56 results on '"Babak Borhan"'
Search Results
2. A chiroptical approach for the absolute stereochemical determination of P-stereogenic centers
- Author
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Leo A. Joyce, Hadi Gholami, James E. Jackson, Debarshi Chakraborty, Aritra Sarkar, and Babak Borhan
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Axial chirality ,Stereochemistry ,Phosphorus oxide ,Chemistry ,media_common.quotation_subject ,Molecule ,General Chemistry ,Asymmetry ,media_common ,Stereocenter - Abstract
A simple chiroptical solution for the absolute stereochemical determination for asymmetric phosphorus V stereocenters is presented. Strong coordination of the phosphorus oxide with the Zn-metallo center of the racemic host Zn-MAPOL 2 leads to an induced axial chirality of the host, yielding a strong ECCD signal. A mnemonic is proposed to correlate the asymmetry of the guest molecule with the observed ECCD signal.
- Published
- 2021
3. Ritter-enabled catalytic asymmetric chloroamidation of olefins†
- Author
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Aritra Sarkar, Cecilia C Morgenstern, Richard J. Staples, Bardia Soltanzadeh, Babak Borhan, and Daniel C Steigerwald
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chemistry.chemical_classification ,General Chemistry ,Electrophilic aromatic substitution ,Combinatorial chemistry ,Sulfonamide ,Catalysis ,chemistry.chemical_compound ,Chemistry ,Nucleophile ,chemistry ,Reagent ,Enantiomeric excess ,Guanidine ,Alkyl - Abstract
Intermolecular asymmetric haloamination reactions are challenging due to the inherently high halenium affinity (HalA) of the nitrogen atom, which often leads to N-halogenated products as a kinetic trap. To circumvent this issue, acetonitrile, possessing a low HalA, was used as the nucleophile in the catalytic asymmetric Ritter-type chloroamidation of allyl-amides. This method is compatible with Z and E alkenes with both alkyl and aromatic substitution. Mild acidic workup reveals the 1,2-chloroamide products with enantiomeric excess greater than 95% for many examples. We also report the successful use of the sulfonamide chlorenium reagent dichloramine-T in this chlorenium-initiated catalytic asymmetric Ritter-type reaction. Facile modifications lead to chiral imidazoline, guanidine, and orthogonally protected 1,2,3 chiral tri-amines., Intermolecular haloamination reactions are challenging due to the high halenium affinity of the nitrogen atom. This is circumvented by using acetonitrile as an attenuated nucleophile, resulting in an enantioselective halo-Ritter reaction.
- Published
- 2020
4. Mechanistic Insights into the Origin of Stereoselectivity in an Asymmetric Chlorolactonization Catalyzed by (DHQD)2PHAL
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Kumar Dilip Ashtekar, Daniel Holmes, Babak Borhan, Aritra Sarkar, James E. Jackson, Paul Reed, Tayeb Kakeshpour, Daniel C. Whitehead, and Roozbeh Yousefi
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chemistry.chemical_classification ,Olefin fiber ,Substrate (chemistry) ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,0104 chemical sciences ,Colloid and Surface Chemistry ,chemistry ,Nucleophile ,Computational chemistry ,Electrophile ,Stereoselectivity ,Selectivity ,Lactone - Abstract
Electrophilic halofunctionalization reactions have undergone a resurgence sparked by recent discoveries in the field of catalytic asymmetric halocyclizations. To build mechanistic understanding of these asymmetric transformations, a toolbox of analytical methods has been deployed, addressing the roles of catalyst, electrophile (halenium donor), and nucleophile in determining rates and stereopreferences. The test reaction, (DHQD)2PHAL-catalyzed chlorocyclization of 4-arylpent-4-enoic acid with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH), is revealed to be first order in catalyst and chlorenium ion donor and zero order in alkenoic acid substrate under synthetically relevant conditions. The simplest interpretation is that rapid substrate-catalyst binding precedes rate-limiting chlorenium attack, controlling the face selectivity of both chlorine attack and lactone closure. ROESY and DFT studies, aided by crystal structures of carboxylic acids bound by the catalyst, point to a plausible resting state of the catalyst-substrate complex predisposed for asymmetric chlorolactonization. As revealed by our earlier labeling studies, these findings suggest modes of binding in the (DHQD)2PHAL chiral pocket that explain the system's remarkable control over rate- and enantioselection-determining events. Though a comprehensive modeling analysis is beyond the scope of the present work, quantum chemical analysis of the fragments' interactions and candidate reaction paths point to a one-step concerted process, with the nucleophile playing a critical role in activating the olefin for concomitant electrophilic attack.
