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Announcing the winner of the 2022 ACS Central Science Disruptors and Innovators Prize

Photo courtesy of Gabriella Bocchetti

The American Chemical Society (ACS) Publications Division and ACS Central Science are proud to announce the winner of the ACS Central Science Disruptors & Innovators Prize, Clare Grey, D.Phil., FRS, of Cambridge University. Since 2019, the ACS Central Science Disruptors & Innovators Prize has recognized individuals who, through their innovative research, are advancing the central science of chemistry.

Professor Grey is awarded the Prize for her extensive and disruptive research in pioneering applications of solid state nuclear magnetic resonance to materials of relevance to energy and the environment.

“I’m honored and excited to have won this award – a wonderful recognition of not just me, but also the students and post-docs who have worked with me in both the US and the UK to make this happen,” says Grey. “It is also great to see my fundamental science being appreciated in this way.” 

Prof. Grey is the Geoffrey Moorhouse-Gibson professor of chemistry at Cambridge University and a fellow of Pembroke College Cambridge and holds a Royal Society professorship. She received a BA and D.Phil. in chemistry from Oxford University. She was the founding director of the Northeastern Chemical Energy Storage Center, a US Department of Energy, Energy Frontier Research Center, a Center she started while a Professor at Stony Brook University. She is currently the director of the EPSRC Centre for Advanced Materials for Integrated Energy Systems and an Expert Panel member of the Faraday Institution. Grey is the recipient of numerous awards and honors, including the Richard R. Ernst Prize in Magnetic Resonance, the Royal Society Hughes Award, and the Körber Award for her contributions to the optimization of batteries using NMR spectroscopy, and she is a foreign member of the American Academy of Arts and Sciences. Her current research interests include the use of solid-state NMR and diffraction-based methods to determine structure-function relationships in materials for energy storage (batteries and supercapacitors) and conversion (fuel cells). She is a cofounder of the company Nyobolt, which seeks to develop batteries for fast charge applications. 

Disruptors and Innovators Prize 2022

“It is my tremendous honor to present the 2022 ACS Central Science Disruptors & Innovators Award to Prof. Clare Grey, in recognition of her pioneering work in fundamental studies of rechargeable battery materials using solid state NMR methodology,” says Carolyn Bertozzi, Ph.D., Editor-in-Chief of ACS Central Science. “Prof. Grey is an inspiration to the scientific community and her work perfectly embodies the power of chemistry as the central science.”

Prof. Grey will accept the prize at an upcoming virtual symposium, during which she will present a Disruptors Lecture. More details can be found on the ACS Central Science Disruptors & Innovators Prize website.

Visit the site now

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Selected publications

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Single-Source Deposition of Mixed-Metal Oxide Films Containing Zirconium and 3d Transition Metals for (Photo)electrocatalytic Water Oxidation

Victor Riesgo-Gonzalez, Subhajit Bhattacharjee, Xinsheng Dong, David S. Hall, Virgil Andrei, Andrew D. Bond, Clare P. Grey, Erwin Reisner, and Dominic S. Wright

 

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Electrolyte Reactivity at the Charged Ni-Rich Cathode Interface and Degradation in Li-Ion Batteries

Wesley M. Dose, Israel Temprano, Jennifer P. Allen, Erik Björklund, Christopher A. O’Keefe, Weiqun Li, B. Layla Mehdi, Robert S. Weatherup, Michael F. L. De Volder, and Clare P. Grey

 

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Cycle-Induced Interfacial Degradation and Transition-Metal Cross-Over in LiNi0.8Mn0.1Co0.1O2–Graphite Cells

Erik Björklund, Chao Xu, Wesley M. Dose, Christopher G. Sole, Pardeep K. Thakur, Tien-Lin Lee, Michael F. L. De Volder, Clare P. Grey, and Robert S. Weatherup

 

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New Magnetic Resonance and Computational Methods to Study Crossover Reactions in Li-Air and Redox Flow Batteries Using TEMPO

Evelyna Wang, Evan Wenbo Zhao, and Clare P. Grey

 

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Exploring the Role of Cluster Formation in UiO Family Hf Metal–Organic Frameworks with in Situ X-ray Pair Distribution Function Analysis

Francesca C. N. Firth, Michael W. Gaultois, Yue Wu, Joshua M. Stratford, Dean S. Keeble, Clare P. Grey, and Matthew J. Cliffe

 

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Improved Description of Organic Matter in Shales by Enhanced Solid Fraction Detection with Low-Field 1H NMR Relaxometry

Panattoni, A. A. Colbourne, E. J. Fordham, J. Mitchell, C. P. Grey, and P. C. M. M. Magusin

 

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Density Functional Theory-Based Bond Pathway Decompositions of Hyperfine Shifts: Equipping Solid-State NMR to Characterize Atomic Environments in Paramagnetic Materials

Derek S. Middlemiss, Andrew J. Ilott, Raphaële J. Clément, Fiona C. Strobridge, and Clare P. Grey

Get to Know ES&T Award Winner Menachem Elimelech

Professor Menachem Elimelech was recently named one of the winners of the Outstanding Achievements in Environmental Science & Technology Award from Environmental Science & Technology. Professor Elimelech is the Sterling Professor of Chemical and Environmental Engineering at Yale University, where his research focuses on membrane-based processes for energy-efficient desalination and wastewater reuse. He also researches sustainable production of water and energy generation with engineered osmosis, environmental applications and implications of nanomaterials, and water and sanitation in developing countries.

Read on to learn more about Professor Elimelech and his work.

What does this award mean to you?

I am grateful that ACS and the editors have recognized the importance of our work on membrane-based technologies for desalination, water reuse, and brine management. Credit goes to my current and former graduate students and postdocs for their contributions.

What have been some of the key influences that have shaped how your career has developed?

The realization about two decades ago that water scarcity is a serious global problem and that climate change exacerbates water scarcity has inspired me to work on membrane technologies as a means to augment water supply by utilizing non-conventional water sources such as seawater and wastewaters. I believe that seawater and brackish water desalination and wastewater reuse, when used appropriately, can be sustainable methods for augmenting water supply in water-scarce regions.

What do you consider some of the most important highlights from your career so far?

This is a tough question to answer. I am proud of the many graduate students and postdocs that I mentored who are now quite successful in their careers. I am also proud of the environmental engineering program at Yale University, which I founded over two decades ago. The program has graduated outstanding individuals who are working relentlessly to solve our environmental challenges. I am also happy that our papers help to set the research agenda in membrane-based desalination and water purification and steered the membrane community to relevant research topics that have a direct impact on industry and humanity.

Describe your current area of research (or areas of interest).

