A former doctoral student from the Grewer laboratory, Dr. Laura Zielewicz (now at Pfizer) has published her work on a novel prodrug inhibitor approach to block glutamate release through reverse transport in ACS Chemical Neuroscience. She developed several aspartate derivatives, which were shown to be effective in preventing potassium-induced glutamate efflux, when binding to the intracellular substrate recognition site of the transporters under pathophysiological conditions encountered during a stroke. At the same time, glutamate uptake was not impaired, when ion concentrations were in the normal, physiological range. This method could have wide-ranging applications for studying glutamate-induced neuronal cell death.
Publication link: https://pubs.acs.org/doi/10.1021/acschemneuro.3c00651
Professor Besson, graduate student Christopher Hossack and collaborator Prof. Cahill from the George Washington University give an overview of their recent work about f-element chemistry in a Frontier article published in Dalton Transactions. They show how the use of the new class of ligand developed by the Besson group allows the synthesis of a range of lanthanoid complexes with unique structural, optical and magnetic properties. The authors also comment on the future opportunities (and challenges!) opened by those results, including applications in the retreatment of nuclear fuel and the creation of novel multifunctional materials combining attractive optical and magnetic properties.
Publication Link: https://pubs.rsc.org/en/content/articlelanding/2023/DT/D3DT02737F
Dimitrov group has published an Account “Copper-Based Nanomaterials for Fine-Pitch Interconnects in Microelectronics”. In this Account, the authors present a novel approach employing self-supported nanoporous copper (np-Cu) films for low-temperature joint formation in electronic packaging. The key innovation lies in the incorporation of tin (Sn) into the np-Cu structure, which enables joint formation at significantly reduced sintering temperatures. The main goal is to create intermetallic compound (IMC)-based connections between two Cu substrates. This incorporation of Sn is achieved through an all-electrochemical bottom-up process, involving the conformal deposition of a thin Sn layer onto finely structured np-Cu, initially formed through the dealloying of copper-zinc (Cu-Zn) alloys.
This Account not only delves into state-of-the-art technologies that employ nanostructured films as materials for interconnections but also highlights optimization studies for the Sn-coating processes. The coating process is executed through a carefully calibrated galvanic pulse plating technique, designed to preserve the structural porosity. This meticulous fine-tuning guarantees an optimal Cu/Sn atomic ratio, facilitating the formation of the desired precursor bonding intermetallic compound (IMC), Cu6Sn5. Furthermore, this study explores the potential applicability of the synthesized Cu-Sn IMC nanomaterial for enabling low-temperature joint formation. This is done via sintering, conducted at temperatures ranging from 300°C down to 200°C under 20 MPa pressure in a forming gas atmosphere. In conclusion, a cross-sectional examination of the formed joints reveals robust densified bonds with minimal porosity, primarily composed of the ultimately targeted Cu3Sn IMC.
Publication Link: https://pubs.acs.org/doi/epdf/10.1021/acs.accounts.3c00023
Yang Dong from the Grewer laboratory published her discovery of a conserved allosteric inhibition mechanism in glutamate/neutral amino acid transporters from the solute carrier 1 (SLC1) family in eLife. Her work not only demonstrated the existence and location of the allosteric binding site at the subunit interface of neutral amino acid transporters ASCT1 and 2, but also identified a novel allosteric inhibitor, with a structure unrelated to previous glutamate transporter inhibitors. This research, which was performed in collaboration with the Schlessinger laboratory at Mount Sinai School of Medicine, extends previous work of the Grewer/Schlessinger groups on competitive inhibitors, for the first time characterizing an allosteric inhibitor for ASCTs.
Conserved allosteric inhibition mechanism in SLC1 transporters. Dong Y, Wang J, Garibsingh RA, Hutchinson K, Shi Y, Eisenberg G, Yu X, Schlessinger A, Grewer C.Elife. 2023 Mar 1;12:e83464. doi: 10.7554/eLife.83464.