- Published
- 2020
5. General strategy for tuning the Stokes shifts of near infrared cyanine dyes
- Author
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Wei-Tao Peng, Babak Borhan, Benjamin G. Levine, Mehdi Moemeni, Jun Zhang, Fangchun Liang, Chenchen Yang, and Richard R. Lunt
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Conformational change ,Materials science ,Substituent ,General Chemistry ,chemistry.chemical_compound ,symbols.namesake ,chemistry ,Chemical physics ,Stokes shift ,Materials Chemistry ,symbols ,Molecule ,Amine gas treating ,Cyanine ,Conformational isomerism ,Excitation - Abstract
We report a significant Stokes shift enhancement in near-infrared fluorescing cyanines as a result of C4′-substitution with cyclic or acyclic amines. Based on a combined experimental and density functional study, a simple strategy for optimizing the Stokes shift is proposed. By tuning the relative energies of cyanine-like and bis-dipolar conformers, differing in the rotational angle of the amine substituent, it is possible to develop molecules that undergo conformational change upon excitation, resulting in a predictable Stokes shift.
- Published
- 2020
6. A Mechanistically Inspired Halenium Ion Initiated Spiroketalization: Entry to Mono- and Dibromospiroketals
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Kumar Dilip Ashtekar, Hadi Gholami, Mehdi Moemeni, Ankush Chakraborty, Lindsey Kiiskila, Xinliang Ding, Edmond Toma, Christopher Rahn, and Babak Borhan
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Ions ,Molecular Structure ,Spiro Compounds ,Stereoisomerism ,General Medicine ,General Chemistry ,Bromine ,Furans ,Catalysis ,Article - Abstract
Employing halenium affinity (HalA) as a guiding tool, the weak nucleophilic character of alkyl ketones was modulated by the templating effect of a tethered 2-tetrahydropyranyl(THP)-protected alcohol towards realizing a bromenium ion initiated spiroketalization cascade. Addition of ethanol aided an early termination of the cascade by scavenging the THP group after the halofunctionalization stage, furnishing monobromospiroketals. Alternatively, exclusion of ethanol from the reaction mixture biased the transient oxocarbenium towards α-deprotonation that precedes a second bromofunctionalization event thus, furnishing dibrominated spiroketals. The regio- and stereoselectivity exploited in the current methodology provides a novel and rapid access to the dibrominated spiroketal motifs exhibited by several natural products.
- Published
- 2021
7. Control of Protonated Schiff Base Excited State Decay within Visual Protein Mimics: A Unified Model for Retinal Chromophores
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Margherita Maiuri, Ivan Rivalta, James H. Geiger, Tetyana Berbasova, Giulio Cerullo, Baptiste Demoulin, Marco Garavelli, Babak Borhan, Demoulin B., Maiuri M., Berbasova T., Geiger J.H., Borhan B., Garavelli M., Cerullo G., and Rivalta I.
