Research & Discoveries

The MONET team has collaborated on the publication of an ACS Cent Sci paper detailing a new structurally based representation system that is capable of handling the stochastic nature of polymers. The proposed system hopes to provide a more effective language for communication within the polymer community and increase cohesion between the researchers within the community.  Read more about the MONET Team's "BigSMILES: A Structurally-Based Line Notation for Describing Macromolecules" in the ACS… read more about MONET Team Paves the Way for Polymer Informatics »

Dr. Shangguo Hou of the Welsher lab has developed an adaptive real-time 3D single particle tracking method which can capture the binding events of single viruses to the surface of live cells. The microscope uses an adaptive algorithm which changes tracking parameters to adjust to changes in the motion of the virus particle. This method opens new avenues into probing the first contacts of virions with cells and tissue. Learn more about the new method in the most recent issue of Small, available here.   read more about Welsher Lab Opens New Avenues to Probe Contact of Virions with Cells and Tissue »

The labs of Professors Michael Therien and David Beratan have collaborated to engineer polarized excited states to "U-Turn" electron transfer. Their recent findings demonstrate that oppositely polarized electronically excited states can be employed to steer photoexcited states toward useful, high-energy products.  Read more about how their synthesis of a "supermolecule" allows more of the energy harvested from a photon and how this could be a game changing strategy for solar cells in their recent read more about Therien and Beratan Labs Get Excited About Solar Energy »

A team effort by the Derbyshire lab has led to the identification of human genes and pathways that facilitate the infection of liver cells by Plasmodium parasites, the causative agents of malaria. Their results suggest that this parasite co-opts the vesicular trafficking of its host cell to support its dramatic growth during the liver stage of infection. This work provides insights into the poorly understood interactions between Plasmodium parasites and the host liver cells they invade. Learn more about their… read more about Derbyshire Lab Takes Aim at Human Cell Machinery »

Knowledge of metal-trafficking processes can be leveraged to develop small molecules that help cells regain metal homeostasis for optimal cellular function or conversely that push cells away from homeostasis and into cellular distress. A recently published Viewpoint from Lizzie Hunsaker highlights lessons and opportunities for research in an area rich for therapeutic development at the interface of inorganic chemistry and cellular biology.  Read more in the Inorganic Chemistry article available… read more about Franz Lab Interfaces Inorganic Chemistry and Cellular Biology while Outside of Metal Comfort Zones »

A team led by Professors Jiyong Hong and Pei Zhou has discovered a small molecule drug that can stop cancer cells from becoming resistant to chemotherapy. The new compound, which was tested in an animal model of melanoma, could serve as a powerful adjuvant to make current chemotherapies more effective. It works by thwarting cancer’s ability to survive, evolve, and adapt to the onslaught of DNA damage wrought by traditional chemotherapy drugs like cisplatin.  Read more about their discovery in the June 6 edition of read more about Small Molecule Drug May Prevent Chemotherapy Resistance »

The Malcolmson lab has demonstrated that conjugated enynes undergo efficient and selective intermolecular 1,4-hydroamination to afford chiral allenes with a variety of primary and secondary aliphatic amines as well as benzophenone imine as an ammonia surrogate. A large number of allenes are obtained in racemic form with an achiral Pd(DPEPhos) catalyst. Through the design and development of a novel PHOX ligand, the group illustrates that highly enantioenriched allenes may be obtained in several cases. A perfluoroaryl… read more about Malcolmson Lab Illustrates Chiral Allene Synthesis by Pd-Catalyzed Amine–Enyne Couplings »

Lizzie Hunsaker of the Franz lab has discovered that modulating copper levels in the growth environment of Candida albicans reduces tolerance of this pathogen to widely prescribed azole antifungal drugs. Their results suggest that, even though these drugs are capable of coordinating transition metal centers, the observed copper-potentiated activity is not due to the formation of a copper complex. Instead, the data point to a broader relationship between Cu homeostasis and azole antifungals, a relationship that the lab… read more about Franz lab discovers relationship between copper levels and drug tolerance in fungal pathogen Candida albicans »

The Malcolmson lab has demonstrated that internal dienes may undergo regio- and enantioselective additions of enolate pronuclephiles. The transformations are promoted by Pd(PHOX) and Bronsted acid co-catalysts and deliver numerous products bearing 1,2-disubstituted olefins and a variety of alkyl groups at the stereogenic carbon. Read more about this research here in Chemical Science.   read more about Malcolmson Lab Develops Enantioselective Alkylations of Enolates with Dienes »

Rene Raphemot, Amber Eubanks, and other members of the Derbyshire lab, in collaboration with the Haystead lab in the Pharmacology department, have discovered the first reported inhibitors of an atypical Plasmodium kinase - PK9. Their results suggest that this protein kinase is important in ubiquitin signaling in the malaria parasite, and inhibition of this pathway leads to a unique growth of parasites during liver stage infection. These advancements lend insights into novel parasite biology. Read more in Cell… read more about Derbyshire Lab Discovers Chemical Probe that Reveals Malaria Parasite Signaling »

