|
| Titre : |
“Synthesis, Biological Activities Evaluation, Density Functional Theory Investigation, and Molecular Docking studies of Hydroxybutyl and Hydroxypropyl Aminophosphonic Acids” |
| Type de document : |
document électronique |
| Auteurs : |
Anis Bouchama, Auteur ; Abdelkader Hellal, Directeur de thèse |
| Editeur : |
Sétif:UFA1 |
| Année de publication : |
2026 |
| Importance : |
1 vol (220 f.) |
| Format : |
29 cm |
| Langues : |
Anglais (eng) |
| Catégories : |
Thèses & Mémoires:Chimie
|
| Mots-clés : |
α-Aminophosphonic acids
Organophosphonates
Antioxidant activity
Density Functional Theory (DFT)
Molecular docking
ADME-T |
| Index. décimale : |
204- chimie |
| Résumé : |
This PhD thesis focuses on the design, synthesis, and evaluation of new α-aminophosphonic acids (HAP1 and HAP2) as promising bioactive compounds. It begins with a comprehensive review of organophosphonates, emphasizing their importance in medicinal chemistry due to the stability of the carbon–phosphorus (C–P) bond, which allows them to mimic biological phosphates and act as enzyme inhibitors. The experimental work involves the synthesis of the target compounds, followed by their characterization using techniques such as FT-IR, UV-Vis, and NMR spectroscopy. In addition, computational studies based on Density Functional Theory (DFT) and molecular docking were conducted to understand their structural, electronic, and biological interactions, alongside ADME-T predictions to evaluate their pharmacokinetic and toxicity profiles. The biological investigations demonstrated that the synthesized compounds exhibit significant antioxidant activity, supported by multiple assays (DPPH, ABTS, FRAP), as well as synergistic effects when combined with standard antioxidants. Furthermore, they showed antibacterial properties and enzyme inhibition potential. A key innovation of this work lies in the incorporation of these compounds into hyaluronic acid-based nanohydrogels, enabling controlled drug release, improved stability, and enhanced bioavailability. Overall, this study highlights the potential of α-aminophosphonic acids as valuable candidates in pharmaceutical development, particularly when integrated with nanotechnology-based delivery systems. |
| Note de contenu : |
Sommaire
Table of contents
General Introduction .............................................................................................................. 1
I Bibliographic Review .................................................................................................... 7
I.1 Introduction ........................................................................................................... 7
I.2 Historical Overview and Classification of Phosphonates ...................................... 8
I.2.1 Historical Development ..................................................................................... 8
I.2.2 Structural Diversity and Nomenclature ........................................................... 10
I.3 Synthetic Strategies for Organophosphonates ..................................................... 11
I.3.1 Classical Reactions .......................................................................................... 11
I.3.2 Modern Reactions ............................................................................................ 13
I.3.3 Characterization and Purification .................................................................... 20
I.4 Biological Activities ............................................................................................ 20
I.4.1 Enzyme Inhibition ........................................................................................... 20
I.4.2 Antimicrobial Properties.................................................................................. 20
I.4.3 Antiviral Activity ............................................................................................. 23
I.4.4 Anticancer Potential ........................................................................................ 25
I.4.5 Anti-inflammatory Effects ............................................................................... 27
I.4.6 Antioxidant Properties ..................................................................................... 28
I.5 Agricultural Applications .................................................................................... 29
I.6 Density Functional Theory (DFT) and Computational Insights .......................... 30
I.6.1 DFT Applications in Organophosphonates Research ...................................... 30
I.6.2 Docking Studies of Phosphonates ................................................................... 30
I.6.3 Importance of Early ADME-T Assessment..................................................... 30
I.6.4 Integrating ADME-T with Design ................................................................... 31
I.7 Nano Drug Delivery of Organophosphonates ..................................................... 31
I.8 Somes of Nanodrug Delivery Systems Suitable for Organophosphonates ......... 32
I.8.1 Polymeric Nanoparticles .................................................................................. 32
I.8.2 Liposomes ........................................................................................................ 33
I.8.3 Nanohydrogels ................................................................................................. 33
I.8.4 Hyaluronic Acid-Based Nanocarriers .............................................................. 34
I.9 Challenges, Limitations, and Future Directions .................................................. 34
I.9.1 Synthetic Complexity and Cost ....................................................................... 34
