| Titre : | Etude par la modélisation moléculaire de la réactivité chimique et l’activité biologique de quelques composés organiques |
| Auteurs : | Halima Hazhazi, Auteur ; Youcef Boumedjane, Directeur de thèse |
| 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, 2018 |
| Format : | 1 vol. (86 p.) / 30 cm |
| Langues: | Français |
| Langues originales: | Français |
| Mots-clés: | 1,3-Dipolar reaction,Regioselectivity,Stereoselectivity,Effect of solvent,Conceptual DFT,2,4,5-tetrazine,QSAR,MLR. |
| Résumé : |
The objective of the present thesis is the theoretical study of some organic compounds, which is divided into two different applications: i) 1,3-dipolar cycloaddition reaction of methyl crotonate with 2,3,4,5 tetrahydropyridine l-oxide for interpretation and prediction the regio and stereoselectivity by means of several theoreticalapproaches, namely, the transition state theory state (TST) - Theory of frontier molecular orbital(FMO) - Indices derived from conceptual DFT. The findings obtained in this work are in agreement with experimental data ii) QSAR studies have been carried out on eighteen molecules of 1,2,4,5-tetrazine derivatives, firstly we have analyzed the molecular reactivity of 1,2,4,5-tetrazine by conceptual DFT. Also, multiple linear regression (MLR) procedure was used to find the correlation between chemical descriptors and antitumor activity of 1,2,4,5-tetrazine derivatives and the leave-one-out (LOO) method to estimate the predictivity of our models. High correlation between experimental and predicted of the activity values was observed, indicating the validation and the good quality of the derived QSAR models. |
| Sommaire : |
LIST OF ABBREVIATIONS …………………………………………………………… I LIST OF TABLES ……………………………………………………………………… III LIST OF FIGURES & SCHEMAS………………………………………………………. IV General Introduction General Introduction…………………………………………………………………… 02 References……………………………………………………………………………… 06 Chapter I Quantum methods in chemistry I.1. Introduction……………………………………………………………………….... 09 I.2. Theoretical basis…………………………………………………………………… 10 I.2.1. Schrödinger equation…………………………………………………………. 10 I.2.2. Born-Oppenheimer Approximations…………………………………………. 10 I.2.3. Hartree-Fock approximation…………………………………………………. 11 I.3. Density-functional theory (DFT)…………………………………………………… 12 I.3.1. Hohenberg and Kohn theorems……………………………………………….. 12 I.3.2. Kohn-Sham theorems…………………………………………………………. 14 I.3.3. Exchange-correlation (XC) functional……………………………………….. 15 I.3.3.1. Local density approximation (LDA)…………………………………… 16 I.3.3.2. Generalised Gradient Approximation (GGA)………………………….. 17 I.4. Hybrid functional…………………………………………………………………... 18 I.5. Basis sets…………………………………………………………………………… 19 I.6. solvatation methods………………………………………………………………… 20 I.7. Comprarison between HF and DFT…… ………………………………………….. 22 I.8. References………………………………………………………………………….. 24 Chapter II Theoretical study of the regio- and stereoselectivity of the 1,3-DC reaction of 2,3,4,5- tetrahydropyridine-l-oxide with methyl crotonate II.1. Introduction……………………………………………………………………….. 28 II.2. 1,3-Dipolar cycloaddition reactions………………………………………….......... 30 II.2.1. The 1,3-dipole…………………………………………………………… .… 30 II.2.2. The dipolarophile…………………………………………………………… 32 II.3. Mechanistic aspects……………………………………………………………….. 33 II.4. Regioselectivity……………………………………………………………………. 34 II.5. Stereoselectivity…………………………………………………………………… 35 II.6. Theoretical analysis of 1,3-dipolar cycloaddition reactions……………………….. 36 II .6.1. Frontier molecular orbital theory and Sustmann classification…………… 36 II.6.2. Transition state theory (TST)……………………………………………… 37 II.6.3. Chemical Reactivity Indexes……………………………………………… 38 II.6.3.1.Global properties…………………………………………………... 39 II.6.3.1.1. Electronic chemical potential…………………………... 39 II.6.3.1.2. Chemical hardness……………………………………… 40 II.6.3.1.3. Electrophilicity………………………………………….. 41 II.6.3.1.4. Nucleophilicity………………………………………….. 41 II.6.3.2. Local properties…………………………………………………… 42 II.7. Materials and methods……………………………………………………………… 43 II.8. Results and Discussion………………………………………………………........... 44 II.8.1. Regiochemistry study based on FMO and reactivity indices…………........... 44 II.8.2. Mechanistic study of the cycloaddition reaction based on activation energy.. 49 II.8.2.1. Energies of the Transition Structures………………………………..... 49 II.8.2.2. Geometry analysis…………………………………………………….. 53 II.9. Conclusion…………………………………………………………………………. 54 II.10. References………………………………………………………………………… 55 Chapter III DFT-based reactivity and QSAR modeling of 1,2,4,5-tetrazine inhibitors III.1.Introduction………………………………………………………………………. 60 III.2. Objectives of QSAR…………………………………………………………....... 61 III.3. Molecular Descriptors………………………………………………………......... 62 III.3. 1. Constitutional descriptors……………………………………………….. 62 III.3. 2. Topological descriptors…………………………………………………. 62 III.3. 3. Electrostatic descriptors………………………………………………… 62 III.3. 4. Geometrical descriptors………………………………………………… 63 III.3. 5. Quantum chemical descriptors………………………………………….. 63 III.4. Biological Parameters……………………………………………………………. 63 III.5. Statistical methods……………………………………………………………….. 64 III.5.1.Multiple linear regression………………………………………………… 65 III.6. Chemometric Tools………………………………………………………………. 65 III.6. 1. Determination coefficient (R2)…………………………………………... 65 III.6. 2. Adjusted R2 ()………………………………………………………… 66 III.6. 3.Variance ratio (F)………………………………………………………… 66 III.6. 4.Standard error of estimate (s)…………………………………………….. 67 III.7. Validation of QSAR Models…………………………………………………….... 67 III.8. Material and methods……………………………………………………………... 69 III.8.1. Computational methods………………………………………………….. 69 III.8.2. QSAR modeling………………………………………………………….. 70 III.9.Results and discussion…………………………………………………………….. 70 III.9.1. Analysis of the DFT reactivity indices of 1,2,4,5-tetrazine……………... 70 III.9.2. Study of Quantitative structure-activity relationship (QSAR) for 1,2,4,5 - tetrazine derivatives…………………………………………………………………….. 73 III.10. Conclusion………………………………………………………………………. 79 III.11. References……………………………………………………………………….. 80 General conclusion……………………………………………………………………... 85 Appendix……………………………………………………………………………….. 88 |
| En ligne : | http://thesis.univ-biskra.dz/id/eprint/3878 |
Disponibilité (1)
| Cote | Support | Localisation | Statut |
|---|---|---|---|
| TCH/63 | Théses de doctorat | bibliothèque sciences exactes | Consultable |
