Events in organic chemistry.

Covalent Small-Molecule Inhibition of KRAS: From Concept to Clinic

Abstract: KRAS is one of the most frequently mutated oncogenes in human cancer.  Despite more than three decades of research, indirect approaches targeting KRAS-mutant cancers have largely failed to show clinical benefit, and direct approaches have been stymied by the apparently ‘undruggable’ nature of KRAS.  I’ll describe efforts at Amgen to identify cysteine-reactive molecules capable of selectively inhibiting a prevalent KRAS mutation, KRASG12C.  These efforts leveraged iterative screening and structural biology studies, property-based optimization, and

Deconstructing Macromolecules

Polymers are arguably the most important materials on Earth. Despite a century of study, however, much remains unknown about how the molecular-scale features of polymers translate to bulk properties, preventing predictive design of next-generation materials. This talk will highlight our efforts to install cleavable bonds into precise locations within macromolecules, showing how we can use selective bond cleavage to unveil previously hidden features of polymer structure and enable new material functions.

From Heterocycles to Heteroatom Transfer: radical approaches for chemical synthesis

Abstract: The selective generation and controlled reactivity of open-shell reactive species continues to serve as inspiration for new reaction development in chemical synthesis. This talk will describe recent advances using phosphorous-based reagents to generate carbon- and heteroatom-centered radicals via sequential atom-transfer radical additions as well as the use of copper compounds engaged in light-mediated metal-ligand co-operativity to harness and activate non-conjugated alkenes towards photocycloadditions.

Synthetic biology approaches to study and exploit RNA regulation

Abstract: RNA transcribed from the genome in the nucleus bears little resemblance to the RNA polymer it will ultimately become in the cytoplasm where it is translated into protein. Well-known processes such as capping, splicing and polyadenylation, as well as the recently discovered and ever-expanding list of diverse chemical modifications and editing, significantly alter the properties and fates of a given RNA during the course of its lifetime. These alterations regulate critical aspects of RNA function such as stability, transport, protein binding, and translation.

SCREENING: Percy Julian: Forgotten Genius

To Celebrate Black History Month, the Department of Chemistry is presenting special screening of “Percy Julian: Forgotten Genius” a biopic about a trailblazing Black scientist who earned a place in the parthenon of scientific greatness despite facing horrific racism throughout his life — including at prestigious academic institutions. Dr. Julian was the first Black chemist elected to the National Academy of Sciences (only the second African-American scientist to receive the honor), and was awarded >130 patents in chemistry. The first to synthesize the natural product physostigmine, Dr.

Philicities, Fugalities, and Equilibrium Constants: A Quantitative Approach to Polar Organic Reactivity

Our understanding of polar organic reactivity is based on relationships between rate and equilibrium constants. Thus, strong bases are generally considered to be good nucleophiles as well as poor nucleofuges. Though exceptions from this general rule have long been known, a systematic analysis has been problematic, because rate constants for the reactions of nucleophiles with C-centered electrophiles have often been correlated with Brønsted basicities (i. e., affinities towards the proton).

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