From Bench-to-Bench and Beyond: Engaging People with High Impact Chemistry

Tuesday, August 23, 2016

Location: Room 204B Philadelphia Convention Center 


Morning Session

09:00-09:05 Introductory Remarks
09:05-09:30 William Morris
Development of manufactory route for MK-8931
 09:30-10:05  Timothy F. Jamison
 Synthesis design through the lens of flow chemistry
– how, when, and why
 10:05-10:40  Helen E. Blackwell
Intercepting and delineating bacterial communication
pathways using synthetic ligands
 10:40-11:00  Refreshment Break
 11:00-11:35  Richard Friesner
 From quantum chemistry to drug discovery: the evolution
of Schrodinger, Inc. the world of computation chemistry
11:35-12:10 Ryan A. Mehl
Expanding chemical biology with genetic code expansion

Afternoon Session

13:30-13:35 Introductory Remarks
Chris Hewitt
BASF Science Relations Manager, North America
 13:35-14:10 Martin D. Burke
 3D printing molecular prosthetics
 14:10-14:45  Samuel I. Stupp
 Supramolecular soft materials for energy and medicine
 14:45–15:05  Refreshment Break
 15:05-15:40 Nora S. Radu
 Design of materials for organic light-emitting diode displays
 15:40–16:15  Paulo E. Arratia
 Rheology on a chip
16:15–17:00 Discussion Panel



William Morris

Process Chemistry, Merck Research Laboratories, Rahway, NJ, United States.

Development of a manufacturing route for MK-8931

Alzheimer’s disease (AD) is a neurodegenerative disorder that results in gradual loss of memory and impairment of vocal and motor control before ultimately resulting in death. It is estimated that by 2030 approximately 75 million individuals worldwide will be suffering from AD, a number that represents a 60% increase from the number of people living with the disease in 2015. To address this unmet medical need, Merck has advanced MK-8931, an investigational β-amyloid precursor protein site-cleaving enzyme (BACE) inhibitor, into Phase III clinical trials for the treatment of AD. The evolution of the synthetic route to support the preclinical and clinical development of MK-8931 will be described, including our most recent advances to address the process development challenges observed in earlier synthetic approaches to MK-8931.


Timothy F. Jamison

Chemistry/18-590, MIT, Cambridge, MA, United States.

Synthesis design through the lens of flow chemistry – how, when, and why

Flow chemistry has the potential to revolutionize the synthesis of organic molecules – operationally and conceptually. Flow systems can reduce reaction times, increase efficiency, and obviate problems often encountered in scaling up. In addition to these important practical advantages, flow chemistry expands the “toolbox” of organic reactions available to scientists engaged in the synthesis of molecules – from small-scale experiments to large-scale production. These benefits are a direct result of several features of flow synthesis that batch synthesis typically cannot achieve, for example, the ability to control fluid flow precisely, the access to temperature and pressure regimes not usually considered to be practical, and the enhanced safety characteristics of flow chemical systems. In this lecture we will discuss some of our investigations in this area in the form of case studies, wherein a specific target or family of organic molecules has served as an inspiration for the development of new methods of organic synthesis in flow. The primary thesis we will discuss is that the collection of innovations in flow chemistry has changed the way we consider building molecules. That is, it is both a technological and conceptual advance in chemical synthesis.


Helen E. Blackwell 

Michael A. Welsh, Joseph D. Moore, Michelle E. Boursier, Tian Yang, Matthew C. O’Reilly, Kayleigh E. Nyffeler, Joseph K. Vasquez, Helen E. Blackwell

Chemistry, University of Wisconsin-Madison, Madison, WI, United States.

Intercepting and delineating bacterial communication pathways using synthetic ligands

Bacteria can utilize chemical signals to coordinate the expression of group-beneficial behaviors in a mode of cell-cell communication called quorum sensing (QS). Once a quorate population of bacteria is achieved in a given environment, bacteria will work together as a group to initiate behaviors that are impossible as individual cells. The discovery that QS controls the production of virulence factors and biofilm formation in many common human pathogens has driven an explosion of research aimed at both deepening our basic understanding of these regulatory networks and developing chemical agents that can modulate QS signaling. The inherently chemical nature of QS makes studying these pathways with small molecule tools a complementary approach to traditional microbiology techniques. In fact, chemical tools are beginning to yield new insights into QS regulation and provide new strategies to inhibit QS. In this presentation, we will outline our general research approach to the design of synthetic ligands capable of blocking or activating QS in a range of Gram-negative and Gram-positive bacteria. Recent examples of how we have used these ligands to reveal new knowledge of QS biology will be highlighted. We will also detail outstanding challenges in the field and suggest strategies to overcome these issues.


