One of the fundamental principles of green chemistry is to design chemical products that minimize adverse consequences to human health and the environment. While chemists have been designing molecules for 200 years to have a limitless range of commercial applications, little or no attention has been given to developing commercial chemicals while avoiding hazards and toxicity. This book is the first to provide chemists with useful, practical guidance on how to minimize or avoid a wide range of hazards. Building on the insights gained from the pharmaceutical industry over the past 25 years on how to create desirable biological effects, the authors demonstrate how to avoid undesirable biological effects by design.
Author(s): Predrag V. Petrović, Paul T. Anastas
Publisher: Jenny Stanford Publishing
Year: 2023
Language: English
Pages: 261
City: Singapore
Cover
Half Title
Title Page
Copyright Page
Dedication
Table of Contents
Preface
Acknowledgments
Introduction
Chapter 1: Hazard
1.1: What Is a Chemical Hazard?
1.2: What Is a Toxicological Hazard?
1.3: What Is an Ecotoxicological Hazard?
1.4: What Is a Physical Hazard?
1.5: What Causes Explosivity?
1.6: What Is “Oxygen Balance” and How Does It Calculate Explosivity?
1.7: What Is a Global Hazard?
Chapter 2: ADME
2.1: Why Is Absorption Crucial to Toxicity?
2.2: What Is Lipinski’s Rule of Five?
2.3: What Is Log P/Log Kow?
2.4: How Does Log P Affect Absorption?
2.5: What Is the Difference Between Active and Passive Transport?
2.6: Why Is Metabolism Crucial to Toxicity?
2.7: What Is the Bioactivation Step in Metabolism?
2.8: What Is the Detoxification Step in Metabolism?
2.9: What Is Distribution and Why Is It Crucial to Toxicity?
2.10: What Properties Promote Distribution?
2.11: What Is Excretion and Why Is It Crucial to Toxicity?
Chapter 3: Degradability
3.1: What Is the Difference Between Degradability and Biodegradability?
3.2: What Is Photolytic Degradation?
3.3: What Is Hydrolytic Degradation?
3.4: What Are Thermolytic Degradation and Pyrolysis?
3.5: How Is Biodegradability Measured?
3.6: What Is Aerobic Degradation?
3.7: What Is Anaerobic Degradation?
3.8: How Does Branching of a Carbon Chain Impact Biodegradation?
3.9: How Do Fused Rings Impact Biodegradation?
3.10: How Do Heteroatoms Impact Biodegradation?
3.11: How Do Charged Functional Groups Impact Biodegradation?
3.12: What Is Persistence?
3.13: Why Are Perfluorinated Compounds so Persistent?
Chapter 4: Dose/Response/Risk
4.1: What Is a Dose?
4.2: What Is Dose-Response?
4.3: What Can Dose-Response Curves Tell Us?
4.4: What Is Toxic Dose Versus Effective Dose?
4.5: What Are the Pathways of Exposure?
Chapter 5: Pharmacodynamics
5.1: What Is Pharmacodynamics?
5.2: What Are Receptor Interactions?
5.3: What Does the HOMO–LUMO Gap Has to Do with Pharmacodynamics?
Chapter 6: Classes of Chemicals
6.1: What Are the Biggest Concerns About Organohalogens?
6.2: What Are the Biggest Concerns for Epoxides?
6.3: What Are the Biggest Concerns for Polymers?
6.4: What Are the Biggest Concerns with Nitriles?
6.5: What Are the Biggest Concerns with Electrophiles?
6.6: What Are the Biggest Concerns with Asbestos?
Chapter 7: Design Rules for Safer Chemicals
7.1: Strategies to Minimize Hazard
7.2: How to Design to Reduce Toxicity?
7.3: How to Design for Minimized Ignition?
7.4: How to Design to Minimize Explosivity?
7.5: How to Design to Reduce Absorption?
7.6: How Can We Change Properties/Structure to Minimize Inhalation?
7.7: How Can We Change Properties/Structure to Minimize Transport Across the Gastrointestinal Tract?
7.8: How Can We Change Properties/Structure to Minimize Transport Across Skin?
7.9: How to Design to Modify Active and Passive Transport?
7.10: How to Design to Reduce Persistence?
7.10.1: Biodegradation
7.10.2: Photolytic Degradation
7.10.3: Hydrolytic Degradation
7.10.4: Thermal Degradation
7.11: How to Design to Minimize Bioaccumulation/Bioconcentration?
7.12: What Structural Features Can Be Built in to Avoid Bioactivation?
7.13: What Structural Features Can Be Built in to Promote Detoxification?
7.14: What Properties Promote Distribution?
7.15: How to Design to Promote Excretion?
7.16: What Structure/Property Changes Can BeMade to Disfavor Toxic Mechanisms of Action?
7.17: How to Design to Reduce Carcinogenicity andMutagenicity?
7.18: Specific Classes of Chemicals and Design Suggestions: Electrophiles
7.18.1: Aromatic Amines and Azo Dyes
7.18.2: Aldehydes and Substituted Aldehydes
7.18.3: Acylating Agents and Isocyanates
7.18.4: Alkyl Esters of Strong Acids
7.18.5: Aliphatic Azo, Azoxy, and Hydrazo Compounds
7.18.6: Carbamates
7.18.7: Epoxides and Ethylenimines
7.18.8: Lactones
7.18.9: Haloalkanes and Substituted Haloalkanes
7.18.10: Michael Addition Acceptors
7.18.11: N-nitrosamines
7.18.12: Organic Peroxides
7.18.13: Organophosphorus Compounds
7.18.14: Polycyclic Aromatic Hydrocarbons
7.18.15: Per- and Polyfluoroalkyl Substances
7.18.16: Quinones and Quinone-like Compounds
Chapter 8: Case Studies
Chapter 9: The Path Forward
Index