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Rhodopsin ,Photochemistry ,Static Electricity ,Molecular Dynamics Simulation ,Catalysis ,chemistry.chemical_compound ,Ultrafast laser spectroscopy ,ultrafast optical spectroscopy ,excited state dynamic ,rhodopsin mimic ,Spectroscopy ,QM/MM method ,retinal Schiff base ,Schiff Bases ,Physics::Biological Physics ,Quantitative Biology::Biomolecules ,biology ,Organic Chemistry ,Retinal ,General Chemistry ,Chromophore ,Fluorescence ,chemistry ,Chemical physics ,Excited state ,biology.protein ,Visible spectrum - Abstract
Artificial biomimetic chromophore-protein complexes inspired by natural visual pigments can feature color tunability across the full visible spectrum. However, control of excited state dynamics of the retinal chromophore, which is of paramount importance for technological applications, is lacking due to its complex and subtle photophysics/photochemistry. Here, ultrafast transient absorption spectroscopy and quantum mechanics/molecular mechanics simulations are combined for the study of highly tunable rhodopsin mimics, as compared to retinal chromophores in solution. Conical intersections and transient fluorescent intermediates are identified with atomistic resolution, providing unambiguous assignment of their ultrafast excited state absorption features. The results point out that the electrostatic environment of the chromophore, modified by protein point mutations, affects its excited state properties allowing control of its photophysics with same power of chemical modifications of the chromophore. The complex nature of such fine control is a fundamental knowledge for the design of bio-mimetic opto-electronic and photonic devices.
- Published
- 2021
8. Zirconium-catalyzed asymmetric Kabachnik-Fields reactions of aromatic and aliphatic aldehydes
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Yijing Dai, William D. Wulff, Debarshi Chakraborty, Babak Borhan, and Li Zheng
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Zirconium ,Ligand ,Aryl ,chemistry.chemical_element ,General Chemistry ,Catalysis ,chemistry.chemical_compound ,Chemistry ,Aniline ,chemistry ,Yield (chemistry) ,Organic chemistry ,Amine gas treating ,Benzoic acid - Abstract
An effective catalyst has been developed for the three-component reaction of aldehydes, anilines and phosphites in an asymmetric catalytic Kabachnik–Fields reaction to give α-aminophosphonates. A catalyst was sought that would give high asymmetric inductions for aromatic and, and more particularly, for aliphatic aldehydes since there has not previously been an effective catalyst developed for this class of aldehydes. The optimal catalyst is prepared from three equivalents of the 7,7′-di-t-butylVANOL ligand, one equivalent of N-methylimidazole and one equivalent of zirconium tetraisopropoxide. This catalyst was most efficient in the presence of 10 mol% benzoic acid. Optimal conditions for aryl aldehydes required the use of 3,5-diisopropyl-2-hydroxyaniline and gave the aryl α-aminophosphonates in up to 96% yield and 98% ee over 11 different aryl aldehydes. The best aniline for aliphatic aldehydes was found to be 3-t-butyl-2-hydroxyaniline and gave the corresponding phosphonates in up to 83% yield and 97% ee over 18 examples. The asymmetric inductions for aliphatic aldehydes were comparable with those for aromatic aldehydes with a mean induction of 90% ee for the former and 91% ee for the latter. The best method for the liberation of the free amine from the aniline substituted α-aminophosphonates involved oxidation with N-iodosuccinimide., An effective catalyst has been developed for the three-component reaction of aldehydes, anilines and phosphites in an asymmetric catalytic Kabachnik–Fields reaction to give α-aminophosphonates.
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- 2021
9. A Near‐Infrared Photoswitchable Protein–Fluorophore Tag for No‐Wash Live Cell Imaging
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Wei Sheng, Elizabeth M. Santos, Babak Borhan, Xin-Liang Ding, Setare Tahmasebi Nick, Jun Zhang, James H. Geiger, and Chrysoula Vasileiou
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0301 basic medicine ,Fluorophore ,Photoisomerization ,Infrared Rays ,Imine ,01 natural sciences ,Catalysis ,Article ,chemistry.chemical_compound ,03 medical and health sciences ,Live cell imaging ,Bathochromic shift ,Humans ,Fluorescent Dyes ,Photoswitch ,Molecular Structure ,Chemistry ,010405 organic chemistry ,Optical Imaging ,Proteins ,General Chemistry ,General Medicine ,Chromophore ,Photochemical Processes ,Fluorescence ,0104 chemical sciences ,030104 developmental biology ,Biophysics ,HeLa Cells - Abstract
FR-1V, a fluorene-based aldehydic chromophore, binds its target protein as an imine to yield a highly bathochromic pigment, CF-2, a prototypic protein-dye tagging system whose NIR emission can be spatiotemporally switched ON by rapid UV-light activation. This is achieved through photoisomerization of the imine and its subsequent protonation. We demonstrate a no-wash protocol for live cell imaging of subcellular compartments in a variety of mammalian cell lines with minimal fluorescence background.
