Medicinal-Pharmaceutical Chemistry Commons^™

Peroxiredoxin Catalysis At Atomic Resolution, Arden Perkins, Derek Parsonage, Kimberly J. Nelson, O. Maduka Ogba, Paul Ha-Yeon Cheong, Leslie B. Poole, P. Andrew Karplus

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidases that guard cells against oxidative damage, are virulence factors for pathogens, and are involved in eukaryotic redox regulatory pathways. We have analyzed catalytically active crystals to capture atomic resolution snapshots of a PrxQ-subfamily enzyme (from Xanthomonas campestris) proceeding through thiolate, sulfenate, and sulfinate species. These analyses provide structures of unprecedented accuracy for seeding theoretical studies, and show novel conformational intermediates giving insight into the reaction pathway. Based on a highly non-standard geometry seen for the sulfenate intermediate, we infer that the sulfenate formation itself can strongly promote local unfolding of the active site to …

Ruthenium-Catalyzed Amination Of Secondary Alcohols Using Borrowing Hydrogen Methodology, Kostiantyn O. Marichev, James M. Takacs

Chemistry Department: Faculty Publications

A new ruthenium complex catalyzes the amination of primary and secondary alcohols and the regioselective mono- and sequential diamination of diols via the borrowing hydrogen pathway. Several variations on new intra- and intermolecular cyclizations of aminoalcohols, diols and diamines lead to heterocyclic ring systems.

Αβ-Peptide Mimics Of Z-Domain Peptides, Samuel H. Gellman, James W. Checco

Chemistry Department: Faculty Publications

Described are αβ-peptide mimics of Z-domain scaffold pep tides, methods of making them, and methods of using them. The αβ-peptide mimics include B-amino acid residues and, optionally, disulfide bonds to stabilize the conformation of the mimics. The compounds may be truncated as compared to conventional Z-domain scaffold peptides and are resistant to proteolytic degradation due to the presence off-amino acid residues. The mimics can be made so as to bind selectively to a desired target.

Engineering Escherichia Coli For High‑Yield Geraniol Production With Biotransformation Of Geranyl Acetate To Geraniol Under Fed‑Batch Culture, Wei Liu, Xin Xu, Rubing Zhang, Tao Cheng, Yujin Cao, Xiaoxiao Li, Jiantao Guo, Huizhou Liu, Mo Xian

Chemistry Department: Faculty Publications

Background: Geraniol is an acyclic monoterpene alcohol, which exhibits good prospect as a gasoline alternative. Geraniol is naturally encountered in plants at low concentrations and an attractive target for microbial engineering. Geraniol has been heterologously produced in Escherichia coli, but the low titer hinders its industrial applications. Moreover, bioconversion of geraniol by E. coli remains largely unknown.

Results: Recombinant overexpression of Ocimum basilicum geraniol synthase, Abies grandis geranyl diphosphate synthase, and a heterotic mevalonate pathway in E. coli BL21 (DE3) enabled the production of up to 68.6 ± 3 mg/L geraniol in shake flasks. Initial fed-batch fermentation only increased geraniol …

Ring Closures And The Hammond Postulate, Charles A. Kingsbury

Chemistry Department: Faculty Publications

This work reports an investigation of ring closure processes in relation to the Hammond postulate. Calculations favor the importance of thermodynamics, not kinetics, as the basis for the Hammond postulate. A kinetically rapid, but thermodynamically unfavorable reaction is shown to resemble product. The ease of ring closure to three-membered rings, compared to four-membered rings, is thought to be associated with conformational mobility and perhaps vibrations coupled to the reaction coordinate motion in the case of four-membered rings.

Highly Porous Zirconium Metal−Organic Frameworks With Β‑Uh3‑Like Topology Based On Elongated Tetrahedral Linkers, Xin Zhang, Xu Zhang, Jacob A. Johnson, Yu-Sheng Chen, Jian Zhang

Chemistry Department: Faculty Publications

Two non-interpenetrated zirconium metal−organic frameworks (Zr-MOFs), NPF-200 and NPF-201, were synthesized via the assembly of elongated tetrahedral linkers with Zr₆ and Zr₈ clusters. They represent the first examples of MOFs to have the β-UH₃-like, 4,12,12T1 topology. Upon activation, NPF-200 exhibits the largest BET surface area (5463 m²g⁻¹) and void volume (81.6%) among all MOFs formed from tetrahedral ligands. Composed of negative-charged boron-centered tetrahedral linkers, NPF-201 is an anionic Zr-MOF which selectively uptakes photoactive [Ru(bpy)₃]²⁺for heterogeneous photo-oxidation of thioanisole.

Additional supporting information files are attached below.

