UCLA

Organic Colloquium - Prof. Vincent N. G. Lindsay
2022-03-31 16:00 (America/Los_Angeles)
Stereoselective Synthesis and Applications of Sulfonylcyclopropanols as Modular Cyclopropanone and Homoenolate Equivalents

Chem 218 Student Exit Seminar: Gail Vinnacombe
2022-03-31 12:00
“Surface Functionalization, Patterning, and in Situ Growth of Gold Nanoparticles”

The 2022 Cabot Microelectronics Corp. Lecture
2022-03-30 16:00
A new era in solar energy conversion and optoelectronics enabled by the humble halide perovskites?

Chem 278: Prof. Karsten Meyer
2022-03-29 16:00
“Super-Oxidized” Iron Nitrido/Imido and “Super-Reduced” Iron Nitrosyl Complexes in tris-Carbene Coordination Spheres – and how Iron Really Feels About it

Chem 228: Prof. Thuc-Quyen Nguyen
2022-03-28 16:00
“Understanding Unconventional Doping Mechanisms in Organic Semiconductors”

Special Organic Colloquium - Prof. Joshua G. Pierce
2022-03-24 16:00
Complex Molecule Synthesis at the Interface of Biology: Adventures in Medicinal Chemistry and Chemical Biology

Chem 218 Student Exit Seminar: Yiyi Yao
2022-03-17 12:00
“Structural Stability and Phase Transformation Behavior in Nanostructured Energy Storage Materials”

Chem 278: Prof. Kimberly A. See
2022-03-16 16:15
“One is the Loneliest Number: Multivalent and Multielectron Processes for Next-Generation Batteries”

Catalysis Lectureship 2022 - Christophe Copéret, ETH Zürich
2022-03-16 14:30
Bridging the gap between well-defined and industrial catalysts via a molecular approach
Industrial processes, in particular large-scale ones, mostly rely on heterogeneous catalysts. The search for more sustainable processes and the changes in environmental policies impose the continuous development of improved catalyst performances and catalytic processes, as well as the exploration of alternative routes. However, due to their inherent complexity, heterogeneous catalysts are mostly developed empirically rather than through detailed structure – activity relationships as the nature of the active sites are rarely known.
In this context, our group has been interested in understanding and controlling chemistry on surfaces, with the ultimate goal to generate isolated metal sites with defined chemical environment.[1] This approach has been used to develop highly active and selective single-site catalysts that can overperformed their homogeneous counterparts, but it can also provide useful information to understand and further develop industrial catalysts[2] or to study much more complex systems such as supported nanoparticles, where support effects, interfaces, alloying… remain complex to understand at the molecular level.
This lecture will be developed around these themes and will show that a careful characterization of surface sites on a molecular level is key to develop high performance catalysts and to bridge the gap between fundamental and applied catalysis.[3]
References:
1 C. Copéret, A. Comas-Vives, M. P. Conley, D. Estes, A. Fedorov, V. Mougel, H. Nagae, F. Núñez-Zarur, P. A. Zhizhko Surface Organometallic and Coordination Chemistry towards Single-Site Heterogeneous Catalysts: Strategies, Methods, Structures, and Activities. Chem. Rev. 2016, 16, 323-421. DOI: 10.1021/acs.chemrev.5b00373
2 C. Copéret, F. Allouche, K. W. Chan, M. P. Conley, M. F. Delley, A. Fedorov, I. B. Moroz, V. Mougel, M. Pucino, K. Searles, K. Yamamoto, P. A. Zhizhko, Bridging the Gap between Industrial and Well-Defined Supported Catalysts. Angew. Chem. Int. Ed. 2018, 57, 6398-6440. DOI: 10.1002/anie.201702387
3 a) C. Copéret Single-Sites and Nanoparticles at Tailored Interfaces Prepared via Surface Organometallic Chemistry from Thermolytic Molecular Precursors. Acc. Chem. Res. 2019, 52, 1697-1708. DOI: 10.1021/acs.accounts.9b001388. b) Deciphering Metal-Oxide and Metal-Metal Interplay via Surface Organometallic Chemistry: A Case Study with CO2 Hydrogenation to Methanol. S. R. Docherty, C. Copéret J. Am. Chem. Soc. 2021, 143, 6767–6780. DOI: 10.1021/jacs.1c02555. c) Heterogeneous Alkane Dehydrogenation Catalysts Investigated via a Surface Organometallic Chemistry Approach. S. R. Docherty, L. Rochlitz, P.-A. Payard, C. Copéret Chem. Soc. Rev. 2021, 50, 5806 – 5822. DOI: 10.1039/d0cs01424a.