My current research is in the general area of membrane-based technologies at the water-energy nexus. Specifically, we are working on membrane-based processes for energy-efficient desalination and wastewater reuse, advanced materials for next-generation environmental separation and water decontamination technologies, and fundamental mechanisms of selective ion separations in membrane systems. In recent years, we have also worked on the development of technologies for the management of brines from inland desalination plants and industrial wastewaters, such as those produced in the oil and gas industry. Specifically, we proposed the use of ultrahigh-pressure reverse osmosis (UHPRO) as a technology to displace energy-intensive thermal evaporators that are commonly used for brine management. More recently, we have developed a new membrane-based technology for concentrating brines, referred to as low salt rejection reverse osmosis (LSRRO).

What motivates you to be a researcher in this field of environmental science & technology?

I always wanted to work on topics related to water, maybe because I grew up in southern Israel, a semi-arid region that receives less than five inches of rain annually. Water is our most precious resource, and I am excited to work on technologies to ensure adequate and safe water globally.

What are the major challenges in this area, and what type of work can we look forward to seeing from you in the future?

Considering the accelerated adverse impacts of climate change on water resources, one of the major challenges will be to augment freshwater supply using unconventional water sources. Industrial wastewaters represent a major source of unconventional water that can be reused to extract fresh water and minimize discharge to the environment. For the reuse of industrial wastewaters, there is a need to develop energy-efficient membrane-based technologies that can achieve high water recovery and produce fresh water at a low cost. There is also a need to investigate the potential of resource recovery from the concentrated brines generated during the reuse of these industrial wastewaters.

What is your advice for young investigators?

I would encourage young researchers to find the right balance to work on fundamental research but also on relevant research that may help humanity. This may be challenging because our university tenure system and prestigious journals are biased toward “hot” topics rather than applied and relevant research. I also encourage young investigators to focus their research on one or two thrusts initially and make an impact before expanding their research later in their careers. Lastly, researchers should enjoy their research and mentoring and inspire their students to be inquisitive and happy in what they are doing. A happy and inspiring work environment will lead to creative research.

Announcing the 2022 Outstanding Achievements in Environmental Science & Technology Award Winners: The Americas Region

The Outstanding Achievements in Environmental Science & Technology Award recognizes change makers, whose research and service contributions to the fields have substantially supported improvements in human health and/or the environment.

Please join Environmental Science & Technology in warmly congratulating winners of the 2022 award: Professor Jerald L. Schnoor, Allen S. Henry Chair in Engineering, University of Iowa, and Professor Menachem Elimelech, Sterling Professor Chemical and Environmental Engineering, Yale University.

Professor Jerald L. Schnoor was recognized for his pioneering research on phytoremediation as a sustainable remediation technology, discovering novel pathways for the uptake, sequestration, and degradation of organic chemicals in the environment, and for his fundamental contributions, leadership, and service in water quality engineering science, in modeling, chemistry, molecular biology, and policy. Explore his research published in ACS journals here.

Professor Menachem Elimelech was recognized for his vision, influence, leadership, and major impacts and technological innovations on the field of water quality engineering and treatment working toward clean water for global health and sustainable development in the face of global water scarcity. Explore his research published in ACS journals and read an interview about his life and work.

Open Call for Nominations: 2022 Industrial & Engineering Chemistry Research Influential Researcher Awards – Europe, Africa, Middle East

For five years Industrial & Engineering Chemistry Research has been recognizing and publishing the contributions of early-career investigators from around the world through its annual Class of Influential Researchers. In 2022, these awards will focus on researchers in the regions of Europe, the Middle East, and Africa, with future years focusing on other parts of the world. We invite nominations (including self-nominations) of researchers in Europe, Africa, the Middle East within the first ten (10) years of their independent career, who are doing exceptional research within chemical engineering and applied chemistry.

Nomination Deadline: February 1, 2022

Eligibility:

  • Researchers based at affiliated institutions located in Europe, the Middle East, or Africa and within the first ten (10) years of their independent career (2012-, independence defined as after postdoc appointments or last educational training)
  • This award must be based on research done during the nominee’s independent career, and cannot be based on research completed as part of their graduate education or post-doctoral training.
  • Nominees must not have been recognized in previous Classes of Influential Researchers (2021, 202020192018, 2017)
  • We encourage nominations of researchers from government, industrial, and university labs.

Required:

  • Completed nomination form detailing name, position, institution, country, preferred topical section, year candidate’s independent career began, etc.
  • A brief statement (3,500 characters or about 500 words maximum) describing research contributions made during the nominee’s independent career
  • List of up to 5 contributions to research (publications, patents, reports, etc.) during their independent career, each with a 50-word maximum description of significance or impact. (Do not upload the actual articles – just the 50-word statements)
  • Website URL to professional website, CV, Google Scholar profile, or LinkedIn (Note: If no link available, insert “n/a” and email a short CV – two pages maximum – to eic@iecr.acs.org)

Apply By Filling Out the Form Below or By Clicking Here

Additional Information:

We anticipate selecting up to five (5) award recipients within each of the eight (8) topical sections covered by I&EC Research. These areas are:

  • Applied Chemistry
  • Bioengineering (broadly defined)
  • Kinetics, Catalysis, and Reaction Engineering
  • Materials and Interfaces
  • Process Systems Engineering
  • Separations
  • Thermodynamics, Transport, and Fluid Mechanics
  • General Research

Each 2022 winner will be invited to submit an article to I&EC Research by June 1, 2022, along with their photograph and bio sketch. If their article is accepted, each winner will receive an award plaque and be publicized by ACS Publications as a member of the 2022 Class of Influential Researchers. These articles will be collected in a virtual special issue of I&EC Research highlighting the researchers and their work.

The selection committee will include I&EC Research editors and editorial advisory board members.

2022 James J. Morgan Environmental Science & Technology Early Career Award Winners Announced

The James J. Morgan Environmental Science & Technology Early Career Award, named after the first Editor-in-Chief of Environmental Science & Technology, recognizes those early career researchers who are standing on our shoulders. These are the researchers who are seeing the farthest horizons and leading the fields in new directions through creative, new ideas consistent with Morgan’s early contributions to environmental chemistry.

This year, we received a significant number of nominations for the James J. Morgan Early Career Award from Europe, the Middle East and Africa. Please join us in congratulating the 2022 James J. Morgan Early Career Award winners:

  • Gang Liu, University of Southern Denmark, Denmark
  • Denise M. Mitrano, ETH Zürich, Switzerland
  • Peng Zhang, University of Birmingham, U.K.
  • Matthieu Riva, I’IRCELYON, France

Learn more about the winners, and what this means to them below.

Professor Gang Liu, University of Southern Denmark, Denmark

Tell us about yourself.