An international collaboration with the Beratan lab reports in Proceedings of the National Academy of Sciences that voltages may induce coherent long-range electron transport through biomolecules and other molecular structures. The authors describe a novel transport mechanism that supports electron flow across appreciable distances utilizing voltage-induced long-range electronic delocalization. This mechanism explains experiments that find a weak temperature dependence for long range electron… read more about Beratan Lab Using Voltage to Induce Coherent Long-Range Electron Transport »

The Roizen laboratory is developing a strategy to employ the intrinsic geometric constraints of a molecule to alter of the site of C-H functionalization reactions. Previously, they had demonstrated that sulfamate esters could be used to guide site-selective chlorine-transfer to a typically unreactive C–H bond. This was the first demonstration that sulfamate esters could guide exogenous atom-transfer processes.  Their research, published in the Journal of Organic Chemistry, builds on this concept,… read more about Roizen Lab Opens Door to Engaging Sulfamate Esters in Site-Selective Functionalization of Small Molecules »

The Malcolmson lab has recently shown that gem-difluoroazadienes can serve as a novel building block for the synthesis of chiral alpha-trifluoromethyl amines via the vicinal fluoro-functionalization of its alkene. Alpha-trifluoromethyl amines are important medicinal motifs as the CF3 group serves as a proteolysis-resistant surrogate for an amide. In this work, the research team has demonstrated that AgF addition across the azadiene is catalyzed by a phosphine, leading to a metastable alpha-CF3 azaallyl–silver… read more about Malcolmson Lab Demonstrates New Route to Alpha-Trifluoromethyl Amines »

The Hargrove Lab has created a general, high throughput technique for screening small molecule probes against different RNA targets using a fluorescence indicator displacement (FID) assay. Learn more about their fast and convenient method to simultaneously evaluate small molecule libraries against different RNA targets and classify them based on affinity and selectivity patterns in a recent Organic & Biomolecular Chemistry article here.    read more about Hargrove Lab Screens Against RNA Targets »

Agostino Migliore, Darius Teo and additional members of the Beratan Lab, with collaborators at USC, take an important step towards understanding intracellular redox signaling at the core of DNA repair and replication processes. Experiments suggesting a role for DNA charge transport in mediating such signaling have been the subject of a heated debated in recent literature. The lab has demonstrated that charge transfer between a [4Fe4S] protein and a nucleic acid duplex is unidirectional. This… read more about Unraveling Important Constraints on the Mechanisms for Redox Signaling in DNA Replication and Repair »

The static correlation error inherent in commonly used density functional approximations (DFAs) has seriously hindered the application of density functional theory (DFT) to strongly correlated systems. Here, an effective fractional-spin correction against the important issue of static/strong correlation in DFT is developed. With this, the flat-plane behavior of various DFAs is largely restored, and the potential energy curves of dissociation of ionic species, single bonds, and multiple bonds are properly described, which… read more about Yang Lab Describing Correlation with Fractional-spin Correction in DFT »

While the majority of small molecule chemical probes and drugs to date modulate the action of proteins, the Hargrove Lab is searching for small molecules that selectively engage binding pockets of RNA. In their most recent work, the group discovered the first ligands for the triple helix structure of an oncogenic long non-coding RNA MALAT1. The synthesis, evaluation and computational analysis of these novel small molecules revealed trends between small molecule shapes and their binding behavior. Together, these… read more about Hargrove Lab Searches for Small Molecules that Selectively Engage Binding Pockets of RNA »

The enantioselective and intermolecular addition of nucleophiles to internal olefins is a challenging process due to the typically low reactivity of these substrates. Hydroaminations of 1,4-disubstituted dienes present further challenges as several product regioisomers may be obtained and reactions tend to be reversible, leading to erosion of enantiopurity of products over time. The Malcolmson lab has now demonstrated that Pd–PHOX catalysts facilitate the regio- and enantioselective hydroamination of internal dienes with… read more about Malcolmson Lab Illustrates Enantioselective Hydroamination of Internal Dienes »

Non-coding RNAs have been identified that are essential for cellular regulation and that are misregulated in disease; however, the development of tools to study these RNAs has been challenging. To harness existing knowledge into the development of RNA-targeted chemical probes, the Hargrove lab examined the RNA targets, design and discovery strategies, and characterization techniques for ligands in the RNA-targeted BIoactive ligaNd Database (R-BIND).  Further, the survey… read more about Hargrove Lab Hopes to Expedite the Discovery of RNA-targeted Ligands »