NSF Center for Integrated Catalysis Webinar Series
2022-03-15 12:30
“Towards understanding the role of mass transport in electrocatalysis: the role of dimensionless analysis and multi-scale modeling”

Chem 268 - John E. (Jack) Johnson
2022-03-11 15:30
“Biophysical Studies of an RNA Virus particle and its Maturation: Insights into an Elegantly Programmed Nano-machine”

Special Organic Colloquium - Prof. Herman O. Sintim
2022-03-10 16:00
Novel chemotypes of kinase inhibitors for the potential treatment of recurrent cancers
Abstract: Therapeutic resistance remains a critical issue in cancer treatment. While cancer patients who harbor dysregulated protein kinases benefit from the use of kinase inhibitors (KIs), many fail therapy and almost all patients become resistant to treatment, indicating a critical unmet need to prevent treatment failure.
Thus far (as of December 2021), the FDA has approved 69 protein kinase inhibitors and several others are also in various stages of clinical trials. Although many compounds that inhibit protein kinases have been described in the literature, only a small region of the chemical space has been explored for protein kinase inhibition and the majority of FDA approved kinase inhibitors contain only a handful of core moieties, such as indazole, quinoline, isoquinoline, quinazoline, pyrazole and pyrimidine. To belabor this point, about ~20% of FDA-approved protein kinases contain the pyrimidine moiety while six drugs contain quinazoline and eight drugs contain pyrazole. In other words, about 50% of approved protein kinase inhibitors contain one of pyrimidine, pyrazole or quinazoline, highlighting the lack of progress in using other regions of the chemical space to drug protein kinases. The Sintim group, integrating computational and experimental workflows, has identified a few novel chemotypes that inhibit disease-associated protein kinases (such as FLT3, RET, CDKs, Haspin) with sub-nanomolar IC50 values. Some of these new KI are long residence time (hours) inhibitors and have shown impressive efficacies in animal models of various cancers. Two of such compounds are currently undergoing toxicology studies to determine safe dosing regimens for potential phase 1 clinical trials against drug-resistant FLT3 (F691L and D835V/Y)-driven AML and RET (solvent front mutations)-driven lung cancers

Chem 218: Student Exit Seminar
2022-03-10 12:00
“Choosing the right lens: Energy surfaces and chemical identity in the photodissociation of Na2+ in different solvent environments”

Chem 278: Prof. James McCusker
2022-03-09 16:00
“Ultrafast Synthesis: Leveraging Time-resolved Spectroscopy for Targeted Synthetic Control of Ultrafast Dynamics in Transition Metal-based Chromophores”
Abstract: The interconversion of light and chemical energy is one of the most fundamental processes on Earth. Research on solar energy conversion, for example – which will ultimately lead to the next generation of solar energy technologies – has sought to replicate Nature’s solution through the realization of artificial constructs that mimic various aspects of photosynthesis. Whether it is the creation of potential gradients to generate current (i.e., photovoltaics) or more recent efforts coupling photo-generated electrons and holes to catalysts (e.g., photoredox catalysis), the critical first step is the absorption of light and the subsequent separation of charge. Transition metal-based chromophores are particularly well-suited for use in such schemes by virtue of the charge-transfer excited-states that a majority of them possess. Indeed, tremendous advances have been made through use of compounds such as [Ru(bpy)3]2+ and Ir(ppy)3 in areas ranging from solar energy conversion to photoredox catalysis. Despite the obvious advantages of ruthenium- and iridium-based chromophores, the fact that these elements are among the rarest in the earth’s crust raises legitimate questions concerning cost and scalability of processes reliant on such chromophores. Such issues, coupled with the possibility of unlocking new chemistry, has motivated exploring the possibility of replacing these compounds with chromophores based on earth-abundant first-row transition metals that can carry out analogous excited-state reaction chemistry. With these opportunities come significant challenges due to inherent differences in the electronic structures of first- versus second- and third-row metal complexes that profoundly impact the ability of such compounds to engage in the desired chemistry. The focus of our research program is therefore to understand the factors that determine the dynamics associated with charge-transfer excited-states of first-row transition metal-based chromophores, with the ultimate goal of circumventing and/or redefining their intrinsic photophysics in order to make feasible their use in a variety of light-driven applications. This seminar will outline the key scientific issues defining this challenge as well as discuss recent examples from our lab illustrating how these challenges can be met and, ultimately, overcome.