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- 2018
10. Absolute Stereochemical Determination of Organic Molecules through Induction of Helicity in Host-Guest Complexes
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Babak Borhan, Jun Zhang, Hadi Gholami, and Debarshi Chakraborty
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Supramolecular chirality ,Circular dichroism ,010405 organic chemistry ,Chemistry ,Absolute configuration ,Molecular asymmetry ,General Medicine ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Porphyrin ,0104 chemical sciences ,chemistry.chemical_compound ,Computational chemistry ,Molecular property ,Molecule ,Chirality (chemistry) - Abstract
Stereochemistry is a fundamental molecular property with important ramifications for structure, function, and activity of organic molecules. The basic building blocks of living organisms (amino acids and sugars) exhibit a precisely selected set of molecular handedness that has evolved over millions of years. The absolute stereochemistry of these building blocks is manifested in the structure and function of the cell machinery (e.g., enzymes, proteins, etc.), which are essential components of life. In the many chemical subdisciplines, molecular stereochemistry is exceedingly important and is often a strong determinant of structure and function. Besides its biological implications, the centrally important role of stereochemistry in many disciplines of chemistry and related fields has led to tremendous effort and activity, highlighted by the success in stereoselective syntheses of a host of functionalities. In the present climate, it is often the difficulty of assigning absolute stereochemistry as opposed to synthesis, which has become a nontrivial challenge, requiring the attention of the community. There will not be a general solution to this problem, as each system will have its own unique requirements and challenges; however, the need for rapid, routine, and microscale analysis is apparent. This is especially true with parallel and high-throughput arrays for screening conditions and catalysts, generating a large number of samples that require analysis.In this Account, we summarize our contribution to this field through the development of molecular receptors for sensing molecular asymmetry. These methodologies strive to unambiguously assign the absolute configuration of asymmetric center(s). To accomplish this task, our laboratory has designed a variety of host molecules, bearing various binding elements, to form stable complexes with chiral molecules (guests). During this complexation event, the stereochemistry of a target molecule induces a supramolecular chirality (i.e., helicity) within the host system. The design of the host system is such that the helicity of the host/guest complex can be observed and assigned via Exciton Coupled Circular Dichroism (ECCD), a nonempirical technique for identifying handedness, which is correlated back to the absolute stereochemistry of the bound chiral molecule. Taking advantage of the high sensitivity of chiroptical techniques (in terms of the required amount of sample for analysis) and fast response time, these methodologies offer a microscale, rapid, and nonempirical solution for assignment of absolute stereochemistry.The first part of this Account describes application of porphyrin tweezers as reporters of chirality for the absolute stereochemical determination of various classes of organic molecules. This methodology is suitable to report the absolute configuration of organic molecules that contain two binding elements (nitrogen or oxygen based functionalities). In the second part, host systems that do not require two sites of attachment to form ECCD active complexes will be described. This enables the absolute stereochemical assignment of challenging chiral molecules with functional groups lacking routine techniques for analysis.