GGTDTC, a copper prochelator of dithiocarbamate was developed to release dithiocarbamate (DTC) in cancer expressing gamma-glutamyl transferase enzyme. Upon release DTC is free to bind to Cu to form toxic Cu(DTC)2 . GGTDTC was found to selectively release diethyldithiocarbamate only in prostate cancer cells with measurable gamma-glutamyl transferase activity.  These findings underscore a new strategy to leverage the amplified copper metabolism of prostate cancer by conditional activation of a metal‐binding… read more about Franz Lab Combating Prostate Cancer One Metal at a Time »

The Charbonneau lab is bringing together researchers from industry and academia to develop a tool for automatizing protein crystal recognition.  Scientists came together to collect half a million images of protein crystallization experiments into a database that can specify which of these protein cocktails led to crystallization, based on human evaluation. The team then worked with a group led by Vincent Vanhoucke from Google Brain to apply the latest in artificial intelligence to help identify crystals in… read more about Charbonneau Lab Using A.I. to Recognize Crystals in Protein Crystallization Experiments »

Building upon their initial work illustrating the use of 2-azadienes for the enantioselective synthesis of challenging amine scaffolds, the Malcolmson lab has now reported that these reagents may engage in reductive couplings with imines for the synthesis of anti-1,2-diamines.  The Cu-catalyzed process is highly chemo-, diastereo-, and enantioselective for the preparation of a range of diamines, including those that have largely remained elusive until now.  The authors additionally highlight the… read more about Malcolmson Lab Demonstrates Reductive Coupling Strategy for 1,2-Diamine Synthesis »

The Derbyshire Lab is attempting to target the Malaria-causing parasite, Plasmodium, in the liver before it can reach the red blood cells.  In their recent PLOS Pathogen publication, available here, Derbyshire lab members use an inhibitor to curtail the parasite’s ability to reproduce inside the liver. Read more about their study in the Duke Today highlight!     read more about Derbyshire Lab Targets Malaria Parasite in the Liver »

The collaborative efforts of the Derbyshire and Haystead labs reveal that compounds that bind to Hsp90 represent a class of molecules that inhibit both blood- and liver-stage Plasmodium parasites. This dual-stage inhibition is ideal for antimalarials, and their work highlights the potential of Hsp90 inhibitors as drug partners in combination therapies.  Read more about this research in an April issue of Antimicrobial Agents and Chemotherapy article here.   read more about Derbyshire Lab Finds Hsp90 Inhibitors That May Aid in Treating Malaria »

The Franz Lab and collaborators explored the antibacterial mechanism of PcephPT, a prodrug of the antimicrobial chelator pyrithione.  Graduate students Jacqueline Zaengle-Barone and Abigail Jackson and former grad student David Besse found that PcephPT has an unconventional mode of action, requiring β-lactamase expression and copper availability for maximal activity. This “prochelator" overcomes the liability of metal chelation toxicity because it does not chelate metal ions until specifically… read more about Franz Lab Demonstrates Copper’s Role in Antibacterial Mechanism of a Prochelator »

A Departmental Collaboration is lighting up MRIs! Junu Bae of the Wang Lab and Zijian Zhou of the Warren Lab have developed chemical tags that attach to molecules, making them light up under MRI! Read more about these tags and how they could change how drugs target illness in the Wang/Warren lab article available in the March 9 publication of Science Advances.   read more about Wang and Warren Collaboration Report a Novel Hyperpolarization Tagging Strategy »

Professors David Beratan and Peng Zhang, with collaborators at NYU and ASU, have designed, built, and demonstrated current splitters and charge-transport junctions based on self-assembling nucleic acids. These constructs promise to expand the functionality of self-assembling bio-inspired electronic devices at the nanoscale. Learn more about their design from Arizona State's Biodesign Center for Bioelectronics & Biosensors or read more in the February 26 issue of Nature Nanotechnology!… read more about Charge Splitters and Charge Transport Junctions Based on Guanine Quadruplexes »

The Malcolmson lab has demonstrated that olefins may act as alkylating agents for the enantioselective intermolecular addition of enol-type nucleophiles under Pd catalysis. Typically, polarized electrophiles are required for couplings with enolates/enols or their equivalents, reducing atom economy and potentially functional group tolerance. In this work, Prof. Malcolmson, graduate student Nathan Adamson, and undergraduate Katie Wilbur show that activated pronucleophiles undergo enantioselective addition to a variety of… read more about Malcolmson Lab Illustrates Olefins as Alkylating Agents for Enantioselective Synthesis »

The high temperatures and intense UV irradiation of the early earth made DNA particularly susceptible to damage. Beratan’s group used theory, modeling, and simulation to explore the mechanism of photochemical repair of damaged DNA by the enzyme photolyases. The group focused on the critical (and much debated) photo-induced electron-transfer reaction that leads to DNA repair. The group resolved a long-standing debate on the role of adenine in the repair, and found that thermophilic and hyperthermophilic DNA photolyases… read more about Beratan Group Sheds Light on DNA Repair »