Chem 228: Stephen Quake
2022-03-07 16:00
“The Cell is a Bag of RNA”

Chem 248 - Organic Chemistry Student Seminar
2022-03-07 15:00
Recent Advancements in the Employment of Pd/Ni Catalyzed C-N Amide Cross-Coupling

Postponed - Chem 218: Student Exit Seminar - Samuel Lilak
2022-03-03 12:00

Organic Colloquium - Prof. Ross Denton
2022-03-03 12:00
“Phosphorus-Oriented” Method Development and Total Synthesis
Abstract: The lecture will describe the design, development and applications of new synthetic methods based upon phosphorus(V) reagents and catalysts. Topics will include catalytic halogenation, hydroxyl activation and the total synthesis of polychlorinated and trimeric phenol-derived natural products.

2022 M. Frederick Hawthorne Lecture
2022-03-02 16:00
“Releasing, or capturing, that is the question. Porous molecular materials”
Porous materials are one important class where the shape and distribution of “empty” space throughout the framework is a main determinant for the resulting functionality. For instance, zeolites are available with many different pore size and geometries, which is the fundament of their wide spread use in industry, e.g. as absorbents and catalysts. Drug delivery applications with porous inorganic materials are in the focus of several investigations all over the world. Following supramolecular principles, i.e., incorporating dynamically covalent bonds into a silica framework, we have reported a “break on-demand” of the silica structure. Recently we have developed disulfide-bridged organosilica nanoparticles with cage-like morphology, and assessed in detail their bioaccumulation in vivo.[1] Interestingly their lung accumulation and their ability to escape macrophage filtering open new promises for their use as drug delivery systems.
In addition they are able to stabilize out of equilibrium species and transport them inside cells were they can be released and evolve towards the equilibrium state.[2] But controlling the shape and the “emptiness”, of porous systems can allow the capture, and not release, of specific molecules, biomarkers. In particular a novel class of fluorescent artificial receptors (FAR) is introduced that can bind the neurotransmitters serotonin and dopamine in a bio-relevant concentration range with unprecedented affinity and selectivity.[3] The fully synthetic receptors are based on zeolites and rapid responding and thus enable instantaneous neurotransmitter detection through cost economic and facile absorbance- and emission-based assays. Their potential for high-throughput diagnostics in urine and for monitoring of important enzymatic reactions is shown.
Finally amongst the most studied porous systems in medicine are hydrogels, which are inherently more disordered porous system than the aforementioned inorganic host materials. An example of hybrid injectable hydrogels will be given for the treatment of fistula.[4]
References
[1] P. Picchetti et al. ACS Nano 2021, 15, 9701–9716
[2] P. Picchetti, L. De Cola et al. J. Am. Chem. Soc. 2021, 143, 7681-7687.
[3] F. Biedermann, L. De Cola et al. Adv. Mater. 2021, 33, 2104614.
[4] E. Piantanida, Materials Today Bio, 2021, 10, 100109

