Chemistry Commons^™

Racemic And Enantiopure Forms Of 3‐Ethyl‐3‐Phenylpyrrolidin‐2‐One Adopt Very Different Crystal Structures, Arcadius V. Krivoshein, Sergey V. Lindeman, Tatiana V. Timofeeva, Victor N. Khrustalev

Chemistry Faculty Research and Publications

3‐Ethyl‐3‐phenylpyrrolidin‐2‐one (EPP) is an experimental anticonvulsant based on the newly proposed α‐substituted amide group pharmacophore. These compounds show robust activity in animal models of drug‐resistant epilepsy and are thus promising for clinical development. In order to understand pharmaceutically relevant properties of such compounds, we are conducting an extensive investigation of their structures in the solid state. In this article, we report chiral high‐performance liquid chromatography (HPLC) separation, determination of absolute configuration of enantiomers, and crystal structures of EPP. Preparative resolution of EPP enantiomers by chiral HPLC was accomplished on the Chiralcel OJ stationary phase in the polar‐organic mode. Using …

Altering The Coordination Of Iron Porphyrins By Ionic Liquid Nanodomains In Mixed Solvent Systems, Abderrahman Atifi, Michael D. Ryan

Chemistry Faculty Research and Publications

The solvent environment around iron porphyrin complexes was examined using mixed molecular/RTIL (room temperature ionic liquid) solutions. The formation of nanodomains in these solutions provides different solvation environments for substrates that could have significant impact on their chemical reactivity. Iron porphyrins (Fe(P)), whose properties are sensitive to solvent and ligation changes, were used to probe the molecular/RTIL environment. The addition of RTILs to molecular solvents shifted the redox potentials to more positive values. When there was no ligation change upon reduction, the shift in the E° values were correlated to the Gutmann acceptor number, as was observed for other …

When Substituents Do Not Matter: Frontier Orbitals Explain The Unusually High And Invariant Oxidation Potential In Alkoxy-, Alkyl-, And H-Substituted Iptycenes, Maxim V. Ivanov, Denan Wang, Shriya Wadumethrige, Rajendra Rathore

Chemistry Faculty Research and Publications

Frontier molecular orbitals (FMOs) have played a critical role in predicting reactivity/selectivity of pericyclic reactions. Here we show that the structurally similar iptycene-based hydroquinone ether (HE), that is, ^MeOIpt and ^BOHE/^BHHE, molecules have drastically different ordering of bisallylic and quinoidal FMOs. They are almost degenerate in ^BOHE/^BHHE, while in ^MeOIpt, the bisallylic orbital lies far below the quinoidal HOMO. Oxidation of ^BOHE/^BHHE induces coplanarization of the methoxy group and destabilizes the bisallylic HOMO, leading to a relatively low oxidation potential. In ^MeOIpt, considerable energy …

Bimetallic Cooperativity In Proton Reduction With An Amido‐Bridged Cobalt Catalyst, Kenneth K. Kpogo, Shivnath Mazumder, Denan Wang, H. Bernhard Schlegel, Adam T. Fiedler, Cláudio N. Verani

Chemistry Faculty Research and Publications

The bimetallic catalyst [Co^II₂(L¹)(bpy)₂]ClO₄ (1), in which L¹ is an [NN′₂O₂] fused ligand, efficiently reduced H⁺ to H₂ in CH₃CN in the presence of 100 equiv of HOAc with a turnover number of 18 and a Faradaic efficiency of 94 % after 3 h of bulk electrolysis at −1.6 V (vs. Ag/AgCl). This observation allowed the proposal that this bimetallic cooperativity is associated with distance, angle, and orbital alignment of the two Co centers, as promoted by the unique Co−N_{amido …}

Mqct. I. Inelastic Scattering Of Two Asymmetric-Top Rotors With Application To H2O + H2O, Alexander Semenov, Dmitri Babikov

Chemistry Faculty Research and Publications

A mixed quantum/classical theory (MQCT) for the inelastic collision of two asymmetric-top rotor molecules is developed. In this method, the quantum state-to-state transitions between the rotational states of molecules (internal) are treated quantum mechanically using the time-dependent Schrodinger equation, whereas their relative translational motion (responsible for scattering) is treated classically, using the average trajectory approach. Two versions of the formula for transition matrix elements are presented: a straightforward approach that uses numerical multidimensional quadrature over all the internal degrees of freedom and a more standard analytic approach that uses the expansion of the PES over the basis set of spherical …