Research Paper from the Vallee and Solmaz Groups provides mechanistic insights into how mutations of the protein BicD2 cause devastating brain and muscle development diseases in infants
Mutations in the human protein BicD2 have been found to cause a subset of cases of
spinal muscular atrophy, which is the most common genetic cause of death in infants,
and other devastating brain and muscle developmental defects in infants. BicD2 facilitates
several transport pathways in the cell that are important for brain and muscle development,
however it is not clear how the human disease mutations result in the associated diseases.
A new collaborative paper from the research groups of Dr. Sozanne Solmaz, Associate Professor in our Chemistry Department, and Richard Vallee from the Department of Pathology, Columbia University Irving Medical Center, New York sheds insights into underlying disease causes of these human BicD2 mutations.
They examined the effects of known BicD2 mutations using in vitro biochemical and in vivo electroporation-mediated brain developmental assays. They found a clear relationship between the ability of BicD2 to bind to two distinct target proteins in controlling two distinct associated brain development processes that are active in brain progenitor cells or postmitotic neurons, respectively. Several of the disease mutations change the affinity towards these two target proteins in a distinct manner, resulting in preferential binding to one of the two target proteins and preferential activation of the associated brain developmental pathway. Errors in these brain developmental processes likely contribute to the specific human brain malformations associated with these BicD2 mutations.
Yi, J, Zhao X, Noell CR, Helmer P, Solmaz SR*, Vallee RB*. Role of Nesprin-2 and RanBP2 in BICD2-associated brain developmental disorders. PLoS Genet. 2023,19:e1010642.
Available from: 0.1371/journal.pgen.1010642
A publication from Fang Group, “Improvement of Oxygen Reduction Performance in Alkaline Media by Tuning Phase Structure of Pd-Bi Nanocatalysts (10.1021/jacs.1c08644)”, has been acknowledged by the Editor-in-Chief of JACS as one of the most cited papers from 2020 to 2021. Congratulations!
J. Am. Chem. Soc. 2021, 143, 38, 15891–15897
Rozners group has published a paper “Triplex-Forming Peptide Nucleic Acid Controls Dynamic Conformations of RNA Bulges” in Journal of the American Chemical Society. This study demonstrates the ability to control the dynamic equilibria of RNA’s structure, which is important for studying structure–function relationships in RNA biology and may have potential in novel therapeutic approaches targeting disease-related RNAs.
Ryan, C. A.; Rahman, M. M.; Kumar, V.; Rozners, E. Triplex-Forming Peptide Nucleic Acid Controls Dynamic Conformations of RNA Bulges. J. Am. Chem. Soc. 2023, 145, 10497–10504.
Read more here
The Fang lab at Binghamton University, in collaboration with researchers from Cornell University, has recently published a study in ACS Energy Letters. This paper highlights a unique class of spinel nanocatalysts composed of shape-controlled CoMn2O4 nanocrystals. Compared to other Co- and Mn-based spinels, notably, the CoMn2O4 nano-octahedra exhibited unmatched electrocatalytic activity for oxygen reduction in alkaline media to date. Read more here ACS Energy Lett. 2023, 8, 8, 3631–3638
The Solmaz lab (Binghamton University) has published a collaborative paper with the Wang lab (Rensselaer Polytechnic Institute) and the Trybus lab (University of Vermont) in the prestigious journal eLIFE. In the paper, a cargo-recognition alpha-helix was identified in the protein Nup358, which is required for activation of a transport pathway that is essential for brain development. Read more here.
The Hirschi Lab
The Hirschi lab (Binghamton University) and the Arnold lab (Cal Tech) were recently featured by Ben List in SynFacts for their biocatalytic study involving 'Enzymatic Nitrene Insertion into C-H Bonds for the Synthesis of Enantioenriched Amides.'
The article was originally featured as a "Hot Paper" in Angewandte Chem. Int. Ed.