I am a Professor of Industrial Ecology at the University of Southern Denmark. I am Chinese but have been living and working in the Nordic circle since 2008, first in Norway and then in Denmark. With this background and combining the significant environmental challenges in China and the sustainability-oriented mindset embedded in the Scandinavian culture, research, and education, it is a dream job to be a professor on environmental sustainability at a research university.

What does this award mean to you?

It is my great honor to receive this James J. Morgan Early Career Award. It means a lot to me to be acknowledged by the most reputed journal in our field. I can still remember the cheerful moments during my Ph.D. when my work got published in Environmental Science & Technology and later awarded runner-up Best Paper. In the past years, my research group has always put it as our primary target journal. Furthermore, I feel particularly grateful to receive this award named after James J. Morgan, who is the founding Editor-in-Chief of this journal and a great scientist who had inspired so many researchers (including me) to be creative and try new pathways. Last but not least, this award gives me an opportunity to acknowledge my mentors, colleagues, and students who have helped me along the way.

What are you working on now?

My main field is industry ecology, which is an emerging multidisciplinary field that studies materials and energy stocks and flows through industrial systems and is often recognized as the science for circular economy and sustainability. In short, I have been developing and applying different systems approaches for addressing complex environmental problems such as climate change, resource and waste management, and urban sustainability and informing the societal circular, low carbon, and just transition. Empirical case studies in recent years include sustainable metal cycles, agrifood chains, urban systems, and low-carbon technologies.

What advances are you hoping to see in your field in the next decade?

There are many technological advances that I hope to see in my field in the next decade, including further methodology integration from various disciplines and more automated data generation (e.g., using big data) and analysis facing urgent and increasing sustainability challenges. However, most often, we already have the technologies, solutions, and understanding on addressing these challenges, be it climate or resource-related. Therefore, I would particularly like to see how such knowledge can be implemented in the real world and used to inform governmental and industry policy and actions in the next years.

Can you share some advice for other young investigators?

As young investigators, you should always aim high and dream big. You may sometimes feel lonely when walking on the forest trails (than on the crowded highways), but as James J. Morgan demonstrated, new pathways and ideas can lead to new directions that are necessary for addressing our complex environmental problems. As our global challenges get increasingly intertwined, I think systemic and multidisciplinary efforts are also increasingly needed. So be prepared to get out of the box and be open to theories, methods, and data from other disciplines for common sustainability purposes.

Where do you hope to see your career 10 years from now?

2030 is a year that many of our resource, climate, and sustainability-related targets are benchmarked, including the United Nations’ 2030 Sustainable Development Goals. So, I hope in 10 years, together with other researchers working on sustainable systems, we can say our research has made an impact in this successful journey.

View articles published by Professor Gang Liu.

Professor Denise M. Mitrano, ETH Zurich, Switzerland

Tell us about yourself.

As an environmental analytical chemist, my research focuses on the distribution and impacts of anthropogenic materials in technical and environmental systems. I am particularly interested in developing analytical tools to systematically understand the mechanisms and processes driving the fate, transport, and biological interactions of particles, such as engineered nanomaterials and nano- and microplastics. In this context, my research group uses these results to assess the risks of anthropogenic materials across various ecosystems and scales. I have an interest in a “safer by design” approach for both nanomaterials and plastics, which is exemplified by working on the boundaries of environmental science, materials science, and policy to promote sustainability and environmental health and safety of new materials.

The thing I like most about being an analytical chemist is that other researchers are able to use our methods and take them even further to better investigate their own research objectives. In a way, this amplifies my contributions across the field of environmental sciences to provide others with the tools to answer their most interesting questions, in addition to carrying out our own research objectives. Being an expert in nanometrology has allowed me to collaborate across many different research fields with colleagues whose expertise is very different than mine, and so I’m constantly able to learn about new areas of science.

What does this award mean to you?

It is both exciting and humbling for my work to be recognized by receiving this years’ James J. Morgan Early Career Award and to have my name be listed amongst the other excellent up-and-coming researchers in the field of environmental sciences. I am very passionate about the work that we do in my lab but also inspired by the amazing students who work alongside me and thankful for my mentors and colleagues who have helped shape my career and outlook to date.

What are you working on now?

I have been very interested in applying the skills and process understanding I gained in studying engineered nanomaterials to different particulate materials of emerging concern, including plastics.  However, analytically, measuring plastics can be very different and more challenging than inorganic (nano)particles. Therefore, I developed a new approach to synthesize nano- and microplastics doped with a trace metal to more easily and quickly quantify them in complex matrices using techniques that are more standardized for metals analysis, including ICP-MS and single-particle ICP-MS.  By using the metal as a proxy for the plastics, we can spike them into a variety of laboratory and pilot-scale facilities, which has allowed us to investigate the fate and transport of plastics in environmental systems (waterways, porous media), wastewater, and drinking water treatment plants and to study biological uptake and interactions of nano- and microplastics. This approach has opened up a completely new avenue for those studying plastic pollution and has provided many new opportunities for collaboration with other research groups.

Can you share some advice for other young investigators?

Be brave and think outside the box! As a young scientist, you have the opportunity to focus on a new field and develop innovative methods that are not yet established. This may entail risks, but in the best-case scenario, you can become a pioneer in your own field.

Perhaps the two things which have helped my professional success the most are to keep an open mind and to ask many questions. This has opened the door for a lot of new ideas and collaborations which wouldn’t have come about if I were solely focused on my day-to-day work. Naturally, learning to balance the demands of organizing multiple projects on different topical subjects simultaneously took time, but in the end, I feel that I am gaining an increasingly holistic view of my field, which helps me to better identify key research gaps and develop better research objectives.

Where do you hope to see your career 10 years from now?

On a day-to-day basis, to me, science, especially analytical method development, is about problem-solving and the excitement when you have finally accomplished a difficult puzzle (sometimes after much trial and error!). But the implications of our work go beyond the laboratory. The natural environment is experiencing ever-increasing pressures from anthropogenic stressors. Understanding how human activities influence physical, chemical, and biological cycles is a central component of modern geosciences, and I find it very rewarding to contribute knowledge that can lead towards the protection of our waterways and soils. In the future, I hope to continue to bridge academic science with other stakeholders from policy, industry, and the public to make scientifically informed decisions about the materials we use and how this impacts the natural environment.

View articles published by Professor Denise M. Mitrano.

