Integrated Calendar

The mathematical analogy between information and thermodynamical entropy has recently led to promising developments in chemistry and physics, and information theory tools are increasingly important in chemical and biological data analysis. In this talk I will describe a few of our ideas at the intersection of physical chemistry, information theory, and computer science, with the focus on single-molecule data analysis. Single-molecule experimental studies have opened a new window into the elementary biochemical steps, function of molecular machines, and cellular phenomena. The information contained in single-molecule trajectories is however often underutilized in that oversimplified models such as one-dimensional diffusion or one-dimensional random walk are used to interpret experimental data. I will show that much finer details of single-molecule dynamics, such as conformational memory and static disorder, can be deduced from an analysis that is similar to Shannon’s analysis of printed English; in particular, this method relates conformational memory to the information-theoretical compressibility of single-molecule signals.

Over the past decade, there has been tremendous progress in the measurement, modeling and understanding of structure-function relationships in single molecule circuits. Experimental techniques for reliable and reproducible single molecule junction measurements have led, in part, to this progress. In particular, the scanning tunneling microscope-based break-junction technique has enabled rapid, sequential measurement of large numbers of nanoscale junctions allowing a statistical analysis to readily distinguish reproducible characteristics. Although the break-junction technique is mostly used to measure electronic properties of single-molecule circuits, in this talk, I will demonstrate its versatile uses to understand both physical and chemical phenomena with single-molecule precision. I will discuss some recent experimental and analysis aimed at understanding quantum interference in single-molecule junctions. I will then show an example where molecular structure can be designed to utilize interference effects to create a highly non-linear device. Finally, I will discuss some new areas of research aiming to demonstrate that electric fields can catalyze chemical reactions.

Small molecule inhibitors and drugs that are able to form a covalent bond with
their protein target have several advantages over traditional binders. While they were
avoided for a long time due to concerns of specificity, in recent years they are attracting
significant interest as underscored by FDA approvals of rationally designed covalent
drugs, such as Ibrutinib and Afatinib. In the past few years my research team has been
focused on technology development for the field of Covalent Ligand Discovery. These
include: covalent virtual screening, empirical covalent fragment screening, the first
reported reversible covalent targeted degraders (PROTACs), and most recently the
discovery of new chemistry that enables the design of superior covalent binders. These
technologies enabled the discovery of novel, potent inhibitors for several challenging
targets. These inhibitors, in turn, have shed new light on the target’s biological function
and represent potential therapeutic leads. I will describe our journey from the original goal
of mere ‘discovery’ of covalent binders to the current challenge of functionalizing covalent
binders for various applications.

Solid-state NMR has become an essential tool for structural characterisation of materials,
in particular systems with poor crystallinity and structural disorder. In recent years, a surge of
interest has been observed for the study of paramagnetic systems, in which the interaction between
nuclei and unpaired electrons allows to probe the electronic structure and properties of materials
more directly. However, simultaneously this interaction leads to very broad resonances, which are
dicult to acquire and interpret. While signicant advancements in both NMR instrumentation
and methodology have paved the way for the study of spin I = 1=2 nuclei in these systems, still
many issues remain to be resolved for routine investigation of quadrupolar nuclei I > 1=2. Here we
focus on improving both the excitation of the broad resonances and the resolution in the spectra
of spin I = 1 nuclei. The latter problem is addressed by developing methods for separation of the
shift and the quadrupolar interactions. We introduce two new methods under static conditions,
which have the advantage over previous experiments of both suppressing spectral artefacts and
exhibiting a broader excitation bandwidth. Furthermore, we demonstrate for the rst time an
approach for separation of the anisotropic parts of the shift and quadrupolar interaction under
magic-angle spinning. Secondly, to achieve broadband excitation we develop a new theoretical
formalism for phase-modulated pulse sequences in rotating solids, which are applicable to nuclear
spins with anisotropic interactions substantially larger than the spinning frequency, under conditions
where the radio-frequency amplitude is smaller than or comparable to the spinning frequency. We
apply the framework to the excitation of double-quantum spectra of 14N and design new pulse
schemes with
-encoded properties. Finally, we employ the new sequences together with density
functional theory calculations to elucidate the electron and hydride ion conduction mechanisms in
barium titanium oxyhydride.

Charge transfer and transport processes through molecular interfaces are ubiquitous and of a crucial role in determining functionality of biological systems and in enabling energy conversion applications. We study computationally such processes to understand structure-function relationships at the molecular level.

We will discuss studies in the following two primary fields: (1) Photovoltaic and charge transfer properties of organic semiconductors materials. (2) Charge transport through voltage-biased molecular scale bridges. Importantly we establish predictive computational scheme that addresses key challenges. Our studies are employed in conjunction with experimental efforts to design materials and applications that control and tune relevant physical properties