I.9.2 Computational Accuracy and Validation ........................................................ 34
I.9.3 Translating In Vitro to In Vivo ........................................................................ 35
I.9.4 Emerging Fields ............................................................................................... 35
I.10 Conclusion ........................................................................................................... 35
II Materials and Methods ................................................................................................ 38
II.1 Introduction ......................................................................................................... 38
II.2 Materials .............................................................................................................. 38
II.2.1 Chemicals and Reagents .............................................................................. 38
II.2.2 Equipment .................................................................................................... 45
II.2.3 Software Tools :........................................................................................... 47
II.3 Experimental Methods ......................................................................................... 51
II.3.1 Synthesis of Organophosphonates ............................................................... 51
II.3.2 Density Functional Theory (DFT) Studies .................................................. 52
II.3.3 Molecular Docking ...................................................................................... 54
II.3.4 ADME-T and Drug-likeness Predictions .................................................... 56
II.4 Nanoparticle investigation ................................................................................... 57
II.4.1 Nanohydrogel preparation ........................................................................... 57
II.4.2 Loading Efficiency (Drug Loading ) ........................................................... 58
II.4.3 In Vitro Release Testing .............................................................................. 59
II.5 Bilogicals assay ................................................................................................... 61
II.5.1 ABTS Scavenging Activity ......................................................................... 61
II.5.2 DPPH free radical ........................................................................................ 62
II.5.3 Phenanthroline-Ferric Reducing Power Assay ............................................ 64
II.5.4 Ferric Reducing Power (FRP) Assay........................................................... 65
II.5.5 Antibacterial assay ....................................................................................... 65
II.6 Conclusion ........................................................................................................... 66
III Synthesis and Evaluation of Organophosphonates .................................................. 71
III.1 Introduction ......................................................................................................... 71
III.2 Synthesis method ................................................................................................. 71
III.2.1 Synthesis of α-Aminophosphonic Acids (HAP1 and HAP2) ....................... 72
III.3 Preliminary Characterization: Solubility, Melting Points, and TLC ................... 75
III.3.1 Solubility Test.............................................................................................. 75
III.3.2 Melting Points.............................................................................................. 78
III.3.3 Thin-Layer Chromatography (TLC) Analysis ............................................. 78
III.4 Advanced Spectroscopic Analyses: IR, UV-Vis, and NMR ............................... 79
III.4.1 Fourier Transform Infrared Spectroscopy (FT-IR) ..................................... 79
III.4.2 Ultraviolet-visible (UV-Vis) Spectrophotometry ........................................ 81
III.4.3 Nuclear Magnetic Resonance (NMR) ......................................................... 82
III.4.4 Carbon13 Nuclear Magnetic Resonance (13C-NMR) ................................... 84
III.5 Conclusion ........................................................................................................... 86
IV Computational Approach using DFT ...................................................................... 89
IV.1 Introduction ......................................................................................................... 89
IV.2 Integrative DFT Analysis .................................................................................... 89
IV.2.1 Geometric Optimization .............................................................................. 89
IV.2.2 Mulliken Atomic Charges Analysis ............................................................ 91
IV.2.3 Dipole Moments .......................................................................................... 95
IV.2.4 Frontier Molecular Orbital Analysis ............................................................ 95
IV.2.5 Global Reactivity Descriptors ..................................................................... 96
IV.2.6 Molecular Electrostatic Potential Surface (MESP) ..................................... 98
................... |
| Côte titre : |
Dch/0042 |
| En ligne : |
https://repository.univ-setif.dz/server/api/core/bitstreams/87d1073b-aa6b-459e-8 [...] |
| Format de la ressource électronique : |
pdf |