Richard A. Friesner

Columbia University, New York, NY, United States.

From quantum chemistry to drug discovery: the evolution of Schrodinger, Inc. in the world of computational chemistry

We will discuss the evolution of Schrodinger, Inc. from a small company distributing a single quantum chemistry program to its current status as a comprehensive provider of computational chemistry solutions, and a collaborative participant in drug discovery projects. Major challenges in scientific development, software engineering, business strategy and execution, and fundraising had to be overcome in order to successfully grow the company to its present size of 280 employees, including more than 100 Ph. D. computational scientists. A major headwind to success was the disappointment in industry with the efficacy of physics based simulation throughout the 1980’s and 1990’s. The increasing power of computational hardware (in particular GPUs), combined with more mature algorithms and computational models, is now revolutionizing the field, to the point where many pharmaceutical and biotechnology companies are considering a major investment in biomolecular simulation. This strategic inflection point is creating many exciting opportunities for Schrodinger and other developers, including academic groups.


Ryan A. Mehl

Department of Biochemistry Biophysics, Oregon State University, Corvallis, OR, United States.

Expanding chemical biology with genetic code expansion 

How would you like to tune the reactivity of your protein? Genetically encoded, site-specific incorporation of non-canonical amino acids (ncAAs) provides unprecedented molecular control over proteins and provides access to countless creative chemical biology applications. Genetic Code Expansion requires that a cell’s translational machinery be expanded to include new orthogonal tRNA/tRNA-synthetase pairs specific for new ncAAs. The challenges in reengineering translation and applying this powerful technology for new chemical biology users will be discussed.

The mission of the Unnatural Protein Facility at Oregon State University is to assist in training new users and providing access to new chemical biology tools The UP Facility workshops and conference on Genetic Code Expansion will also be discussed.


Martin D. Burke

University of Illinois Urbana Champaign, Urbana, IL, United States.

3D printing molecular prosthetics

The talk will describe recent efforts to create a 3D printer for molecules that enables the development of prostheses on the molecular scale (and many other types of small molecules that perform high-impacting functions).


Samuel I. Stupp

Northwestern University, Evanston, IL, United States.

Supramolecular soft materials for energy and medicine

Supramolecular materials have the potential to mimic the structures and dynamics of biological systems, and it is therefore a rich platform for the development of bio-inspired materials. The interesting features of supramolecular soft materials include, nanoscale control of dynamics, highly responsive behavior to external stimuli, capacity to self-heal defects, noncovalent co-localization of functional domains, and the use of self-assembly to optimize function, among many others. The development of these materials poses a great challenge to chemists since it requires the integration of many fields including synthetic organic chemistry, supramolecular chemistry, materials science, physical chemistry, and computational chemistry, among others. This lecture will describe supramolecular soft materials that mimic the photosynthetic machinery in biological systems by integrating the necessary functions to generate solar fuels. As a second topic, the lecture will discuss the development of bioactive supramolecular materials for biomedical targets such as regenerative medicine and the development of targeted therapies.


Nora S. Radu

Nora S. Radu, Gene Rossi, Frederick Gentry, Norman Herron, Tiffany N. Hoerter

DuPont, Wilmington, DE, United States.

Design of materials for organic light-emitting diode displays

Organic light emitting diode (OLED) technology enables for more vivid color, higher contrast, faster response, thinner panels, a wider viewing angle and lower power consumption than traditional liquid crystal displays. We will present our recent progress in designing small molecule and polymeric materials that will enable display manufacturers to deliver superior OLED device performance with lower manufacturing costs for large-format displays.


Paulo E. Arratia

University of Pennsylvania, Philadelphia, PA, United States.

Rheology on a chip

The concentration of fluids plays a significant role in their behavior. For example, the small quantity of proteins found in blood plasma make the fluid much more viscous than water. Instruments for measuring viscosity require precise calibration due to kinetic influences such as shear and inertia of suspended media. Scaling down these studies to microfluidic chips limits these kinetic factors, thus improving precision and reducing costs. We will precent our work developing these microfluidic cells, as well as the use of low-inertia fluids to create 3D arrays of fluid microdomains.