inhibitors. The best 10 compounds have fully satisfied all the criteria of drug-like properties and these designed lead molecules would have more potency to treat LSD1 target after going through in vivo and in vitro analysis. CHAPTER VII 3D-QSAR analysis and application of ANN validation in CADD to design potential inhibitors of many critical diseases in future.Item Open Access Metal-free and Transition Metal Complex Mediated Synthetic Approaches towards the Development of Bioactive Compounds(University of North Bengal, 2023) Mahato Rajani Kanta; Biswas BhaskarBioactive compounds are found in mainly plants kingdom, fruits, vegetables, whole grains and various oil seeds. These compounds are secondary metabolites and provide the good health benefits from ancient times. Therefore, both laboratory and industrial synthetic chemists around the globe became extremely interested in the synthesis of these valuable compounds. Biomimics is a very popular protocol for the synthesis of pharmaceutically important compounds where transition metal complexes have been employed to produce the value-added products day by day. Due to the economic and environmental sustainability the metal-free, additive-free synthetic method has become a promising alternative which gained great interest in the recent decades. Chapter I: This is an introductory chapter of my thesis. Here, the importance of the transition metal complex and bioactive compounds are discussed along with the objectives of the present study. Chapter II: This chapter deals with the the synthesis, structural description, bio-mimics of phenazine oxidase activity and in-vitro antibacterial as well as antiproliferative activity of mononuclear aurum(III) complex, [Au(bpy)Cl2]NO3 (Complex 1) [bpy = 2,2'-bipyridine]. The crystal structure analysis of Complex 1 reveals that Au(III) centre adopts a nearly perfect square planar geometry and theoretical calculations agree well with the structural features. Examination of the catalytic fate for Au(III) complex towards oxidative coupling of o-phenylenediamine (OPD) in acetonitrile displays a good catalytic activity with a high turnover number, kcat = 6.75×102 h-1. The cytotoxic effect of complex 1 against the human lung cancer cell line (A549) is assessed through changes in morphologies observed in different fluorescent staining methods as well as MTT assay. The experimental outcomes ensure that most of the cell destruction of A549 occurs by apoptosis mode. The antibacterial activity of complex 1 against pathogenic bacteria is examined through the nature of variation in mitochondrial trans-membrane potential and depolarization pattern which suggests that destruction of mitochondrial membrane drives the development of antibacterial properties. Chapter III: In this chapter, we demonstrate the synthesis, structural characterization, computational studies and bio-mimics of the phenazine oxidase activity of a newly designed cobalt(III) complex, [Co(dpa)(dpa-H+)(N3)2]Cl2 (complex 2) [dpa = 2,2'- dipyridylamine] under an aerobic condition. The crystal structure analysis reveals that the cobalt(III) centre adopts an octahedral geometry and the complex forms a beautiful supramolecular frameworks through non-covalent interactions. The cobalt(III) catalyst turns out to be a promising catalyst for the oxidative coupling of o-phenylenediamine (OPD) in oxygen-saturated methanol with an excellent turnover number, kcat = 7.85×103 h-1. Spectrophotometric, electrochemical, mass spectrometry and computational analysis ensure that the course of catalysis undergoes through a catalyst-substrate complexation, facilitating the development of cobalt-iminobenzoquinone species in the solution. The computational calculations employing the density functional theory (DFT) throw a light on the mechanistic insights of the phenazine oxidase mimics. ETS-NOCV plots of the reactive intermediates portray the coordination-driven depletion of electron density from the nitrogens of OPD to the cobalt centre leading to the enhancement of electrophilic character on para-positioned C-atoms with respect to N-atoms of OPD, thereby catalysing the nucleophilic attack by second OPD to produce the oxidation product, 2,3-diaminophenazine (DAP). Interestingly, we are able to isolate the oxidation product of the OPD oxidation reaction as a hydrated chloride salt, DAPH+Cl- .3H2O (2). The crystal engineering perspectives of 2 attribute the intriguing fate of the secondary chlorides to the stabilization of the oxidation product in the crystalline phase. Chapter IV: This chapter highlights the phenazine scaffolds which are the versatile secondary metabolites of bacterial origin. It functions in the biological control of plant pathogens and contributes to the producing strains‟ ecological fitness and pathogenicity. In light of the excellent therapeutic properties of phenazine, we have synthesized a hydrated 2,3-diaminophenazinium chloride (DAPH+Cl- .3H2O) through direct catalytic oxidation of o-phenylenediamine with a cobalt(III) complex, [Co(dpa)(dpa-H+)(N3)2]Cl2 (complex 2) [dpa = 2,2'-dipyridylamine] in ethanol under aerobic condition. The crystal structure, molecular complexity and supramolecular aspects of DAPH+Cl- were confirmed and elucidated with different spectroscopic methods and single crystal X-ray structural analysis. Crystal engineering study on DAPH+Cl- exhibits a fascinating formation of (H2O)2…Cl-…(H2O) cluster and energy framework analysis defines the role of chloride ions in the stabilization of DAPH+Cl-. The bactericidal efficiency of the compound has been testified against a few clinical bacteria like Streptococcus pneumoniae, Escherichia coli, and K. pneumoniae using the disc diffusion method and the results of the high inhibition zone suggest its