Titre : | Theoretical study of the physicochemical properties of heterocyclic pharmaceutical interest |
Auteurs : | Lazhar BOUCHLALEG, Auteur |
Type de document : | Thése doctorat |
Editeur : | Biskra [Algérie] : Faculté des Sciences Exactes et des Sciences de la Nature et de la Vie, Université Mohamed Khider, 2016 |
Format : | 1 vol. (138 p.) / ill.couv.ill.en coul / 30cm |
Langues: | Anglais |
Langues originales: | Anglais |
Résumé : |
In this work a fundamental and original research was made on the molecule of Hydantoin heterocyclic, the aim is to predict the reactivity and biological activity studied of the compound. The structural parameters, electronics and vibrational frequencies of Hydantoin at the ground state have been calculated by using, PM3, ab initio/HF and DFT/B3LYP methods. The optimized geometrical parameters are in good agreement with experimental values. Comparison of the obtained fundamental vibrational frequencies of Hydantoin result by DFT/B3LYP (6-311G++ (d, p)) method, are in a close agreement with the experimental data. The nature of substituent affects the electronic and energy parameters of basic core of Hydantoin. Also indeed, this qualitative and quantitative study allows us to predict the chemical reactivity of derivatives of Hydantoin. |
Sommaire : |
Remerciements …………………………………………………………................................ Aknowledgements........................................................................................................... List of tables…………………………………………………………………………….……...... List of figures……………………………………………………………………………..…....... Listings diagrams……………………………………………………………………….……...... List of Abbreviations…………………………………………………………………………..... Contents………………………………………………………………………………….…........ I-General introduction………………………………………………………………….…....... CHAPTER I…………………………………………………………………………………..... BIOLOGY AND APPLIED PHARMACEUTICAL BY USES CHEMISTRY SYNTHESIS OF HYDANTOIN............................................................................................... I.Introduction........................................................................................................................... 16 I.1. Biological Effects and Therapeutic Applications of Hydantoins......................................... 17 I.2 Hydantoin derivatives and their pharmacological use……………………………………...... 17 I.2.1 Physiological and biochemical role of hydantoins.......................................................... 17 I.2.2 Uses of Hydantoins…………………………………………………………………........... 18 I.2.2.a Pharmaceutical/Biological Properties........................................................................... 18 I.2.2.b Other Applications....................................................................................................... 21 I.2.3 Structure of hydantoin derivatives…………………………………………………............. 21 I.2.3.3 Methods of Synthesis……………………………………………………………..…........ 21 I.2.3.3.a Hydantoin Chemistry and Natural Occurrence........................................................ 21 I.2.3.3.b Hydantoins ........................................................................................ .................... 22 I.2.3.3.c Thiohydantoins ....................................................................................................... 23 I.2.4 Natural Occurrence of Hydantoins………………………………………………..….......... 23 I.3 Methods of Preparation ……………………………………………………………….......... 24 1.3.1 Classical Methods of Synthesis...................................................................................... 24 1.3.2 The Bucherer-Bergs Reaction………………………………………………………........... 25 I.3.2.1 Development................................................................................................................. 25 I.3.2.2 Mechanism of the Bucherer-Bergs Reaction................................................................. 26 I.3.2.3 Uses of the Bucherer-Bergs Reaction............................................................................ 27 I.4 Reactivity of Hydantoins……………………………………………………………….......... 29 I.4.1 Hydrolysis of Hydantoins................................................................................................ 29 I.4.2 N-Alkylation of Hydantoins............................................................................................ 31 I.4.3 Aldol-Type Reactions....................................................................................................... 31 I.5 The Strecker Reaction........................................................................................................ 32 I.6 Summary............................................................................................................................... 33 I. References................................................................................................................................ 34 CHAPTER II:THEORETICAL ASPECTS OF MODELING MOLECULAR II.1 Introduction.......................................................................................................................... 39 II.2 Geometry Optimization (EnergyMinimization).................................................................. 39 II.2.1 Molecular Modeling and Computational Chemistry............................................................ 40 II.2.2 Overview of Computational Chemistry Methods............................................................... 41 II.2.3 Molecular Mechanics(MM)................................................................................................ 41 II.2.4 Ab Initio Electronic Structure Methods............................................................................... 44 II.2.5 Wave function-based approaches expand the electronic..................................................... 44 II.2.6 Basic Quantum Mechanics (QM)...................................................................................... 44 II.2.7 The Hartree-Fock (HF) Self-Consistent Field Approximation............................................. 46 II.2.7.a Electron Correlation........................................................................................................ 47 II.2.7.b Configuration interaction............................................................................................... 48 II.2.7.c The coupled cluster(cc) methods and quadratic CI........................................................ 48 II.2.8 Density Functional Theory (DFT)..................................................................................... 49 II.2.8.a The local density approximation (LDA)......................................................................... 50 II.2.8.b The generalized gradient approximation (GGA)............................................................ 50 II.2.9 Semi-empirical Methods................................................................................................... 52 II.2.10 BasisSets......................................................................................................................... 56 II.3 Softwares Used..................................................................................................................... 59 II.3.1 ChemDraw.......................................................................................................................... 59 II.3.2 GaussView.......................................................................................................................... 59 II.3.3 HyperChem ........................................................................................................................ 60 II. References................................................................................................................................ 62 2nd Part: Results and Discussion Figure organizational work Chapter III In silico evaluation of Molecular Structure, Vibrational Spectra and Substitution Effect of Hydantoin III.1 Introduction........................................................................................................................... 66 III.2 Computational details............................................................................................................ 67 III.3 Results and discussion........................................................................................................... 67 III.3.a Molecular geometry of Hydantoin………………………………….…………............... 67 III.3.b Vibration frequencies of Hydantoin................................................................................... 68 III.3.c Linear regression between frequencies 'νexp and νth'....................................................... 75 III.3.d Electronic properties of Hydantoin.................................................................................. 76 III.3.e Substituent effects on the electronic structure in Hydantoin and derivatives................... 78 III.4 Conclusions.......................................................................................................................... 89 III.References.............................................................................................................................. 90 CHAPTER IV: Quantitative Structure Activity Relationship Study for Development of Plasmin Inhibitors Controlled by the Spacer Hydantoin IV.1. Introduction........................................................................................................................ 93 IV.2. Materials and methods…………………………………………………………….............. 95 IV.2.1. Experimental details…………………………………………………………….............. 95 IV.2.2.Descriptors generation...................................................................................................... 95 IV.2.3. Regression analysis.......................................................................................................... 96 IV.3. Results and discussion…………………………………………………………….............. 96 IV.3.1. Structure-Physicochemical Property Relationships......................................................... 96 IV.3.2. Quantitative Structure-Activity Relationships Studies……………............................... 100 IV.4 QSAR Theoretical and Multi-Parameter Optimization (MPO)........................................... 104 IV.5 Conclusion........................................................................................................................... 107 IV.References............................................................................................................................. 108 General conclusion....................................................................................................... ANNEX I 114 ANNEX II 124 Publications Abstract (Arabic, English and French) |
En ligne : | http://thesis.univ-biskra.dz/2475/1/Th%C3%A8se_2016.pdf |
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Cote | Support | Localisation | Statut |
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TCH/41 | Théses de doctorat | bibliothèque sciences exactes | Consultable |