The Fang group successfully synthesized two types of Pd-Bi nanocrystals with different crystal structures, known as monoclinic phase and fcc phase. They further identified that the monoclinic phase exhibits superior catalytic activity for alkaline oxygen reduction reaction, one of the significant reactions in the fuel cell system. This discovery has been published in J. Am. Chem. Soc.
Ming Zhou, Jiangna Guo, Bo Zhao, Can Li, Lihua Zhang and Jiye Fang, J. Am. Chem. Soc. 2021, 143, 38, 15891–15897.
Publication Link: Journal of the American Chemical Society
Working together with collaborators, Fang group recently published a research article, “Synthesis of Core@Shell Cu-Ni@Pt-Cu Nano-Octahedra and Their Improved MOR Activity” in Angewandte Chemie, one of the prime chemistry journals in the world (2019 Impact Factor: 12.959). This work demonstrated a colloidal seed‐mediated approach to prepare octahedral CuNi@Pt‐Cu core@shell nanocrystals using CuNi octahedral cores as the template. By precisely controlling the synthesis conditions, uniform Pt‐based thin-shells can be achieved. The resultant carbon‐supported CuNi@Pt‐Cu core@shell nano‐octahedra showed superior activity in electrochemical methanol oxidation reaction (MOR), indicating that both the lattice strain and shape effects play a key role in this catalyst improvement.
Publication Link: doi.org
WileyChem Link: WileyChem
Eriks Rozners and Venubabu Kotikam have published an Account “Amide-Modified RNA: Using Protein Backbone to Modulate Function of Short Interfering RNAs”. Remarkably, this major chemical modification has unexpectedly little effect on structure and stability of the RNA duplex and, at certain positions of short interfering RNAs, eliminates some of the undesired off-target activity while improving their on-target activity. The article was chosen by Editors as the Cover Image of the September 2020 issue of Accounts of Chemical Research.
Read more here: https://pubs.acs.org/doi/10.1021/acs.accounts.0c00249
Dimitrov and Fang Groups
Dimitrov and Fang groups together with a Cornell research team recently published
their development of fraction-controlled Pt-Cu-based porous film electrocatalysts
used for alkaline oxygen reduction reaction (ORR) in ACS Catal. The catalysts prepared
using an electrochemical deposition-stripping synthetic approach show superb electrocatalytic
ORR activity in 0.1M KOH with control of the introduced Au composition. After a composition
optimization, the de-alloyed Pt37Cu56Au7 ternary catalyst exhibits a 7.2-fold higher
mass activity than that of the standard Pt/C and the longest durability among all
tested samples including the Pt/C.
“Enhanced ORR Kinetics on Au-Doped Pt-Cu Porous Films in Alkaline Media”, Yunxiang Xie, Yao Yang, David A. Muller, Hector D. Abruna, Nikolay Dimitrov, and Jiye Fang, ACS Catal., 10 (xx) 9967 - 9976, (2020).
Bane and Tumey groups
The Bane group (Chemistry) and Tumey group (Pharmaceutical Sciences) recently reported on an expanded repertoire of substrates that can be recognized by the microbial transglutaminase (mTG) enzyme. Applications of mTG utilizing the noncanonical substrates are demonstrated in providing isopeptide diversity and enabling side-chain hydrazide derivatization on peptides and proteins. Together, the work shines light on hitherto undiscovered capabilities of mTG and further broadens the versatility of this enzyme in biotechnology. This publication is the second full-length paper generated from the partnership between the Bane and Tumey groups.
T. I. Chio, B. R. Demestichas, B. M. Brems, S. L. Bane, L. N. Tumey, Expanding the Versatility of Microbial Transglutaminase Using α-Effect Nucleophiles as Noncanonical Substrates. Angew. Chem. Int. Ed. 2020, 59, 13814-13820. doi: 10.1002/anie.202001830
Read more here
The Dimitrov group reported on the development and application of all-electrochemically synthesized nanoporous (np) Au-Cu-Pt alloy thin film as catalysts for formic acid oxidation (FAO) reaction. The work emphasizes a pursuit of most efficient catalytic routes for the production of clean energy like by smart materials design at atomic level, involving controlled alloy electrodeposition followed by oxidative copper removal. The unique advantage of the best performing np Au-Cu-(2.6%)Pt catalyst is associated with its exclusive selectivity in support of the preferred direct FAO mechanism along with unseen long-lasting no-passivation behavior in the course of wide-potential-range cycling tests.