excellent antibacterial properties. The phenazinium chloride exhibits a significant percentage of cell viability and a considerable inhibition property against SARS-CoV-2 at non-cytotoxic concentration compared to remdesivir. Molecular docking studies estimate a good binding propensity of DAPH+Cl- with non-structural proteins (nsp2 and nsp7-nsp-8) and the main protease (Mpro) of SARS-CoV-2. The molecular dynamics (MD) simulation studies attribute the conformationally stable structures of the DAPH+Cl- bound Mpro and nsp2, nsp7-nsp8 complexes as evident from the considerable binding energy values, –19.2±0.3, –25.7±0.1, and –24.5±0.7 kcal/mol, respectively. Chapter V: This chapter addresses a metal-free methodology for the synthesis of 1,2-disubstituted and 2-substituted benzimidazoleswith high to excellent yields has been developed. The course of synthesis involves easy work-up, straightforward purification, inexpensive reaction setup, and wide substrate scope under extremely mild and operationally simple conditions which makes the synthetic strategy more lucrative, practical and reliable. The serious challenge to carry out these reactions in a pure aqueous medium has been achieved at 75 °C in the presence of air bubbles. The applicability of this operationally simple and metal-free synthetic approach for the gram-scale synthesis of benzimidazole derivatives with good yield (~74%) further strengthens its potentiality for synthesis at an industrial scale. Chapter VI: Here, we report the solvent-free green synthesis of two Schiff bases, (E)-2-((2-hydroxy-3-methoxybenzylidene)amino)-4-methylphenol (H2L1) and (E)-2-((2-hydroxybenzylidene) amino)-4-methylphenol (H2L2), and their inclusion complexes with β-cyclodextrin (β-CD). The encapsulation phenomenon, structural characteristics and hydrolytic stabilities of the H2L1, H2L2 and their inclusion complexes are determined with a suite of spectroscopic, analytical and crystallographic analyses. Dose and time-dependent cytotoxicity study of H2L1-β-CD and H2L2-β-CD against two breast cancer cell lines, Michigan Cancer Foundation-7 (MCF-7) and Metastatic mammary adenocarcinoma1 (MDA-MB-231), exhibit excellent inhibitory activity with significant non-cytotoxic concentrations and ensure a multifold elevation of bio-potency than the parent Schiff base compounds. The annexin-V assay determines the efficacy of these inclusion complexes to trigger apoptosis, suggesting that H2L2-β-CD possesses better efficacy as an anti-cancer drug. To the best of our knowledge, we, for the first time, report the inclusion of nanocrystalline Schiff bases into β-CD for multifold enrichment of bio-potency. Page | iv Chapter VII: Finally, this chapter has defined the conclusion outlook and the future range of the research endeavour.Item Open Access Explorative studies towards the synthesis of biocogically active carbocyclic and heterocyclic systems(University of North Bengal, 2023) Kundu Tandra; Ghosh PranabBeginning from the summer days of 2018, it took nearly five long years for me to finish the research work incorporated in this thesis entitled “EXPLORATIVE STUDIES TOWARDS THE SYNTHESIS OF BIOLOGICALLY ACTIVE CARBOCYCLIC AND HETEROCYCLIC SYSTEMS”. The work is mainly focused on development of efficient and environment benign methodologies for the synthesis of carbocyclic and heterocyclic compounds. The entire work depicted in this thesis has been divided into five chapters. In the beginning, Chapter I deals with a brief review on the development of novel reaction protocols for the transformation reaction on carbocyclic and heterocyclic compounds. These compounds have extensively been used in the designing of various pharmaceutically significant compounds. Apart from this, they are considered to be powerful building blocks for the construction of biologically active compounds. In Chapter II bio-based, environmental benign media ethyl lactate was used in synthesis of verities of unsymmetrical azobenzenes. The methodology proceeds without the use of toxic transition metal catalyst and avoids harsh reaction conditions. A green methodology is thus reported with synthesis of good yield of the product. In Chapter III a very simple, efficient and environment benign protocol for the synthesis of diverse array of 2,3-dihydroquinazolin-4(1H)-ones using wide range of aldehydes, isatoic anhydride with ammonium acetate was described. Eucalyptol, a bio-degradable solvent was used in this methodology which itself acted as a catalyst thus avoiding the use of toxic metals or hazardous materials. The activity of this bio-based reaction medium, eucalyptol was further extended towards the synthesis of isoxazolone derivatives using wide range of aldehydes, ethyl acetoacetate and hydroxyl amine hydrochloride. In Chapter IV synthesis of 1-amidoalkyl-2-naphthol and 1-thioamidoalkyl-2-naphthol is discussed. These derivatives carry great importance now a day as because they can easily be transformed to biologically potent heterocyclic entities via hydrolysis of amidic groups. In this chapter humic acid has been explored as catalyst with the association of operational simplicity of the method, mild reaction conditions, shorter reaction time. By this process, good yield of desired product 1-amidoalkyl-2-napthol is obtained by using aldehyde, β- napthol and acetamide. And 1-thioamidoalkyl-2-napthol is also prepared by using aldehyde, β-napthol and thioacetamide. In Chapter V inexpensive, environmental benign catalyst boric acid was used in synthesis of verities of bis-lawsones. The methodology proceeds without the use of toxic metal catalyst and avoids harsh reaction conditions. A green methodology is thus reported with synthesis of good yield of the product by reacting lawsone with wide range of aldehydes.