“Synthesis, Biological Activities Evaluation, Density Functional Theory Investigation, and Molecular Docking studies of Hydroxybutyl and Hydroxypropyl Aminophosphonic Acids” [document électronique] / Anis Bouchama, Auteur ; Abdelkader Hellal, Directeur de thèse . - [S.l.] : Sétif:UFA1, 2026 . - 1 vol (220 f.) ; 29 cm. Langues : Anglais ( eng)
| Catégories : |
Thèses & Mémoires:Chimie
|
| Mots-clés : |
α-Aminophosphonic acids
Organophosphonates
Antioxidant activity
Density Functional Theory (DFT)
Molecular docking
ADME-T |
| Index. décimale : |
204- chimie |
| Résumé : |
This PhD thesis focuses on the design, synthesis, and evaluation of new α-aminophosphonic acids (HAP1 and HAP2) as promising bioactive compounds. It begins with a comprehensive review of organophosphonates, emphasizing their importance in medicinal chemistry due to the stability of the carbon–phosphorus (C–P) bond, which allows them to mimic biological phosphates and act as enzyme inhibitors. The experimental work involves the synthesis of the target compounds, followed by their characterization using techniques such as FT-IR, UV-Vis, and NMR spectroscopy. In addition, computational studies based on Density Functional Theory (DFT) and molecular docking were conducted to understand their structural, electronic, and biological interactions, alongside ADME-T predictions to evaluate their pharmacokinetic and toxicity profiles. The biological investigations demonstrated that the synthesized compounds exhibit significant antioxidant activity, supported by multiple assays (DPPH, ABTS, FRAP), as well as synergistic effects when combined with standard antioxidants. Furthermore, they showed antibacterial properties and enzyme inhibition potential. A key innovation of this work lies in the incorporation of these compounds into hyaluronic acid-based nanohydrogels, enabling controlled drug release, improved stability, and enhanced bioavailability. Overall, this study highlights the potential of α-aminophosphonic acids as valuable candidates in pharmaceutical development, particularly when integrated with nanotechnology-based delivery systems. |
| Note de contenu : |
Sommaire
Table of contents
General Introduction .............................................................................................................. 1
I Bibliographic Review .................................................................................................... 7
I.1 Introduction ........................................................................................................... 7
I.2 Historical Overview and Classification of Phosphonates ...................................... 8
I.2.1 Historical Development ..................................................................................... 8
I.2.2 Structural Diversity and Nomenclature ........................................................... 10
I.3 Synthetic Strategies for Organophosphonates ..................................................... 11
I.3.1 Classical Reactions .......................................................................................... 11
I.3.2 Modern Reactions ............................................................................................ 13
I.3.3 Characterization and Purification .................................................................... 20
I.4 Biological Activities ............................................................................................ 20
I.4.1 Enzyme Inhibition ........................................................................................... 20
I.4.2 Antimicrobial Properties.................................................................................. 20
I.4.3 Antiviral Activity ............................................................................................. 23
I.4.4 Anticancer Potential ........................................................................................ 25
I.4.5 Anti-inflammatory Effects ............................................................................... 27
I.4.6 Antioxidant Properties ..................................................................................... 28
I.5 Agricultural Applications .................................................................................... 29
I.6 Density Functional Theory (DFT) and Computational Insights .......................... 30
I.6.1 DFT Applications in Organophosphonates Research ...................................... 30
I.6.2 Docking Studies of Phosphonates ................................................................... 30
I.6.3 Importance of Early ADME-T Assessment..................................................... 30
I.6.4 Integrating ADME-T with Design ................................................................... 31
I.7 Nano Drug Delivery of Organophosphonates ..................................................... 31
I.8 Somes of Nanodrug Delivery Systems Suitable for Organophosphonates ......... 32
I.8.1 Polymeric Nanoparticles .................................................................................. 32
I.8.2 Liposomes ........................................................................................................ 33
I.8.3 Nanohydrogels ................................................................................................. 33
I.8.4 Hyaluronic Acid-Based Nanocarriers .............................................................. 34
I.9 Challenges, Limitations, and Future Directions .................................................. 34
I.9.1 Synthetic Complexity and Cost ....................................................................... 34
I.9.2 Computational Accuracy and Validation ........................................................ 34
I.9.3 Translating In Vitro to In Vivo ........................................................................ 35