Dr. Matthieu Riva, Institut de Recherches sur la Catalyse et l'Environnement de Lyon (I'IRCELYON), France

Dr. Matthieu Riva received his doctoral degree from the University of Bordeaux in 2013. He obtained a postdoctoral fellowship from the Camille and Henry Dreyfus Foundation to work with Professor Jason Surratt at the University of North Carolina at Chapel Hill.  In 2016, he joined Professor Mikael Ehn’s group at the University of Helsinki, Finland. After these postdoctoral research positions, in 2018, he joined the Centre National de la Recherche Scientifique (CNRS) as a senior researcher at the Institute of Research on Catalysis and Environment at Lyon, France. His research interests include the chemical characterization of organic aerosol particles and low volatile material using advanced mass spectrometric techniques.

What does this award mean to you?

The James J. Morgan Environmental Science & Technology Early Career Award aims to recognize the early career researchers who are initiating and creating new ideas consistent with Morgan’s contributions in environmental chemistry. As a result, I am greatly honored to be awarded the James J. Morgan Early Career Award and to be associated with such an outstanding pioneer who inspired and inspires many (young) scientists. This award is also the recognition of the support and research excellence of my mentors, students, postdoctoral researchers, collaborators, and colleagues. So, I would like to thank all of them for inspiring me.

What are you working on now?

I am currently pursuing the analytical developments initiated in the last two years and using this newly developed technology to better characterize the chemical processes governing the formation and growth of newly formed particles.

What advances are you hoping to see in your field in the next decade?

The main advances that I would hope in my chosen research area would be to direct research efforts toward studying the impacts of Global Warming on the global ecosystem in link with atmospheric chemistry. For example, upon environmental stress or the development of pathogen/parasite-induced diseases, living ecosystems emit a wide variety of molecules as a defense mechanism or for signaling. As a result, the emission profile of volatile organic compounds of an impacted ecosystem can greatly change and will ultimately influence ozone levels and particle formation on both regional and global scales.

Can you share some advice for other young investigators?

I think curiosity and persistence are fundamental aspects of research. Being able to conduct research with passion while pursuing and trying to involve something different in the research would make the research experience more interesting. I would emphasize to the researchers that pursuing new ideas or concepts is always associated with the risk of failure, but from every experience, we learn something.

View articles published by Dr. Matthieu Riva.

Dr. Peng Zhang, University of Birmingham, U.K.

Dr. Zhang obtained his Ph.D. in Bioinorganic Chemistry from the University of Chinese Academy of Sciences in 2013. He joined the University of Birmingham as a senior research fellow in 2018, following his position as an associate professor at the Institute of High Energy Physics (CAS) since 2015. His research interests span nanosafety, environmental toxicology, nanomaterials application in agriculture, and environmental remediation.

His specific research areas include:

  • developing advanced techniques (e.g., stable and radioactive isotope labeling, chemical labeling, etc.) to enhance the sensitivity for tracing the fate of nanomaterials in the environment and biota.
  • study transport and fate of nanomaterials in the human body and the link with their human safety.
  • explore nano-enabled technology to improve plant growth, increase use efficiency of agrochemicals, and reduce agriculture derived environmental pollution.

He is considered a leading researcher with a broad vision and innovative ideas in developing solutions for sustainable nanotechnology and nano-enabled agriculture.

Tell us about yourself.

I am fascinated by science and like to stay in the lab. Outside of the lab, I like basketball, movies, travel, and playing with my little daughter.

What does this award mean to you?

It’s a great honor to be selected as a recipient of the James J. Morgan Early Career Award. The award recognizes me as part of the wonderful and creative scientific community. It is a big motivation for me to keep going on the path of science.

What are you working on now?

The central objective of my research is to find sustainable solutions for the environment. A key focus is to find nanotechnology-based solutions to enable sustainable agriculture. The global agriculture and food security sector is facing a wide range of challenges, such as low crop yields, declining soil health and fertility, shrinking arable land, and low use efficiency of agrochemicals, mainly due to excessive use of fertilizers and pesticides. Using nanotechnology, we may increase the crop yield whilst reducing the agriculture-derived environmental contaminations, and we will have more chances to win the battle against food security.

Another work I am doing now is nanosafety, a continuation of my past research. Ensuring the safety of nanotechnology is an important prerequisite for its application in other areas, including agriculture. Specifically, we are evaluating the behavior and toxicology using a variety of models such as cell lines, higher plants, and animals such as Daphnia mangaand earthworm.

What advances are you hoping to see in your field in the next decade?

The ultimate goal of our research is to ensure the sustainability of society. What my research can contribute is to help to achieve one of the UN 17 sustainable development goals (SDGs), i.e., zero hunger. More specifically, the goal is to end hunger, achieve food security and improve nutrition and promote sustainable agriculture. In the next decade, I hope to see more advances in this field to ensure we achieve this goal as time won’t wait for us. I believe more nano-enabled sustainable solutions can be developed, but I hope more of these solutions can be tested in the real world and put into realistic applications.

Can you share some advice for other young investigators?

Keep positive and patient. Failure is common on the path of science. The best solution is to keep a positive mindset and be patiently waiting and finding solutions. Time management is also important, so make sure you find a good time system to balance work and family.

View articles published by Dr. Peng Zhang.

2021 ICBS Young Chemical Biologist Award Winners Announced

ACS Chemical BiologyACS Pharmacology & Translational ScienceACS Omega, and Biochemistry are proud to continue supporting the ICBS Young Chemical Biologist Award.

This award is dedicated to advancing the career development of young chemical biologists. The individuals who receive this honor are recognized annually for their impactful work within the global community.

Learn more about the 2021 ICBS Young Chemical Biologist Award Winners:

Leslie Aldrich, University of Illinois Chicago

What does winning this year’s award mean to you?

Receiving this award is such an honor! This award provides recognition for the tenacity and creativity of my group and gives me the opportunity to highlight our recent discoveries and future directions. I hope that my lecture will inspire others to dream big and to get excited about how chemical biology can impact human health.

What exciting projects are you currently working on?

A major focus of our research group is developing new small-molecule probes for challenging targets to facilitate drug discovery efforts for unmet medical needs. We are particularly interested in autophagy, a catabolic process that maintains cellular homeostasis. We are currently targeting protein-protein interactions that are important for autophagy initiation to develop inhibitors with improved selectivity that could lead to new therapeutic strategies for cancer. Autophagy can enable cancer cells to overcome stress, including hypoxia, nutrient deprivation, and chemotherapy-induced stress, to survive and progress to advanced malignancy. By selectively inhibiting autophagy in cancer patients, we could restore cancer cell sensitivity to chemotherapy and minimize off-target effects. In addition to inhibiting early-stage autophagy, we are also developing probes that modulate autophagy through different mechanisms to evaluate their effects in neurodegenerative diseases. It is possible that molecules that induce autophagic flux could restore homeostasis in these diseases and prevent neuronal cell death. Precise control of the autophagy pathway could lead to numerous applications and benefits!

