In everyday life, containers serve many important purposes. For example, containers are used to preserve foods and beverages, to ship items to various locations around the globe, and to protect their contents from the outside elements. Molecules also need containers for many reasons; Dr. Lyle Isaacs of the University of Maryland, is working to synthesize some of the world’s newest molecular containers with the power to change the chemical properties of the compounds they encapsulate and increase their utility in multiple applications. Pharmaceutical research is often crippled by the discovery of crucial drugs that cannot be delivered due to their insolubility in water, but when placed in the right container, these molecules become soluble and can then be distributed to the necessary places within the body. Cyclodexrins are a common type of molecular container facilitating the production of $5 billion of these insoluble drugs per year. Dr. Isaacs and his team have found that cucurbit[n]uril containers (also called CB[n]) possess properties that would allow them to improve upon a number of applications that cyclodextrin, as well as other molecules, fail to fully service, such as the formulation of new, advanced drugs. Another application involves neuromuscular blocking agents (NMBAs), which are administered by anesthesiologists during surgery, but which pose multiple threats to patients after surgery. Muscle weakness and difficulty breathing are only two of the side effects that increase healthcare costs and patient mortality. The Isaacs group is developing CB[n]-type receptors as reversal agents to significantly reduce the undesirable consequences of residual effects of NMBAs. This work promises to impact the care of the 18.7 million patients who receive NMBAs each year in the United States.

Dr. Isaacs is a highly-cited researcher with an immense passion for pushing the frontier of chemistry as well as fostering the next generation of chemists to carry on their own searches for new exciting molecules. He takes his position as an educator to heart by supporting all of his students’ own personal interests and helping them meet their goals. For those with their heart set on leading their own research in the future, Dr. Isaacs guides them toward the high-impact publications and experience they need to be competitive in the field; for those interested in chemistry education, he teaches them to be good mentors early on by pairing older students up with younger ones. Dr. Isaacs’ is the Director of the University of Maryland's Chemistry Graduate Assistance in Areas of National Needs (GAANN) program sponsored by the US Department of Education.

Research in the Isaacs Lab targets an improved understanding of the basic science behind CB[n] molecular containers with the goal of using this knowledge to create new molecular containers for real-world biomedical applications:

• Turning Insoluble Developmental Drugs into Soluble Medicines: As medicinal research steers closer to inventing new drug compounds with the capacity to benefit human life, an estimated 40-70% of these critical new drugs are found to be so insoluble in water that they cannot be formulated on their own. By designing and synthesizing broadly-applicable CB[n]-type molecular containers as solubilizing excipients, the probability for new drugs to reach the market will be dramatically improved.
• Reversing Neuromuscular Blocks: CB[n]-type molecular containers have also exhibited the capacity to reverse the unwanted side effects of neuromuscular block induced by NMBAs that are commonly used during anesthesia / surgery. To better bind to and thereby sequester  these NMBAs from the bloodstream, the binding affinity between Dr. Isaacs’ molecular containers and NMBAs as well as the containers’ selectivity must be studied in further detail. Compounds with appropriate levels of affinity and selectivity will then proceed to relevant in vitro and in vivo tests.
• Targeted Delivery of Anti-Cancer Agents: By designing new containers that both encapsulate anti-cancer agents and are actively targeted to cancer cells and tumors, Dr. Isaacs and his research group aim to improve the efficacy and reduce the side effects of anti-cancer agents.  Using this technique, which has been proven to increase the in-vitro bioactivity of the anti-cancer agents oxaliplatin by 10-fold, Dr. Isaacs is aiming to expand the range of different anti-cancer drugs that will now have an effective route of targeted delivery.
• Building the Foundations of Molecular Container Chemistry: Advancing biomedical applications would not be possible without the basic theory laid out and fundamental mechanisms understood. As synthetic chemists, Dr. Isaacs and his group are continuously exploring deeper into the field of molecular container chemistry and paving the way for new molecules to be discovered and synthesized. A few of the studies they are conducting involve replacing certain compounds used commonly in many analytical tests of biochemistry - such as avidin-biotin - with their own CB[n] complexes, which are smaller, more robust, and stimuli responsive.