- Published
- 2021
11. Free-Energy-Based Protein Design: Re-Engineering Cellular Retinoic Acid Binding Protein II Assisted by the Moveable-Type Approach
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Haizhen A. Zhong, Zheng Zheng, Chrysoula Vasileiou, Elizabeth M. Santos, James H. Geiger, Kenneth M. Merz, and Babak Borhan
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0301 basic medicine ,Receptors, Retinoic Acid ,Protein design ,Molecular Dynamics Simulation ,Ligands ,Protein Engineering ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Article ,Catalysis ,03 medical and health sciences ,Molecular dynamics ,Colloid and Surface Chemistry ,Cellular Retinoic Acid-Binding Protein II ,Binding site ,Retinoic acid binding ,Receptor ,Chemistry ,Mutagenesis ,General Chemistry ,Protein engineering ,0104 chemical sciences ,030104 developmental biology ,Biophysics ,Thermodynamics - Abstract
How to fine-tune the binding free energy of a small-molecule to a receptor site by altering the amino acid residue composition is a key question in protein engineering. Indeed, the ultimate solution to this problem, to chemical accuracy (±1 kcal/mol), will result in profound and wide-ranging applications in protein design. Numerous tools have been developed to address this question using knowledge-based models to more computationally intensive molecular dynamics simulations-based free energy calculations, but while some success has been achieved there remains room for improvement in terms of overall accuracy and in the speed of the methodology. Here we report a fast, knowledge-based movable-type (MT)-based approach to estimate the absolute and relative free energy of binding as influenced by mutations in a small-molecule binding site in a protein. We retrospectively validate our approach using mutagenesis data for retinoic acid binding to the Cellular Retinoic Acid Binding Protein II (CRABPII) system and then make prospective predictions that are borne out experimentally. The overall performance of our approach is supported by its success in identifying mutants that show high or even sub-nano-molar binding affinities of retinoic acid to the CRABPII system.
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- 2018
12. Absolute and relative facial selectivities in organocatalytic asymmetric chlorocyclization reactions
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Roozbeh Yousefi, Arvind Jaganathan, Kumar Dilip Ashtekar, Nastaran Salehi Marzijarani, James E. Jackson, and Babak Borhan
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chemistry.chemical_classification ,010405 organic chemistry ,Alkene ,Stereochemistry ,Carboxylic acid ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Asymmetric induction ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Syn and anti addition ,chemistry ,Nucleophile ,Amide ,Electrophile - Abstract
Though (DHQD)2PHAL-catalyzed chlorocyclizations of 1,1-disubstituted olefins show useful (and in some cases, reversible) asymmetric induction, stereochemically complete descriptions of these alkene additions have remained largely unknown. Herein, based on a combination of NMR, derivative, isotope labeling, and computational studies, we present detailed stereochemical analyses of chlorocyclizations of nucleophile-tethered 1,1-disubstituted styryl systems. The selectivities of the two asymmetric bond-forming processes, namely electrophilic chlorine attack and nucleophilic ring closure, are thus mapped out independently. Under the established optimal conditions, four related chlorocyclizations were subjected to this analysis. All showed a strong preference for Cl+ delivery from the same face of the alkene. However, depending on reaction conditions and substrate identity (carboxylic acid, amide or carbamate), the internal nucleophiles may close with a strong net preference for either syn or anti addition relative to the Cl atom. Studies of both uncatalyzed and (DHQD)2PHAL-catalyzed processes place new boundary conditions on the role of the catalyst in these reactions.