Unraveling The Coulombic Forces In Electronically Decoupled Bichromophoric Systems During Two Successive Electron Transfers, Maxim V. Ivanov, Shriya Wadumethrige, Denan Wang, Rajendra Rathore

Chemistry Faculty Research and Publications

Coulombic forces are vital in modulating the electron transfer dynamics in both synthetic and biological polychromophoric assemblies, yet quantitative studies of the impact of such forces are rare, as it is difficult to disentangle electrostatic forces from simple electronic coupling. To address this problem, the impact of Coulombic interactions in the successive removal of two electrons from a model set of spirobifluorenes, where the interchromophoric electronic coupling is nonexistent, is quantitatively assessed. By systematically varying the separation of the bifluorene moieties using model compounds, ion pairing, and solvation, these interactions, with energies up to about 0.4 V, are absent at …

Reactivity Of (1-Methoxycarbonylpentadienyl)Iron(1+) Cations With Hydride, Methyl, And Nitrogen Nucleophiles, Yuzhi Ma, Young K. Yun, Julie L. Wondergem, Anobick Sar, Jayapal Reddy Gone, Sergey V. Lindeman, William A. Donaldson

Chemistry Faculty Research and Publications

The reaction of tricarbonyl and (dicarbonyl)triphenylphosphine (1-methoxycarbonyl-pentadientyl)iron(1+) cations 7 and 8 with methyl lithium, NaBH₃CN, or potassium phthalimide affords (pentenediyl)iron complexes 9a-c and 11a-b, while reaction with dimethylcuprate, gave (E,Z-diene)iron complexes 10 and 12. Oxidatively induced-reductive elimination of 9a-c gave vinylcyclopropanecarboxylates 17a-c. The optically active vinylcyclopropane (+)-17a, prepared from (1S)-7, undergoes olefin cross-metathesis with excess (+)-18 to yield (+)-19, a C9C16 synthon for the antifungal agent ambruticin. Alternatively reaction of 7 with methanesulfonamide or …

Toward Reliable Modeling Of S-Nitrosothiol Chemistry: Structure And Properties Of Methyl Thionitrite (Ch3sno), An S-Nitrosocysteine Model, Dmitry Khomyakov, Qadir K. Timerghazin

Chemistry Faculty Research and Publications

Methyl thionitrite CH₃SNO is an important model of S-nitrosated cysteine aminoacid residue (CysNO), a ubiquitous biological S-nitrosothiol (RSNO) involved in numerous physiological processes. As such, CH₃SNO can provide insights into the intrinsic properties of the —SNO group in CysNO, in particular, its weak and labile S—N bond. Here, we report an ab initio computational investigation of the structure and properties of CH₃SNO using a composite Feller-Peterson-Dixon scheme based on the explicitly correlated coupled cluster with single, double, and perturbative triple excitations calculations extrapolated to the complete basis set limit, CCSD(T)-F12/CBS, with a number of …

Analysis Of Ultrafast Transient Absorption Spectroscopy Data Using Integrative Data Analysis Platform: 1. Data Processing, Fitting, And Model Selection, Evgenii L. Kovrigin

Chemistry Faculty Research and Publications

This manuscript describes a workflow for analysis of transient absorption (TA) spectroscopy data using Integrative Data Analysis Platforms (IDAP) software package. Time-dependent spectral series are analyzed through evaluation of the isosbestic point and kinetics of excited state and ground-state bleach decays. Model fitting and selection based on Akaike's Information Criterion is discussed. As a practical example, we analyze excitation decays of a common protein label, Alexa Fluor 647.

Effect Of Facial Encumbrance On Excimer Formation And Charge Resonance Stabilization In Model Bichromophoric Assemblies, Brandon Uhler, Maxim V. Ivanov, Damian Kokkin, Neil Reilly, Rajendra Rathore, Scott A. Reid

Chemistry Faculty Research and Publications

Excimer formation and charge resonance stabilization in covalently linked bichromophoric systems with flexible spacers are important processes relevant to biochemistry and functional materials. Requiring a π-stacked cofacial arrangement of a pair of aromatic molecules at a van der Waals contact, the underlying geometrical reorganization that accompanies these events continues to be debated. Here we use a variety of methods including two-color resonant two-photon ionization spectroscopy (2CR2PI), ion yield measurements, hole-burning spectroscopy (HB), and laser-induced fluorescence (LIF) excitation and emission spectroscopy to compare the gas-phase spectroscopy and dynamics of the van der Waals dimers of fluorene, 9-methylfluorene (MF), and 9,9′-dimethylfluorene (F1). …