Special Organic Colloquium - Prof. Stuart Conway
2022-03-01 16:00
“The development and targeting of epigenetic drugs for therapeutic benefit”
Abstract: The talk will comprise two interconnected parts describing the development and targeting of epigenetic drugs for the treatment of disease.
The development of bromodomain ligands for the treatment of disease: bromodomains, protein modules that ‘read’ of lysine acetylation state, have emerged as important therapeutic targets for indications including oncology. I will describe our work on the design and synthesis of inhibitors for the BET and CREBBP/EP300 bromodomains, their biological effects, and their role as leads for cancer drug discovery. While the function of some human bromodomain-containing proteins (BCPs) has been heavily investigated, little is known about the role of these proteins in other species. I will describe work to identify 22 BCPs in Schistosoma mansoni (schistosomiasis/bilharzia). We have annotated one of these proteins as SmBRD3, in analogy to human BRD3, a member of the BET bromodomain family. I will discuss the design, synthesis, and validation of high affinity ligands for SmBRD3 and the use of these ligands in phenotypic studies on S. mansoni.
Targeting and imaging tumour hypoxia: Tumor hypoxia (low oxygen) is associated with therapy resistance and poor patient prognosis. Hypoxia-activated prodrugs, which target oxygen-deficient cells, represent a promising treatment strategy. We have demonstrated the pre-clinical efficacy of NI-Pano, a novel hypoxia-activated pro-drug of the clinically used lysine deacetylase inhibitor, panobinostat. NI-Pano is stable in normoxic (21% oxygen) conditions and undergoes NADPH-CYP-mediated enzymatic bioreduction to release panobinostat in hypoxia (<0.1% oxygen). NI-Pano exhibited growth delay effects as a single agent in mouse tumor xenografts. Pharmacokinetic analysis confirmed the presence of panobinostat in hypoxic mouse xenografts, but not in circulating plasma or kidneys. Our preclinical results provide a strong mechanistic rationale for the clinical development of NI-Pano for selective targeting of hypoxic tumors. Work to develop complementary imaging agents for hypoxia will also be discussed.

NSF Center for Integrated Catalysis Webinar Series
2022-03-01 13:00
“2D Particle Surfactants and Pickering Emulsions for Reagent Compartmentalization”

Chem 228: Prof. Denis Usvyat
2022-03-01 11:00
“High-accuracy Theoretical Treatment of Defects in Periodic Systems”

Chem 228: Robijn Bruinsma
2022-02-28 16:00
“Physics and the HIV-1 virus”

Chem 248 - Organic Chemistry Student Seminar
2022-02-28 15:00
Harnessing Bifunctional Ligands for Regioselective C–H Bond Functionalization

Chem 268 - Hung Ton-That
2022-02-25 15:30
“Sortase-catalyzed surface assembly in monoderm bacteria”

Insight-Driven Strategies in Catalysis for Selective Functionalizations
2022-02-24 16:00
Abstract: Detailed understanding of catalytic transformations is key to designing better catalysts and overcome pertinent challenges in synthesis. This talk will give insights on case studies and reactivity designs recently undertaken in our laboratory. The focus will be on multinuclear metal catalysis for the chemoselective and modular construction of molecules, the exploration of organogermanes in catalysis, and the development of synthetic strategies towards novel fluorinated motifs. Experimental and computational tools were applied in these studies.

Chem 278: Prof. Sara Skrabalak - MilliporeSigma Inorganic Nano-Materials Lecture
2022-02-23 16:00
“Multimetallic Nanomaterials by Design”

Chemistry at the Biomedicine Interface: Synthesis and Catalysis
2022-02-22 10:30
Abstract: Chemical reactivity can be utilized in many ways, including to improve synthetic access to new molecules and to devise tools to advance biomedicine. ‘Synthesis and catalysis’ are two themes interwoven throughout this presentation, which describes 1) the development of short synthetic routes to (–)-picrotoxinin, (–)-picrotin, and 5-methyl-picrotoxinin enabled by a late-stage strong-bond activation strategy for the long term goal of interrogating GABAa receptor combinatorial diversity, 2) the development of three methods for alkene hydrofunctionalization using Mn- and Co- hydrogen atom transfer chemistry, and 3) two studies in catalysis centered on one-carbon metabolism which improve understanding of how one-carbon metabolites contribute to health and disease.

Chem 268 - Jennifer Niven Shepherd
2022-02-18 15:30
“Characterization of RquA – a novel enzyme used in microbial rhodoquinone biosynthesis”

Searching for Selective Catalytic Reactions in Complex Molecular Environments
2022-02-17 16:00
Abstract: This lecture will describe recent developments in our efforts to develop catalysts for asymmetric reactions, in particular for the preparation of densely functionalized, stereochemically complex structures. Over time, our foci have been on enantioselectivity, site-selectivity and chemoselectivity. In much of our current work, we are studying issues of enantioselectivity as a prelude to the extrapolation of catalysis concepts to more complex molecular settings where multiple issues are presented in a singular substrate. Mechanistic paradigms, and their associated ambiguities – especially in light of catalyst or substrate conformational dynamics – will figure strongly in the lecture, raising analogies to enzymes. Finally, several interesting – and often unexpected – collaborations with colleagues in industry will be discussed.