What do you think is the biggest challenge currently in your area of research?

Autophagy is a challenging pathway to study due to its dual nature in disease: prevention of cell death may be beneficial in neurodegeneration but is detrimental in cancer. Also, many different targets can activate or inhibit autophagy, and identifying which targets are the most promising for therapeutic modulation can be challenging. This will require careful mechanistic assessment and in vivo evaluation of new probes to discover which mechanisms of modulation are most beneficial. Furthermore, targeting protein-protein interactions has historically been considered difficult for drug discovery and development. Recent successes, like Venetoclax, have highlighted the exciting potential of this strategy for the development of novel, selective therapies.

What would your advice be to someone just starting out in the field?

I have two pieces of general advice for starting a chemistry faculty position.

  1. Establish a supportive environment that prioritizes mental and physical health in your own life and in the lives of your trainees. This is critical for productivity, success, and happiness. I personally like to spend time running and thinking of new ideas or solutions to problems, and then I’m excited to get back to my computer and lab to further develop a hypothesis and to make plans for the critical experiments to test it.
  2. Seek out supportive mentors. It can be overwhelming setting up a new lab, teaching new classes, and training new graduate students, so it’s especially important to have a network of people who can give insightful advice and provide encouragement.

This is my advice for starting out in the chemical biology field.

  1. Take risks! Chemical Biology is highly interdisciplinary, and there are many challenging problems. There is an inherent risk to tackling any challenging problem, but as a chemical biologist, you have a diverse skillset that lends itself to devising creative solutions.
  2. Collaborate! Working with talented, supportive collaborators to design experiments, analyze results, and discuss future directions can really advance your research and lead to new discoveries and ideas due to diverse experiences and viewpoints.

What advances do you hope to see in your field over the next decade?

I hope to continue seeing advances in the determination of mechanisms of small-molecule probes discovered through phenotypic screening and the evaluation of selectivity of probes for non-traditional targets. I also hope to see new and exciting approaches to developing small-molecule tools to modulate complex cellular pathways, and I look forward to the new knowledge we will gain from analyzing the results of selective pathway modulation in basic biology and human disease. Finally, I hope to see a continual push for improving diversity, equity, and inclusion in our field, because all people and voices are needed to realize the discoveries of the future.

Read Leslie Aldrich’s contributions to the field through their ACS published research.

Jeremy Baskin, Cornell University

What does winning this year’s award mean to you?

Above all, this award is a recognition of the contributions of a creative and dedicated team of students and postdoctoral scholars working in my lab, and I am so grateful for their innovative ideas, their passion for research, and for pushing me to become a better scientist and mentor. Additionally, this award is a recognition that lipids and membranes are currently, and will hopefully remain for many years, a fertile area for investigation at the chemistry–biology interface.

What exciting projects are you currently working on?

We are excited to apply our tools to frontier questions in lipid biology. Two examples: How do cells maintain the non-equilibrium localization of lipids in specific membranes? We are working on projects to define the rules of lipid transport between organelles and across bilayers. How do cells regulate the production and consumption of bioactive signaling lipids? Their chemical structures and the enzymes that produce them have mostly been identified, but the factors that regulate their activity are not well understood in many instances, and we are combining our labeling tools with CRISPR screening to discover new regulatory networks.

What do you think is the biggest challenge currently in your area of research?

Unlike proteins, lipids are not directly genetically encoded but are instead the products of a complex and interconnected metabolic network. Much of the challenge of studying lipids and membranes stems from this metabolic complexity and therefore motivates the development of precision tools for visualization and manipulation of lipid production and metabolic flux.

What would your advice be to someone just starting out in the field?

I would advise newcomers to identify a niche where there are important questions. The questions don’t have to be new, but one should strive to bring something new to address the questions in a different way. Even for tool-builders, being question-focused can increase the impact of your advances. The other piece of advice is to pick one’s mentors carefully and surround oneself with a good support system of mentors and collaborators.

What advances do you hope to see in your field over the next decade?

Broadly, I hope to see more complete molecular descriptions of the fascinating and complicated phenomena of lipid transport and homeostasis. I would love to increase connections at the chemistry–biology interface, which is a two-way street: more biologists adopting chemical tools and adopting a chemically oriented mindset, and more chemists gaining a deeper appreciation of the complexity of cellular systems and pushing methods advances toward important applications in biology.

Read Jeremy Baskin’s contributions to the field through their ACS published research.

Nir London, Weizmann Institute of Science

What does winning this year’s award mean to you?

I’m deeply honored and proud to receive this award. As someone who started his career strictly as a computational scientist and have only transitioned into experimental chemical biology as I started my independent career here at the Weizmann Institute, this recognition means a lot to me. The chemical biology community is awesome, friendly and collegial and I’m very happy to be accepted into the fold.

What exciting projects are you currently working on?

A big part of our lab is focused now on our recently published “CoLDR”(covalent ligand directed release) chemistry. This technology allows to both functionalize targeted covalent inhibitors, as well as to site-specifically label target proteins in live cells. We are now developing new applications for this chemistry in the domains of targeted protein degradation and protein proximity inducers in general.

Another project that we are still very much involved with is the COVID moonshot – an ambitious open-science initiative I co-founded with several like-minded scientists early in 2020. We aim to develop a safe and cheap therapeutic against SARS-CoV-2 (targeting the Main Protease) through a combination of crowdsourcing and structure based-design. Recently we were awarded a grant by the Wellcome Trust that should enable us to advance compounds to pre-clinical testing and hopefully to IND.

What do you think is the biggest challenge currently in your area of research?

I think one of the biggest challenges in the field of covalent inhibitors, which is heavily studied nowadays, is the discovery of new covalent ‘warheads’ against amino acids other than Cysteine, that are both sufficiently selective and stable, as well as suitable for in vivo administration.

What would your advice be to someone just starting out in the field?

I would first advise them not to listen to conventional wisdom in their field. Some of our most influential discoveries were made through ‘ignorance’ of what should or shouldn’t work. That said, my next best advice is to find your community and build your network of mentors, collaborators, friends and colleagues. This is so important, both scientifically, and psychologically, and I think is sometimes under appreciated by young researchers.

What advances do you hope to see in your field over the next decade?

Targeted covalent inhibitors are already becoming mainstream in drug discovery (this is very far from where they were when I got into the field and they still have some way to go). Yet, there are still very few electrophiles that are precedented in approved drugs. I hope over the next decade to see new electrophiles make it into approved drugs, expanding the scope of covalent inhibitors.

Read Nir London’s contributions to the field through their ACS published research.

Learn about winners of previous ICBS Rising Star awards, supported by ACS Publications.