Resolving Three-State Ligand-Binding Mechanisms By Isothermal Titration Calorimetry: A Simulation Study, Evgenii L. Kovrigin

Chemistry Faculty Research and Publications

In this paper, I theoretically analyzed ITC profiles for three-state equilibria involving ligand binding coupled to isomerization or dimerization transitions. Simulations demonstrate that the mechanisms where the free or ligand-bound protein undergoes dimerization (such that the ligand cannot bind to or dissociate from the dimer) produce very distinctive titration profiles. In contrast, profiles of the pre-existing equilibrium or induced-fit models cannot be distinguished from a simple two-state process, requiring data from additional techniques to positively identify these mechanisms.

Serendipitous Discovery Of Light-Induced (In Situ) Formation Of An Azo-Bridged Dimeric Sulfonated Naphthol As A Potent Ptp1b Inhibito, Robert D. Bongard, Michael Lepley, Khushabu Thakur, Marat R. Talipov, Jaladhi Nayak, Rachel A. Jones Lipinski, Chris Bohl, Noreena Sweeney, Ramani Ramchandran, Rajendra Rathore, Daniel S. Sem

Chemistry Faculty Research and Publications

Background

Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors [sic] that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results.

Results

Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and …

Oxygen Activation By Mononuclear Mn, Co, And Ni Centers In Biology And Synthetic Complexes, Adam T. Fiedler, Anne A. Fischer

Chemistry Faculty Research and Publications

The active sites of metalloenzymes that catalyze O₂-dependent reactions generally contain iron or copper ions. However, several enzymes are capable of activating O₂ at manganese or nickel centers instead, and a handful of dioxygenases exhibit activity when substituted with cobalt. This minireview summarizes the catalytic properties of oxygenases and oxidases with mononuclear Mn, Co, or Ni active sites, including oxalate-degrading oxidases, catechol dioxygenases, and quercetin dioxygenase. In addition, recent developments in the O₂ reactivity of synthetic Mn, Co, or Ni complexes are described, with an emphasis on the nature of reactive intermediates featuring superoxo-, peroxo-, or …

Nmr Line Shape Analysis Of A Multi-State Ligand Binding Mechanism In Chitosanase, Shoko Shinya, Mariana G. Ghinet, Ryszard Brzezinski, Kyoko Furuita, Chojiro Kojima, Sneha Shah, Evgenii L. Kovrigin, Tamo Fukamizo

Chemistry Faculty Research and Publications

Chitosan interaction with chitosanase was examined through analysis of spectral line shapes in the NMR HSQC titration experiments. We established that the substrate, chitosan hexamer, binds to the enzyme through the three-state induced-fit mechanism with fast formation of the encounter complex followed by slow isomerization of the bound-state into the final conformation. Mapping of the chemical shift perturbations in two sequential steps of the mechanism highlighted involvement of the substrate-binding subsites and the hinge region in the binding reaction. Equilibrium parameters of the three-state model agreed with the overall thermodynamic dissociation constant determined by ITC. This study presented the first …

Isolation Of A Chiral Anthracene Cation Radical: X-Ray Crystallography And Computational Interrogation Of Its Racemization, Mikhail V. Ivanov, Khushabu Thakur, Anshul Bhatnagar, Rajendra Rathore

Chemistry Faculty Research and Publications

Chiral cation-radical salts hold significant promise as charge-transfer materials, chiroptical switches, and electron-transfer catalysts for enantioselective synthesis. Herein we demonstrate that the readily-available chiral 9,10-diphenyleanthracene derivative (i.e.^SANT) forms a robust cation radical, whose structure was elucidated by X-ray crystallography and DFT calculations. While ^SANT was observed to racemize on a timescale (t_1/2) of 1.1 hours, a computational conformational search and kinetic analysis of the racemization pathway led us to identify a simple methyl substituted ^SANT derivative, which does not racemize (racemization t_1/2 10¹³–10¹⁷ years).