I.9.4 Emerging Fields ............................................................................................... 35
I.10 Conclusion ........................................................................................................... 35
II Materials and Methods ................................................................................................ 38
II.1 Introduction ......................................................................................................... 38
II.2 Materials .............................................................................................................. 38
II.2.1 Chemicals and Reagents .............................................................................. 38
II.2.2 Equipment .................................................................................................... 45
II.2.3 Software Tools :........................................................................................... 47
II.3 Experimental Methods ......................................................................................... 51
II.3.1 Synthesis of Organophosphonates ............................................................... 51
II.3.2 Density Functional Theory (DFT) Studies .................................................. 52
II.3.3 Molecular Docking ...................................................................................... 54
II.3.4 ADME-T and Drug-likeness Predictions .................................................... 56
II.4 Nanoparticle investigation ................................................................................... 57
II.4.1 Nanohydrogel preparation ........................................................................... 57
II.4.2 Loading Efficiency (Drug Loading ) ........................................................... 58
II.4.3 In Vitro Release Testing .............................................................................. 59
II.5 Bilogicals assay ................................................................................................... 61
II.5.1 ABTS Scavenging Activity ......................................................................... 61
II.5.2 DPPH free radical ........................................................................................ 62
II.5.3 Phenanthroline-Ferric Reducing Power Assay ............................................ 64
II.5.4 Ferric Reducing Power (FRP) Assay........................................................... 65
II.5.5 Antibacterial assay ....................................................................................... 65
II.6 Conclusion ........................................................................................................... 66
III Synthesis and Evaluation of Organophosphonates .................................................. 71
III.1 Introduction ......................................................................................................... 71
III.2 Synthesis method ................................................................................................. 71
III.2.1 Synthesis of α-Aminophosphonic Acids (HAP1 and HAP2) ....................... 72
III.3 Preliminary Characterization: Solubility, Melting Points, and TLC ................... 75
III.3.1 Solubility Test.............................................................................................. 75
III.3.2 Melting Points.............................................................................................. 78
III.3.3 Thin-Layer Chromatography (TLC) Analysis ............................................. 78
III.4 Advanced Spectroscopic Analyses: IR, UV-Vis, and NMR ............................... 79
III.4.1 Fourier Transform Infrared Spectroscopy (FT-IR) ..................................... 79
III.4.2 Ultraviolet-visible (UV-Vis) Spectrophotometry ........................................ 81
III.4.3 Nuclear Magnetic Resonance (NMR) ......................................................... 82
III.4.4 Carbon13 Nuclear Magnetic Resonance (13C-NMR) ................................... 84
III.5 Conclusion ........................................................................................................... 86
IV Computational Approach using DFT ...................................................................... 89
IV.1 Introduction ......................................................................................................... 89
IV.2 Integrative DFT Analysis .................................................................................... 89
IV.2.1 Geometric Optimization .............................................................................. 89
IV.2.2 Mulliken Atomic Charges Analysis ............................................................ 91
IV.2.3 Dipole Moments .......................................................................................... 95
IV.2.4 Frontier Molecular Orbital Analysis ............................................................ 95
IV.2.5 Global Reactivity Descriptors ..................................................................... 96
IV.2.6 Molecular Electrostatic Potential Surface (MESP) ..................................... 98
................... |
| Côte titre : |
Dch/0042 |
| En ligne : |
https://repository.univ-setif.dz/server/api/core/bitstreams/87d1073b-aa6b-459e-8 [...] |
| Format de la ressource électronique : |
pdf |
|
Ajouter le résultat dans votre panier Affiner la rechercheEtude théorique par la méthode DFT des composés α-aminophosphonates synthétisés à partir de para phénylenediamine / Anis Bouchama
“Synthesis, Biological Activities Evaluation, Density Functional Theory Investigation, and Molecular Docking studies of Hydroxybutyl and Hydroxypropyl Aminophosphonic Acids” / Anis Bouchama