The Nobel Prize in Chemistry 2021 Goes to Benjamin List and David W. C. MacMillan

The Nobel Prize in Chemistry 2021 is awarded jointly to Benjamin List and David W. C. MacMillan for their work in “the development of asymmetric organocatalysis,” a method that uses small organic molecules as catalysts instead of enzymes or metals. This innovation in molecular construction has led to catalysts that are less expensive and more environmentally friendly, while also opening up new pathways in pharmaceutical research.

“Asymmetric organocatalysis offers a new way of thinking and a more sustainable way of carrying out crucial chemical reactions,” said ACS President H. N. Cheng. “In the big picture, the ability to create new compounds to address human problems is the strength of chemistry. Chemists are like magicians, and with asymmetric organocatalysis, we have a new magic wand for making important drugs.”

Both winners have long histories with the ACS. List has been a member of ACS for 21 years; MacMillan for 26. List has been honored by the ACS with both the 2022 Herbert C. Brown Award for Creative Research in Synthetic Methods and the Arthur C. Cope Scholar Award in 2014. MacMillan won the Gabor A. Somorjai Award for Creative Research in Catalysis in 2018, the ACS Award for Creative Work in Synthetic Organic Chemistry in 2011, the Arthur C. Cope Scholar Award in 2007, and the Elias J. Corey Award for Outstanding Original Contribution in Organic Synthesis by a Young Investigator in 2005.

Benjamin List and David W. C. MacMillan have each published many articles in ACS Publications journal over the years. The following articles from each of the laureates will be made free-to-read for 30 days, starting October 6, 2021, in honor of their win.

Benjamin List

Asymmetric Enamine Catalysis
Chem. Rev. 2007, 107, 12, 5471–5569
DOI: 10.1021/cr0684016

Aldolase Antibodies of Remarkable Scope
J. Am. Chem. Soc. 1998, 120, 12, 2768–2779
DOI: 10.1021/ja973676b

The Direct Catalytic Asymmetric Three-Component Mannich Reaction
J. Am. Chem. Soc. 2000, 122, 38, 9336–9337
DOI: 10.1021/ja001923x

Direct Catalytic Asymmetric α-Amination of Aldehydes
J. Am. Chem. Soc. 2002, 124, 20, 5656–5657
DOI: 10.1021/ja0261325

Enamine Catalysis Is a Powerful Strategy for the Catalytic Generation and Use of Carbanion Equivalents
Acc. Chem. Res. 2004, 37, 8, 548–557
DOI: 10.1021/ar0300571

Proline-Catalyzed Direct Asymmetric Aldol Reactions
J. Am. Chem. Soc. 2000, 122, 10, 2395–2396
DOI: 10.1021/ja994280y

David W. C. MacMillan

New Strategies for Organic Catalysis:  The First Enantioselective Organocatalytic 1,3-Dipolar Cycloaddition
J. Am. Chem. Soc. 2000, 122, 40, 9874–9875
DOI: 10.1021/ja005517p

New Strategies in Organic Catalysis:  The First Enantioselective Organocatalytic Friedel−Crafts Alkylation
J. Am. Chem. Soc. 2001, 123, 18, 4370–4371
DOI: 10.1021/ja015717g

New Strategies for Organic Catalysis:  The First Highly Enantioselective Organocatalytic Diels−Alder Reaction
J. Am. Chem. Soc. 2000, 122, 17, 4243–4244
DOI: 10.1021/ja000092s

The Enantioselective Organocatalytic 1,4-Addition of Electron-Rich Benzenes to α,β-Unsaturated Aldehydes
J. Am. Chem. Soc. 2002, 124, 27, 7894–7895
DOI: 10.1021/ja025981p

The First Enantioselective Organocatalytic Mukaiyama−Michael Reaction:  A Direct Method for the Synthesis of Enantioenriched γ-Butenolide Architecture
J. Am. Chem. Soc. 2003, 125, 5, 1192–1194
DOI: 10.1021/ja029095q

Enantioselective α-Arylation of Aldehydes via Organo-SOMO Catalysis. An Ortho-Selective Arylation Reaction Based on an Open-Shell Pathway
J. Am. Chem. Soc. 2009, 131, 33, 11640–11641
DOI: 10.1021/ja9026902

Read More About the Nobel Prize in Chemistry 2021 in C&EN.

The Nobel Prize in Physiology or Medicine 2021 Goes to David Julius and Ardem Patapoutian

Professor David Julius at the University of California, San Francisco and Professor Ardem Patapoutian, at Scripps Research in California won the 2021 Nobel Prize in Physiology or Medicine “for their discoveries of receptors for temperature and touch,” both of which are essential to our ability to navigate, understand, and interact with the world.

The pair will receive equal shares of the $1.1 million prize for their work exploring the molecular basis for our bodies’ ability to sense temperature and pressure. Their work on the ion channels that react to heat, cold, and mechanical force has also opened up research opportunities in a number of clinical areas, including treating pain, cancer, and asthma.

Professor Patapoutian has published the following articles in ACS Publications journals. In recognition of his win, these articles will be made free-to-read for 30 days, starting Oct. 4, 2021.

Discovery, Optimization, and Biological Evaluation of 5-(2-(Trifluoromethyl)phenyl)indazoles as a Novel Class of Transient Receptor Potential A1 (TRPA1) Antagonists
J. Med. Chem. 2014, 57, 12, 5129–5140
DOI: 10.1021/jm401986p

***

A FAAH-Regulated Class of N-Acyl Taurines That Activates TRP Ion Channels
Biochemistry 2006, 45, 30, 9007–9015
DOI: 10.1021/bi0608008

***

Read more about the winners of the 2021 Nobel Prize in Physiology or Medicine in C&EN, as well as coverage of Julius and Patapoutian’s win of the 2020 Kavli Prize in Neuroscience.

Meet the 2021 Analytical Chemistry Young Innovator Award Recipient: Professor Robbyn K. Anand

Professor Robbyn K. Anand, an Assistant Professor in the Department of Chemistry at Iowa State University, is the recipient of the 2021 Analytical Chemistry Young Innovator Award.

Co-sponsored by Analytical Chemistry and Chemical and Biological Microsystems Society (CBMS), this annual award honors early-career researchers who demonstrate exceptional technical advancement and innovation in the field of microfluidics or nanofluidics. Professor Anand will receive an award plaque and an honorarium of US $2,500.

“I feel deeply honored because I respect and admire the leaders who have established this field. I am also immensely proud of my students, who impress me daily with their dedication and ingenuity. I view this recognition as a call to train the next generation of innovators in microfluidics and nanofluidics,” says Professor Anand.