Implicating The Contributions Of Surface And Bulk States On Carrier Trapping And Photocurrent Performance Of Bivo4 Photoanodes, Brian Pattengale, Jier Huang

Chemistry Faculty Research and Publications

Monoclinic-scheelite BiVO₄ has been widely studied as a promising oxygen evolution reaction (OER) catalyst in artificial photosynthesis. Though significant progress to improve or augment its catalysis performance has been made, fundamental understanding of its relatively poor performance as a bare material is lacking. In this paper, we report the correlation of the surface structure and trap states with charge separation efficiency and OER performance of bare BiVO₄ photoanodes viavarying the sample thickness. Using X-ray absorption spectroscopy (XAS), we observed a more compacted, symmetric Bi center in the surface state. Using transient absorption (TA) spectroscopy, we show that the …

Modeling Of S‐Nitrosothiol–Thiol Reactions Of Biological Significance: Hno Production By S‐Thiolation Requires A Proton Shuttle And Stabilization Of Polar Intermediates, Lena V. Ivanova, Daniel Cibich, Gregory Deye, Marat R. Talipov, Qadir K. Timerghazin

Chemistry Faculty Research and Publications

Nitroxyl (HNO), a reduced form of the important gasotransmitter nitric oxide, exhibits its own unique biological activity. A possible biological pathway of HNO formation is the S‐thiolation reaction between thiols and S‐nitrosothiols (RSNOs). Our density functional theory (DFT) calculations suggested that S‐thiolation proceeds through a proton transfer from the thiol to the RSNO nitrogen atom, which increases electrophilicity of the RSNO sulfur, followed by nucleophilic attack by thiol, yielding a charge‐separated zwitterionic intermediate structure RSS⁺(R)N(H)O⁻ (Zi), which decomposes to yield HNO and disulfide RSSR. In the gas phase, the proton transfer and the S−S …

Active Site Structures Of Cyp11a1 In The Presence Of Its Physiological Substrates And Alterations Upon Binding Of Adrenodoxin, Qianhong Zhu, Piotr J. Mak, Robert C. Tuckey, James R. Kincaid

Chemistry Faculty Research and Publications

The rate-limiting step in the steroid synthesis pathway is catalyzed by CYP11A1 through three sequential reactions. The first two steps involve hydroxylations at positions 22 and 20, generating 20(R),22(R)-dihydroxycholesterol (20R,22R-DiOHCH), with the third stage leading to a C20–C22 bond cleavage, forming pregnenolone. This work provides detailed information about the active site structure of CYP11A1 in the resting state and substrate-bound ferric forms as well as the CO-ligated adducts. In addition, high-quality resonance Raman spectra are reported for the dioxygen complexes, providing new insight into the status of Fe–O–O fragments encountered during the …

Biocompatible Copper Oxide Nanoparticle Composites From Cellulose And Chitosan: Facile Synthesis, Unique Structure, And Antimicrobial Activity, Chieu D. Tran, James Makuvaza, Erik Munson, Brian Bennett

Chemistry Faculty Research and Publications

Copper in various forms has been known to have bactericidal activity. Challenges to its application include preventing mobilization of the copper, to both extend activity and avoid toxicity, and bioincompatibility of many candidate substrates for copper immobilization. Using a simple ionic liquid, butylmethylimmidazolium chloride as the solvent, we developed a facile and green method to synthesize biocompatible composites containing copper oxide nanoparticles (CuONPs) from cellulose (CEL) and chitosan (CS) or CEL and keratin (KER). Spectroscopy and imaging results indicate that CEL, CS, and KER remained chemically intact and were homogeneously distributed in the composites with CuONPs with size of 22 …

Cytoprotective Activated Protein C Averts Nlrp3 Inflammasome–Induced Ischemia-Reperfusion Injury Via Mtorc1 Inhibition, Sumra Nazir, Ihsan Gadi, Moh'd Mohanad Al-Dabet, Ahmed Elwakiel, Shrey Kohli, Sanchita Ghosh, Jayakumar Manoharan, Satish Ranjan, Fabian Bock, Ruediger C. Braun-Dullaeus, Charles T. Esmon, Tobias B. Huber, Eric Camerer, Chris Dockendorff, John H. Griffin, Berend Isermann, Khurrum Shahzad

Chemistry Faculty Research and Publications

Cytoprotection by activated protein C (aPC) after ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation, and hence, cell-death forms disjunct from immunologically silent apoptosis are, in theory, more likely to be relevant. Because pyroptosis (ie, cell death resulting from inflammasome activation) is typically observed in IRI, we speculated that aPC ameliorates IRI by inhibiting inflammasome activation. Here we analyzed the impact of aPC on inflammasome activity in myocardial and renal IRIs. aPC treatment before or after myocardial IRI reduced infarct size and Nlrp3 inflammasome activation in mice. Kinetic in vivo analyses revealed that Nlrp3 …