Ultralow Pt-loading Nanoporous Au-Cu-Pt Thin Film as Highly Active and Durable Catalyst for Formic Acid Oxidation, Yunxiang Xie and Nikolay Dimitrov, Applied Catalysis B: Environmental, 2019, October 31 (https://doi.org/10.1016/j.apcatb.2019.118366) [Epub ahead of print].
Read more here.
A collaborative work from the Qiang group and the Vugmeyster group at CU Denver has been published on PNAS. This work solved the very first molecular structure of a post-translational modified beta-amyloid fibril. This site-specific modification, with the phosphorylation at residue S8 on Abeta sequence, induces the formation of a more-ordered N-terminal fibril structure with more thermodynamic stable core. In addition, this modification leads to rapid cross-seeded fibrillation to the wild-type Abeta, which may accelerate the pathological amyloid deposition.
This work has been posted as a University Research News headline on the Office of Science homepage at https://www.energy.gov/science/office-science , and reported in the PNAS news
Read more here.
The Panetier group, in collaboration with the Jurss group at the University of Mississippi, reported a joint experimental and computational study on the use of three novel cobalt catalysts for electrochemical CO2 reduction in aqueous solutions. This study shows that as the rigidity of the macrocycle is increased, selectivity and activity for CO2 reduction over the competing hydrogen evolution reaction is enhanced. As such the most rigid catalyst performs CO2 reduction in water with an overpotential of 420 mV and a Faradaic yield of 93%.
X. Su, K.M. McCardle, L. Chen, J.A. Panetier and J.W. Jurss, Robust and Selective
Cobalt Catalysts Bearing Redox-Active Bipyridyl-N-heterocyclic Carbene Frameworks
for Electrochemical CO2 Reduction in Aqueous Solutions, ACS Catal. 2019, 9, 7398−7408Chem
Biol. 2019 May 6. doi: 10.1021/acschembio.9b00194 [Epub ahead
Read more here.
Laura Zielewicz from the Grewer laboratory published her research on the mechanism of inhibition of glutamate transporters in ACS Chemical Biology. This work shows that binding of negatively-charged inhibitors occurs within the transmembrane electric field, resulting in voltage dependence of inhibitor binding and dissociation. This finding is important for our understanding of how glutamate interacts with the transporter at the excitatory synapse in the mammalian brain.
Transient Kinetics Reveal Mechanism and Voltage Dependence of Inhibitor and Substrate Binding to Glutamate Transporters. Zielewicz L, Wang J, Ndaru E, Grewer CT ACS Chem Biol. 2019 May 6. doi: 10.1021/acschembio.9b00194 [Epub ahead of print].
Read more here.
The Panetier group, in collaboration with researchers from Texas A&M University and DePaul University, reported a joint experimental and computational study on the use of imidazolium-functionalized manganese tricarbonyl bipyridine complexes for CO2reduction. This study, which was published in JACS, suggests that imidazolium groups in the secondary coordination sphere promote the formation of a local hydration shell that facilitates the protonation of CO2 reduction intermediates.
S. Sung, X. Li, L.M. Wolf, J.R. Meeder, N.S. Bhuvanesh, K.A. Grice, J.A. Panetier, and M. Nippe, Synergistic Effects of Imidazolium-Functionalization on fac-Mn(CO)3 Bipyridine Catalyst Platforms for Electrocatalytic Carbon Dioxide Reduction, J. Am. Chem. Soc. 2019, 141, 6569-6582.