Get to Know Professor Anand

Professor Anand’s research integrates electrochemical sensing, electrokinetic focusing, and cellular dielectrophoresis with microfluidics to address critical needs in human health. The goal of her research is to broaden access to diagnostic information at the point of need, thereby allowing physicians to provide more timely and better tailored therapeutic interventions, ultimately improving outcomes for patients.

Professor Anand joined the Department of Chemistry at Iowa State University as an Assistant Professor in August 2015. She was introduced to microfluidics by Professor Richard M. Crooks at the University of Texas at Austin during her doctoral work, which focused on the development of electrochemical methods to generate electric field gradients that drive enrichment and separation of trace analytes. As a postdoctoral fellow at the University of Washington, she worked with Professor Daniel T. Chiu to advance methods for the isolation of circulating tumor cells.

Over the last several years, her group has developed microfluidic platforms for ‘liquid biopsy’ to aid in cancer diagnosis and to inform treatment decisions. One such technology facilitates selective and individual isolation of circulating tumor cells from peripheral blood, thereby allowing for the identification of cell-to-cell differences that drive cancer progression and response to therapy. Another device electrokinetically enriches circulating cell-free nucleic acids and facilitates subsequent label-free electrochemical detection of targeted sequences. These platforms have been designed to minimize the need for peripheral equipment and manual intervention by the operator.

“Our approach to these diagnostic challenges is to span our efforts from fundamental advancements to clinical application, which creates opportunities for broad impact. For example, in response to the recent global crisis, we have adapted the new approach that we developed for circulating tumor DNA detection for sensitive and low-cost quantification of viral RNA. Advancing science while addressing real-world problems is highly rewarding,” says Professor Anand.

Read an Interview with Professor Anand:

I caught up with Professor Anand recently to learn more about her research and what’s next for her and her research group. I’ve provided highlights from our conversation below.

What advice would you give to upcoming researchers in the field?

Think of yourself broadly as a scientist and avoid defining yourself too narrowly. There is a lot of room for innovation at the interfaces between distinct STEM fields, and many current challenges require a multidisciplinary approach to be solved effectively. Therefore, an ability to communicate, collaborate and innovate across these boundaries will maximize your potential for impact.

Do you have an ACS paper that you would like to share? Why did you choose this one?

Here is a paper that we published in the Journal of the American Chemical Society. As a result of this work, we fundamentally advanced droplet biotechnology by creating a path to perform functions on preformed droplets that were previously inaccessible. The methods that we developed can be leveraged for controlled delivery of reagents and the enrichment and separation of droplet components. We are excited about the potential for cross-cutting impact in areas ranging from single-entity bioassays to droplet-templated particle synthesis.

Concentration Enrichment, Separation, and Cation Exchange in Nanoliter-Scale Water-in-Oil Droplets
J. Am. Chem. Soc. 2020 142 (6), 3196-3204.
DOI: 10.1021/jacs.9b13268

How will your work benefit society?

The pandemic has underscored the importance of detailed and timely diagnostic information, which allows patients and physicians to make better informed decisions about what action to take. This crisis has also increased the awareness of the global community about limitations in access to diagnostics with respect to the speed, cost, sensitivity, shelf-life, and need for specialized equipment. The platforms that we develop, whether for viral or cancer diagnostics, address these barriers to reduce delays and inequities in healthcare.

What’s next in your research?

We are both moving towards translation by vetting the platforms we have developed clinically, for example, in the diagnosis and monitoring of melanoma, and working to understand fundamental aspects of these systems more deeply so that we can continue to innovate. Collaborations with my colleagues in chemistry and engineering here at Iowa State as well as the Holden Comprehensive Cancer Center at the University Iowa are essential to those efforts.

Why do you choose to publish in Analytical Chemistry?

I publish in Analytical Chemistry because of its long-standing and consistent record of excellence and the opportunity to connect with a readership at the forefront of measurement science.

Is there anything else that you would like to share?

I would like to take this opportunity to thank Analytical Chemistry for supporting early career scientists like myself and to impress upon the readers the importance of mentorship. My journey as a scientist began because I happened upon a poster advertising a National Science Foundation Research Experience for Undergraduates (NSF-REU), which led me to work for a summer in 2002 with Professor James A. Cox at Miami University of Ohio. The impact that this research experience had on my scientific career has taught me how valuable it is to invest our time and resources in young scientists.

Winners Announced for the 2020 Arthur E. Schwarting and Jack L. Beal Awards for Best Papers in the Journal of Natural Products

The Journal of Natural Products, in partnership with the American Society of Pharmacognosy (ASP), is thrilled to announce the 2020 winners of the Arthur E. Schwarting and Jack L. Beal Awards.

This initiative was launched in 2001 by the Foundation Board of ASP to recognize some of the best work published in the Journal of Natural Products on an annual basis, in fond remembrance of two distinguished former editors of the journal.

  • The Arthur E. Schwarting Award is open to all papers published in the journal within a given year.
  • The Jack L. Beal Award is given to early-career investigators (within 12 years of receiving their Ph.D. or within 10 years of gaining their first professional appointment, such as Assistant Professor or an equivalent position in industry or government).
  • A two-tiered process is used each year to determine the winners: Journal of Natural Products Editors nominate eight papers for the awards, and the ASP President appoints an ad hoc committee to make the final selections.

2020 Jack L. Beal Award-Winning Paper

Synthesis and Biological Evaluation of Tryptamines Found in Hallucinogenic Mushrooms: Norbaeocystin, Baeocystin, Norpsilocin, and Aeruginascin
Alexander M. Sherwood*, Adam L. Halberstadt, Adam K. Klein, John D. McCorvy, Kristi W. Kaylo, Robert B. Kargbo, and Poncho Meisenheimer
J. Nat. Prod. 2020, 83, 2, 461–467
DOI: 10.1021/acs.jnatprod.9b01061

Interview with Awardee Alexander Sherwood of Usona Institute:

What is the significance of the 2020 Beal Award-winning paper?
The report aimed to provide the first step toward understanding if other tryptamine natural products present in psychedelic mushrooms, apart from psilocybin and psilocin, could also possess psychoactive properties. To enable pharmacological study, we developed synthetic methods that solved a few challenges associated with isolating purified solid zwitterionic phosphorylated tryptamines. The pharmacological data indicated that while active at the serotonin-2A receptor, the tested compounds may not efficiently reach the brain to elicit a psychoactive effect. This was one of the first published works from Usona’s psychedelic research laboratory, and we are honored to see that it has brought attention and inquiry to these fascinating natural products.