Three Sources Of Errors In The Ehrenfest Treatment Of Inelastic Scattering And Possible Ways Of Resolving Them, Alexander Semenov, Dmitri Babikov

Chemistry Faculty Research and Publications

In order to identify the origin of possible errors in the mixed quantum/classical approach to inelastic scattering [A. Semenov and D. Babikov, J. Chem. Phys. 140, 044306 (2014) and A. Semenov, M.-L. Dubernet, and D. Babikov, J. Chem. Phys. 141, 114304 (2014)], a simplified model is considered that consists of one intermolecular degree of freedom and two intramolecular states, coupled by a simple potential. For this system, analytic derivations are carried out to determine (i) the exact quantum mechanical solution of the inelastic scattering problem, (ii) a simplified version of it with all oscillatory terms neglected, and (iii) …

Redox And Spectroscopic Properties Of Iron Porphyrin Nitroxyl In The Presence Of Weak Acids, Md. Hafizur Rahman, Michael D. Ryan

Chemistry Faculty Research and Publications

The spectroelectrochemistry and voltammetry of Fe(OEP) (NO) in the presence of substituted phenols was studied. Cyclic voltammetry showed that two closely spaced waves were observed for the reduction of Fe(OEP) (NO) in the presence of substituted phenols. The first wave was a single electron reduction under voltammetric conditions. The second wave was kinetically controlled, multielectron process. Visible spectroelectrochemistry of Fe(OEP) (NO) in the presence of substituted phenols showed that three species were present during the electrolysis. Additional spectroscopic studies indicated that the two reduction species were Fe(OEP) (HNO) and Fe(OEP)(H₂NOH). The Fe(OEP) (HNO) species, which can be generated …

Cofacially Arrayed Polyfluorenes: Spontaneous Formation Of Π-Stacked Assemblies In The Gas Phase, Maxim Vadimovich Ivanov, Neil Reilly, Brandon Uhler, Damian Kokkin, Rajendra Rathore, Scott A. Reid

Chemistry Faculty Research and Publications

Understanding geometrical and size dependencies of through-space charge delocalization in multichromophoric systems is critical to model electron transfer and transport in materials and biomolecules. In this work, we examine the size evolution of hole delocalization in van der Waals clusters of fluorene (i.e., (F)_n), where a range of geometries are possible, reflecting both π-stacking and C–H/π interactions. Using mass-selected two-color resonant two-photon ionization spectroscopy (2CR2PI), we measure electronic spectra and vertical ionization potentials (IPs) in the gas phase. Results are compared with model covalently linked assemblies (denoted Fn), exhibiting a sterically enforced cofacial (i.e., …

Recombination Reactions As A Possible Mechanism Of Mass-Independent Fractionation Of Sulfur Isotopes In The Archean Atmosphere Of Earth, Dmitri Babikov

Chemistry Faculty Research and Publications

A hierarchy of isotopically substituted recombination reactions is formulated for production of sulfur allotropes in the anoxic atmosphere of Archean Earth. The corresponding system of kinetics equations is solved analytically to obtain concise expressions for isotopic enrichments, with focus on mass-independent isotope effects due to symmetry, ignoring smaller mass-dependent effects. Proper inclusion of atom-exchange processes is shown to be important. This model predicts significant and equal depletions driven by reaction stoichiometry for all rare isotopes: ³³S, ³⁴S, and ³⁶S. Interestingly, the ratio of capital Δ values obtained within this model for ³³S and ³⁶S is …

Light-Driven Hydrogen Production From Aqueous Solutions Based On A New Dubois-Type Nickel Catalyst, Y. Zhou, S. Yang, J. Huang

Chemistry Faculty Research and Publications

In this work, we report a new photocatalytic system that links multifunctional semiconductor nanocrystals with emerging water-soluble molecular catalysts made of earth-abundant elements for H₂ generation [Ni(P₂^RN₂^R′)₂(BF₄)₂]⁴⁻, R = Ph, R′ = [PhSO₃]⁻ (NiS). This noble metal free hybrid exhibits remarkable catalytic activity with a turnover number of 511 for H₂ production and a photon-to-H₂ conversion efficiency of 12.5%. The mechanistic insight into such high efficiency in this photocatalytic system was examined using a combination of steady-state emission and time-resolved …

The Effect Of Mo Doping On The Charge Separation Dynamics And Photocurrent Performance Of Bivo4 Photoanodes, Brian Pattengale, Jier Huang