Flexble Robotic Actuators, Aaron D. Mazzeo, Stephen A. Morin, Robert F. Shepherd, George M. Whitesides, William B. Kalb

Chemistry Department: Faculty Publications

Some embodiments of the disclosed subject matter includes a laminated robotic actuator. The laminated robotic actuator includes a strain-limiting layer comprising a flexible, non extensible material in the form of a sheet or thin film, a flexible inflatable layer in the form of a thin film or sheet in facing relationship with the Strain-limiting layer, wherein the inflatable layer is selectively adhered to the strain-limiting layer, and wherein a portion of an un-adhered region between the strain-limiting layer and the inflatable layer defines a pressurizable channel, and at least one fluid inlet in fluid communication with the pressurizable channel. The …

Hlarp7 C-Terminal Domain Contains An Xrrm That Binds The 3' Hairpin Of 7sk Rna, Catherine D. Eichhorn, Rahul Chug, Juli Feigon

Chemistry Department: Faculty Publications

The 7SK small nuclear ribonucleoprotein (snRNP) sequesters and inactivates the positive transcription elongation factor b (P-TEFb), an essential eukaryotic mRNA transcription factor. The human La-related protein group 7 (hLARP7) is a constitutive component of the 7SK snRNP and localizes to the 3' terminus of the 7SK long noncoding RNA. hLARP7, and in particular its C-terminal domain (CTD), is essential for 7SK RNA stability and assembly with P-TEFb. The hLARP7 N-terminal Lamodule binds and protects the 3' end from degradation, but the structural and functional role of its CTD is unclear.We report the solution NMR structure of the hLARP7 CTD and …

Processes And Reagents For Making Daryliodonium Salts, Stephen Dimagno

Chemistry Department: Faculty Publications

This invention relates to processes and reagents for making diaryliodonium salts, which are useful for the preparation of fluorinated and radiofluorinated aromatic compounds.

Close Encounters With Creative Chemical Thinking: An Outreach Presentation Using Movie Clips About The Elemental Composition Of Aliens And Extraterrestrial Minerals, Mark A. Griep, Marjorie L. Mikasen

Chemistry Department: Faculty Publications

To introduce more chemistry into a middle and high school bioengineering camp experience, we developed an educational and entertaining presentation that examines the chemistry in movies about aliens and minerals from outer space. Our goal was to help the campers to think creatively about the bioengineering projects they are doing and about its chemistry. After watching each movie clip, we explain whether the chemistry in the clip is real or fake, and then describe the real chemistry that inspired it. The chemical touchstone for the presentation is the periodic table. First, the campers learn that aliens in five movies are …

Signature Of Coexistence Of Superconductivity And Ferromagnetism In Two-Dimensional Nbse2 Triggered By Surface Molecular Adsorption, Xiaojiao Zhu, Yuqiao Guo, Hao Cheng, Jun Dai, Xingda An, Jiyin Zhao, Kangzhen Tian, Shiqiang Wei, Xiao Cheng Zeng, Changzheng Wu, Yi Xie

Chemistry Department: Faculty Publications

Ferromagnetism is usually deemed incompatible with superconductivity. Consequently, the coexistence of superconductivity and ferromagnetism is usually observed only in elegantly designed multi-ingredient structures in which the two competing electronic states originate from separate structural components. Here we report the use of surface molecular adsorption to induce ferromagnetism in two-dimensional superconducting NbSe₂, representing the freestanding case of the coexistence of superconductivity and ferromagnetism in one two-dimensional nanomaterial. Surface-structural modulation of the ultrathin superconducting NbSe₂ by polar reductive hydrazine molecules triggers a slight elongation of the covalent Nb–Se bond, which weakens the covalent interaction and enhances the ionicity of …

Analytic Ab Initio-Based Molecular Interaction Potential For The Bro·H2O Complex, Ross D. Hoehn, Sachin D. Yeole, Sabre Kais, Joseph S. Francisco

Chemistry Department: Faculty Publications

Radical halogen oxide species play important roles within atmospheric processes, specifically those responsible for the removal of O3. To facilitate future investigations on this family of compounds, RCCSD(T)/aug-cc-pVQZ-level electronic structure calculations were employed to generate individual-molecule optimized geometries, as well as to determine the global minimum energy structure for the BrO·H₂O complex. This information facilitated the generation of several one-dimensional potential energy surface (PES) scans for the BrO·H₂O complex. Scans were performed for both the ground state and the first excited state; this inclusion is due to a low-lying first electronic excited-state energy. These rigid-geometry PES …

Live, Attenuated Vaccines And Methods Of Making And Using, Jiantao Guo, Qingsheng Li, Wei Niu, Yue Li, Nanxi Wang

Chemistry Department: Faculty Publications

A live, attenuated HIV vaccine is provided, and methods of making a atenuated HIV vaccine are provided.