MoDRN:U Modules Introduction

Dr. Paul Anastas Welcome Video

 

Through a multidisciplinary collaboration between chemists, toxicologists, engineers and biologists from four different universities, MoDRN (Molecular Design Research Network) scientists aim to develop a systematic approach to understand and design chemicals that are both efficacious in their own right and chemically benign to the environment. The founding principle of MoDRN was derived from the 4th Principle of Green Chemistry, which states, “chemical products should be designed to preserve efficacy of function while minimizing toxicity”. With such strong collaborations with experts from different areas, it becomes possible to develop chemicals with the desired properties and predictable toxicity, and MoDRN serves as the important platform to achieve that goal.

The MoDRN team has developed a series of modules designed for undergraduate science and mixed-major/non-major classrooms to introduce concepts of green chemistry and sustainable chemical design. These are called the MoDRN:U Modules. The overall goal of these materials is to engage undergraduate students with educational concepts and activities that will aid dissemination of scientific principles relevant to the design of safer, next-generation molecules. Integrating MoDRN:U Modules into existing undergraduate lesson plans will allow students to make more connections with how interdisciplinary these topics truly are. The modules allow students to be introduced briefly to the relationship of physiochemical properties and toxicology, while providing faculty with resources for more information for their students. There are learning objectives for each module as well as a small assignment designed to be used in or out of class to assess comprehension (but not overwhelm time and syllabi schedules). The MoDRN:U Modules found by accessing the left menu are free to use and modify. Please return back frequently for new modules to come.

The MoDRN:U Modules were developed to introduce that concept that physicochemical properties and principles of toxicology are important aspects of consideration when designing safer chemicals. Undergraduate students will learn more about these topics by accessing each module and with small assignments associated with each module.

We value your feedback and will use it to help create more MoDRN:U Modules for use in your classroom. Please take a few minutes to fill out the evaluation form found at the end of each module. Or click here to access the evaluation through this homepage.

 

 

Physicochemical Property Modules

Chemical properties related to biological activity are receiving increased attention for designing out the inherent hazards of a chemical. Of the physicochemical properties, there are several that are especially important to estimating hazards and risks. They each have significant roles in exposure or hazard estimations. They are being explored in models and new tools for predicting the toxicity of chemicals. It is important to note that the importance of understanding the physiochemical properties of a chemical is due to the fact that these chemicals must interact with living systems in order to be considered toxic, and so recalling some basic physiology and biochemistry principles are important to putting together these chemical properties with why they impact living systems. 

Can chemical properties predict the inherent nature of the molecules and can they serve as a guideline to reduce hazard? To address this question, a group of researchers from Yale University performed an analysis to see if toxic compounds share similar physiochemical properties. They were motivated to explore if compounds with established toxicity would have similar property distribution. The study analyzed over 550 commercial chemicals classified as toxic by the EPA, including chemicals from various industry sectors including manufacturing, metal and coal mining, hazardous waste treatment, and electric utilities. After applying mathematical algorithms, the distribution of physiochemical properties of these toxic compounds was different than control group made of chemicals listed as benign by the EPA.  This study provides missing link that connects physiochemical properties with toxicity, and confirms that classification of highly toxic compounds is indeed possible by only couple of quantifiable parameters. This breakthrough became a stepping stone in the research which was proposed by Molecular Design Research Network (MoDRN) to develop property based toxicity prediction tools. Computational sciences can serve as a starting point, and rests on three pillars including chemical structure, dynamics, and reactivity for building predictive models.

Video: Dr. Jakub Kostal, Associate Research Scientist, The George Washington Unversity and CSO of Sustainability A to Z

If you are trying to make a decision without testing every possible endpoint and therefore without full knowledge, there are a variety of tools that you can use to fill data gaps. EPA has developed a number of “screening-level” tools that allow estimations in the absence of measured data. These tools generally use chemical structure and structure-activity relationships (SARs) to estimate the properties of the substance. These are not the only tools and, are not necessarily the best tools, but they are quite effective, they are free, and are certainly sufficient for beginning your process for designing safer chemicals. 

The following MoDRN:U Modules were developed that address Physicochemical Properties:  

  • Aqueous and Lipid Solubility
  • REDOX Reactions

Principles of Toxicology Modules

Toxicology is defined as investigation of any adverse effects that physical, chemical, or biological agents may have on living organisms and the environment. Toxicity can be acute or chronic; mild or severe. There are a myriad of interconnected issues that researchers and designers face when determining whether a chemical is toxic or not. Many have to do with the fate of the chemical and then how it impacts living systems and presents itself as toxic. If chemists can change any of the physiochemical properties of the chemicals they design, the chemical bioavailability can be tailored to the acceptable physiochemical level, where it can still carry out its functions while posing less threat to its biological host. When estimating potential toxicity of a chemical, toxicological concepts such as ADME (Absorption, Distribution, Metabolism and Excretion) and bioavailability should be considered, among many others. Physicochemical properties tie into these too as each chemical has a unique set of physical and chemical parameters which play an important role in the toxicity assessment. For example, a chemical can be characterized by its molecular weight, surface area, partition coefficient (LogP), and pKa. These parameters can evaluate if the compound is bioavailable (if it will absorb through the skin, lungs or GI tract) and how fast will it be metabolized and excreted. For a tutorial and background information about toxicology in general, please visit ToxLearn. ToxLearn is a joint project from the U.S. National Library of Medicine's Toxicology and Environmental Health Information Project (TEHIP) and the U.S. Society of Toxicology (SOT). Together, these agencies developed a two module learning tool, helping to highlight key toxicology features and background into further study in toxicology.

The following MoDRN:U Modules were developed that address Principles of Toxicology:

  • ADME and Toxicology
  • Oxidative Stress
  • Glutathione as a Tool for Testing Gene Function

Physicochemical Properties and Toxicology in Chemical Design Modules

Over 700 consumer products are introduced into the US market every year, but only approximately 85% of which are approved for manufacturing in spite of insufficient safety data. This is mainly due to the high cost associated with animal testing to generate toxicity data, and the necessity in developing a specialized set of protocol to evaluate the chemical comprehensively. As a result of this practice, consumers are left to bear the unknown, potentially harmful, factors from these new products until their hazards are realized. Sadly, many of these effects are not immediate, and thus the consequences are often unnoticed until a large quantity of the products have been released to the public and the environment. For this reason, there is an urgent need for a low-cost high throughput reliable screening approach to predict the toxicity of the chemicals during the early designing phase of the product – the in-silico approach.

With the rise in cost and increasing restrictions on animal testing in some countries, the in-silico approach make use of known chemical data to predict chemical properties and allow chemist to design a chemical that are much more likely to be toxic free for its purposes. Understanding parameters and how they influence ADME, for example, allow chemists to conduct the in-silico approach chemical design more efficiently. A chemist designing plasticizers for baby bottles may be able to prescreen candidate molecules and reject ones that are highly bioavailable.There are many chemical descriptors that can assist us in this work.  

Video: Dr. Adelina Voutchkova-Kostal, Assistant Professor of Chemistry, The George Washington University

The following MoDRN:U Modules were developed that address physicochemical properties and toxicology in chemical design:

  • Crossroads of Computational Chemistry and Toxicology
  • Using ProTox
  • ADME and Rational Chemical Design

We value your feedback and will use it to help create more MoDRN:U Modules for use in your classroom. Please take a few minutes to fill out the evaluation form found at the end of each module. Or click here to access the evaluation through this homepage.

This material is based upon work supported by the NSF Division of Chemistry and the Environmental Protection Agency under Grant No. 1339637.