What are some future directions for the research reported in the winner paper?
One area of interest is understanding the extent to which the dynamic mix of tryptamines in psychedelic mushrooms might impact potential subjective and adverse effects. Utilizing the synthesized tryptamines, experiments focused on pharmacokinetics, metabolism, and toxicology are intended to provide insight into these questions.

 What is your favorite aspect of natural products research?
Nature will always be the most innovative chemist, and many of our most elegantly designed medicines are rooted in the study of natural products.  With regard to CNS-drug design, natural products have offered countless non-intuitive molecular templates whose chemical intricacy and pharmacological precision often outshine the most advanced efforts of contemporary drug discovery.

2020 Arthur E. Schwarting Award-Winning Paper

Bioreductively Activatable Prodrug Conjugates of Combretastatin A-1 and Combretastatin A-4 as Anticancer Agents Targeted toward Tumor-Associated Hypoxia
Blake A. Winn, Laxman Devkota, Bunnarack Kuch, Matthew T. MacDonough, Tracy E. Strecker, Yifan Wang, Zhe Shi, Jeni L. Gerberich, Deboprosad Mondal, Alejandro J. Ramirez, Ernest Hamel, David J. Chaplin, Peter Davis, Ralph P. Mason, Mary Lynn Trawick*, and Kevin G. Pinney*
J. Nat. Prod. 2020, 83, 4, 937–954
DOI: 10.1021/acs.jnatprod.9b00773

Interview with joint Awardees Kevin Pinney and Mary Lynn Trawick of Baylor University

Professor Kevin Pinney, Baylor University

What does the 2020 Schwarting Award mean to you?
We are extremely honored to have been selected as recipients of the 2020 Arthur E. Schwarting Award for our co-authored 2020 publication in the Journal of Natural Products. It is especially noteworthy that this award honors and celebrates the outstanding legacy of Professor Arthur E. Schwarting, who made life-long seminal contributions to the field of natural products research and thus significantly advanced this area of research inquiry.

While the award is presented by the American Society of Pharmacognosy (ASP), it is shared by the American Chemical Society (ACS) through a unique partnership between the ASP and the ACS that supports the publication of the Journal of Natural Products. Thus the award also celebrates this highly productive collaboration between these two outstanding professional societies (APS and ACS). For us, the award represents a celebration of the shared efforts reflected through the invaluable contributions of the co-authors of this publication. Each of these individuals made uniquely important contributions that collectively reflect a wide range of scientific inquiry, including synthetic organic chemistry, biochemistry, cell biology, imaging, and drug discovery and development.

What draws you to research involving natural products?
Natural products present a rich pharmacopeia of structurally diverse molecules that often demonstrate promising profiles of biological activity. Nature provides incredible chemical and biological diversity of compounds that can be used as leads for drug development. As such, natural products, along with structurally modified analogs and derivatives, continue to serve as lead therapeutic candidates in a myriad of drug discovery and development campaigns.

It is a special privilege of ours that the natural products showcased in this manuscript, combretastatin A-4 (CA4) and combretastatin A-1 (CA1), were discovered and pioneered by Professor George R. Pettit (Arizona State University), who is world-renowned as a highly prolific and influential scholar. Professor Pettit has dedicated much of his life’s work toward the eradication of cancer. His research has resulted in the discovery and advancement of many promising natural products (along with associated analogs) as potential therapeutic agents for the treatment of cancer, and his work has inspired future generations of scientists to pursue careers that include natural products and cancer treatment as highlighted themes. It is a further honor to know Professor Robert (Bob) Pettit both as a collaborator and a friend, and we have celebrated this relationship through a tribute to Bob Pettit in this manuscript.

How did the collaboration between the Pinney and Trawick Research Groups come about?

Professor Mary Lynn Trawick, Baylor University

The collaboration between our two research groups (the Pinney Group: organic and medicinal chemistry and the Trawick Group: biochemistry and cell biology) started with research on tubulin-binding molecules as anticancer agents. This program focused on small-molecule inhibitors of tubulin polymerization with an emphasis on vascular disrupting agents (colchicine-site, tubulin-binding molecules that resulted in tumor vasculature shutdown) and involved aspects of fundamental discovery science as well as efforts towards translational development of therapeutic agents for the treatment of cancer. A number of molecules that emerged from our collaborative program demonstrated potent cytotoxicity against human cancer cell lines and also preliminary in vivo efficacy. Ongoing studies have focused on strategies to take advantage of the potency of these compounds while improving their selectivity for the tumor microenvironment, and in this regard, we initiated a program in collaboration with Dr. David (Dai) Chaplin (then at OXiGENE Inc.) over a decade ago on prodrugs that could be bioreductively activated in hypoxic tumors. Inspiration for these studies was fueled by the previous advancement of tirapazamine to clinical trials, along with the early pioneering work by Dr. Peter Davis related to hypoxia-activated combretastatin prodrugs, and the encouragement by Dr. Chaplin in regard to potential therapeutic translation.

What are the attributes of your 2020 Journal of Natural Products publication?
The chaotic tumor vasculature, characterized by impaired microcirculation and increased diffusional distances combined with rapid tumor growth, results in a lack of oxygen or hypoxia in many tumor cells. Hypoxia in tumors and cancer cells leads to genetic instability with increased conversion of the epithelial to a mesenchymal phenotype, promoting tumor cell proliferation, migration, and metastasis. Hypoxic tumors undergo a signaling and metabolic transformation, becoming more resistant to both chemotherapy and radiotherapy. In general, tumor hypoxia is associated with poor clinical outcomes. Therefore targeting hypoxic cells in tumors with potent anticancer agents offers an opportunity for enhanced selectivity with antimetastatic potential. The bioreductively activatable prodrug conjugates (BAPCs) advanced in this publication are based on the natural products CA4 and CA1, which are structurally similar with the distinction that CA1 bears an orthodihydroxy functionality in the aromatic B-ring whereas CA4 features a single phenolic moiety.

What are the next steps for this research?
Preliminary in vivo pharmacodynamic and pharmacokinetic studies conducted in collaboration with Dr. Ralph P. Mason (University of Texas Southwestern Medical Center) are quite promising, but more detailed studies are required. These studies would greatly benefit from improved aqueous solubility of our bioreductive prodrugs. Enhanced targeting through cleavable protein conjugates that bind to specific cell surface tumor markers represents another priority in this work. In addition, numerous other small-molecule analogs have been designed, synthesized, and evaluated for their cytotoxicity (in our laboratories) and for their ability to function as inhibitors of tubulin polymerization through a long-standing collaboration with Dr. Ernest Hamel (National Cancer Institute), who also serves as a co-author of this publication. The most promising of these molecules will be prepared as their corresponding BAPCs for further biological evaluation.

Read the Building Chemical Bonds Virtual Issue