Chemistry Faculty Research and Publications

Doping with electron-rich elements in BiVO₄ photoanodes has been demonstrated as a desirable approach for improving their carrier mobility and charge separation efficiency. However, the effect of doping and dopant concentration on the carrier dynamics and photoelectrochemical performance remains unclear. In this work, we examined the effects of Mo doping on the charge separation dynamics and photocurrent performance in BiVO₄photoanodes. We show that the photocurrent of BiVO₄ photoanodes increases with increasing concentration of the Mo dopant, which can be attributed to both the improved carrier mobility resulting from increased electron density and charge separation efficiency due …

Dihedral-Angle-Controlled Crossover From Static Hole Delocalization To Dynamic Hopping In Biaryl Cation Radicals, Marat R. Talipov, Tushar S. Navale, Mohammad M. Hossain, Ruchi Shukla, Maxim V. Ivanov, Rajendra Rathore

Chemistry Faculty Research and Publications

In cases of coherent charge-transfer mechanism in biaryl compounds the rates follow a squared cosine trend with varying dihedral angle. Herein we demonstrate using a series of biaryl cation radicals with varying dihedral angles that the hole stabilization shows two different regimes where the mechanism of the hole stabilization switches over from (static) delocalization over both aryl rings to (dynamic) hopping. The experimental data and DFT calculations of biaryls with different dihedral angles unequivocally support that a crossover from delocalization to hopping occurs at a unique dihedral angle where the electronic coupling (H_ab) is one half of …

Synthesis, X-Ray Structures, Electronic Properties, And O2/No Reactivities Of Thiol Dioxygenase Active-Site Models, Anne A. Fischer, Nuru Stracey, Sergey V. Lindeman, Thomas C. Brunold, Adam T. Fiedler

Chemistry Faculty Research and Publications

Mononuclear non-heme iron complexes that serve as structural and functional mimics of the thiol dioxygenases (TDOs), cysteine dioxygenase (CDO) and cysteamine dioxygenase (ADO), have been prepared and characterized with crystallographic, spectroscopic, kinetic, and computational methods. The high-spin Fe(II) complexes feature the facially coordinating tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (^Ph2TIP) ligand that replicates the three histidine (3His) triad of the TDO active sites. Further coordination with bidentate l-cysteine ethyl ester (CysOEt) or cysteamine (CysAm) anions yielded five-coordinate (5C) complexes that resemble the substrate-bound forms of CDO and ADO, respectively. Detailed electronic-structure descriptions of the [Fe(^Ph2TIP)(L_S,N)]BPh₄ complexes, where L …

Critical Role Of The Secondary Binding Pocket In Modulating The Enzymatic Activity Of Dusp5 Toward Phosphorylated Erks, Marat R. Talipov, Jaladhi Nayak, Michael Lepley, Robert D. Bongard, Daniel Sem, Ramani Ramchandran, Rajendra Rathore

Chemistry Faculty Research and Publications

DUSP5 is an inducible nuclear dual-specificity phosphatase that specifically interacts with and deactivates extracellular signal-regulated kinases ERK1 and ERK2, which are responsible for cell proliferation, differentiation, and survival. The phosphatase domain (PD) of DUSP5 has unique structural features absent from other nuclear DUSPs, such as the presence of a secondary anion-binding site in the proximity of the reaction center and a glutamic acid E264 positioned next to the catalytic cysteine C263, as well as a remote intramolecular disulfide linkage. The overall 400 ns molecular dynamics simulations indicate that the secondary binding site of DUSP5 PD acts as an allosteric regulator …

Conformational States Of Cytochrome P450 Oxidoreductase Evaluated By Förster Resonance Energy Transfer Using Ultrafast Transient Absorption Spectroscopy, Elizaveta A. Kovrigina, Brian Pattengale, Chuanwu Xia, Azamat R. Galiakhmetov, Jier Huang, Jung Ja Kim, Evgenii L. Kovrigin

Chemistry Faculty Research and Publications

NADPH-cytochrome P450 oxidoreductase (CYPOR) was shown to undergo large conformational rearrangements in its functional cycle. Using a new Förster resonance energy transfer (FRET) approach based on femtosecond transient absorption spectroscopy (TA), we determined the donor–acceptor distance distribution in the reduced and oxidized states of CYPOR. The unmatched time resolution of TA allowed the quantitative assessment of the donor–acceptor FRET, indicating that CYPOR assumes a closed conformation in both reduced and oxidized states in the absence of the redox partner. The described ultrafast TA measurements of FRET with readily available red–infrared fluorescent labels open new opportunities for structural studies in chromophore-rich …