Read more here.
In collaboration with colleagues from University of Rochester and Elizabethtown College, Rozners group has published a paper “Synthetic, Structural, and RNA Binding Studies on 2-Aminopyridine-Modified Triplex-Forming Peptide Nucleic Acids” in Chemistry: A European Journal. The study was designated as Very Important Paper by the reviewers and featured as a Cover Picture of the March 21 issue of Chemistry: A European Journal.
Kotikam, V., Kennedy, S. D., MacKay, J. A., and Rozners, E. Synthetic, Structural, and RNA Binding Studies on 2-Aminopyridine-Modified Triplex-Forming Peptide Nucleic Acids. Chem. Eur. J. 2019, 25,4367- 4372.
Read more here.
Elias Ndaru published work on the synthesis and characterization of novel inhibitors of alanine cysteine serine transporter ASCT2, in collaboration with the laboratory of Dr. Avner Schlessinger from Mount Sinai School of Medicine. Amino acid derivatives with sulfonic acid ester and sulfonamide linkages were identified as ASCT2 inhibitors with the most potent compound displaying an affinity in the low microM range.
Novel alanine serine cysteine transporter 2 (ASCT2) inhibitors based on sulfonamide and sulfonic acid ester scaffolds. Ndaru E, Garibsingh RA, Shi Y, Wallace E, Zakrepine P, Wang J, Schlessinger A, Grewer C. J Gen Physiol., 2019 Feb 4 epub ahead of print.
Read more here.
Qiang & An Groups
A collaborative work from the Qiang and An groups has recently been published on PNAS. This work describes the studies of thermodynamic intermediate states of interactions between pH-Low insertion (pHLIP) peptides and membrane bilayers, using advanced solid-state NMR spectroscopy. A multi-stage pH-modulated membrane insertion model for pHLIP peptides was proposed. Graduate and undergraduate students S. Otieno, S. Hanz, B. Chakravorty from the Qiang group, and graduate students A. Zhang and L. Klees from the An group contributed to this work.
S.A. Otieno, S.Z. Hanz, B. Chakravorty, A. Zhang, L.M. Klees, M. An, and W. Qiang, pH-dependent thermodynamic intermediates of pHLIP membrane insertion determined by solid-state NMR spectroscopy. Proc. Natl. Acad. Sci. U.S.A., 2018, 115(48), 12194-12199.
Read more here.
The Fang group, in collaboration with researchers from Cornell and NTU, recently reported their observation of phase transitions of formamidinium lead iodide (FAPbI3) under pressure. The article was just accepted by J. Am. Chem. Soc. FAPbI3 is a hybrid compound, consisting of a perovskite alpha-phase and hexagonal (non-perovskite) delta-phase. Study on the pressure-induced structural evolution of this organic-inorganic compound is a hot topic. For the first time, the authors determined that the pressure could accelerate the alpha- to delta-FAPbI3 transformation.
Shaojie Jiang, Yiliang Luan, Joon I. Jang, Tom Baikie, Xin Huang, Ruipeng Li, Felix O. Saouma, Zhongwu Wang, Timothy J. White and Jiye Fang, Phase Transitions of Formamidinium Lead Iodide Perovskite under Pressure, J. Am. Chem. Soc., 2018, 140(42), 13952-13957.
Read more here.
The honor thesis research of an undergraduate student Vladislav Roytman is the subject of a recent publication in Chem. Eur. J. from the Vetticatt group at Binghamton University. This paper details the use of 13C kinetic isotope effects and DFT calculations as a novel probe to distinguish between of enol and enamine mechanisms in aminocatalysis.
Roytman, V. A.; Karugu, R. W.; Hong, Y.; Hirschi, J. S.; Vetticatt, M. J. 13C Kinetic Isotope Effects as a Quantitative Probe To Distinguish between Enol and Enamine Mechanisms in Aminocatalysis Chem. Eur. J. 2018, 24(32), 8098-8102.
Read more here.