- Published
- 2018
13. Engineering the hCRBPII Domain-Swapped Dimer into a New Class of Protein Switches
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Xiangshu Jin, Alireza Ghanbarpour, Cody Pinger, James H. Geiger, Elizabeth M. Santos, Babak Borhan, Zahra Assar, Chrysoula Vasileiou, Meisam Nosrati, Kathryn Pawlowski, Rahele Esmatpour Salmani, and Dana M. Spence
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Models, Molecular ,Threonine ,Dimer ,Allosteric regulation ,Computational biology ,010402 general chemistry ,Crystallography, X-Ray ,Ligands ,Protein Engineering ,01 natural sciences ,Biochemistry ,Catalysis ,Article ,Domain (software engineering) ,Biological pathway ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Allosteric Regulation ,Protein Domains ,Disulfides ,Binding Sites ,Circular Dichroism ,Retinol-Binding Proteins, Cellular ,General Chemistry ,0104 chemical sciences ,Zinc ,chemistry ,Metals ,Mutation ,Key (cryptography) ,Tyrosine ,Protein Multimerization - Abstract
Protein conformational switches or allosteric proteins play a key role in the regulation of many essential biological pathways. Nonetheless, the implementation of protein conformational switches in protein design applications has proven challenging, with only a few known examples that are not derivatives of naturally occurring allosteric systems. We have discovered that the domain-swapped (DS) dimer of hCRBPII undergoes a large and robust conformational change upon retinal binding, making it a potentially powerful template for the design of protein conformational switches. Atomic resolution structures of the apo- and holo-forms illuminate a simple, mechanical movement involving sterically driven torsion angle flipping of two residues that drive the motion. We further demonstrate that the conformational "readout" can be altered by addition of cross-domain disulfide bonds, also visualized at atomic resolution. Finally, as a proof of principle, we have created an allosteric metal binding site in the DS dimer, where ligand binding results in a reversible 5-fold loss of metal binding affinity. The high resolution structure of the metal-bound variant illustrates a well-formed metal binding site at the interface of the two domains of the DS dimer and confirms the design strategy for allosteric regulation.
- Published
- 2019
14. Total Synthesis of (-)-Salinosporamide A via a Late Stage C-H Insertion
- Author
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Hadi Gholami, Aman Kulshrestha, Olivia K. Favor, Richard J. Staples, and Babak Borhan
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Steric effects ,Molecular Structure ,010405 organic chemistry ,Stereochemistry ,Late stage ,Total synthesis ,General Chemistry ,General Medicine ,010402 general chemistry ,01 natural sciences ,Catalysis ,Article ,0104 chemical sciences ,chemistry.chemical_compound ,Lactones ,chemistry ,Insertion reaction ,Proteasome inhibitor ,medicine ,Pyrroles ,Hydroamination ,Salinosporamide A ,Proteasome Inhibitors ,medicine.drug - Abstract
The synthesis of (-)-salinosporamide A, a proteasome inhibitor, is described. The synthesis highlights the assembly of a densely decorated pyrrolidinone core via an aza-Payne/hydroamination sequence. Central to the success of the synthesis is a late-stage C-H insertion reaction to functionalize a sterically encumbered secondary carbon. The latter functionalization leads to an enabling transformation where most of the prototypical strategies failed.
- Published
- 2019
15. Mimicking Microbial Rhodopsin Isomerization in a Single Crystal
- Author
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Alireza Ghanbarpour, Muath Nairat, Meisam Nosrati, Elizabeth M. Santos, Chrysoula Vasileiou, Marcos Dantus, Babak Borhan, and James H. Geiger
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0301 basic medicine ,Models, Molecular ,Light ,Protein Conformation ,Movement ,Temperature ,Stereoisomerism ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,Article ,0104 chemical sciences ,03 medical and health sciences ,030104 developmental biology ,Colloid and Surface Chemistry ,Biomimetics ,Bacteriorhodopsins - Abstract
Bacteriorhodopsin represents the simplest, and possibly most abundant, phototropic system requiring only a retinal-bound transmembrane protein to convert photons of light to an energy-generating proton gradient. The creation and interrogation of a microbial rhodopsin mimic, based on an orthogonal protein system, would illuminate the design elements required to generate new photoactive proteins with novel function. We describe a microbial rhodopsin mimic, created using a small soluble protein as a template, that specifically photoisomerizes all- trans to 13- cis retinal followed by thermal relaxation to the all- trans isomer, mimicking the bacteriorhodopsin photocycle, in a single crystal. The key element for selective isomerization is a tuned steric interaction between the chromophore and protein, similar to that seen in the microbial rhodopsins. It is further demonstrated that a single mutation converts the system to a protein photoswitch without chromophore photoisomerization or conformational change.
- Published
- 2018
16. A Photoisomerizing Rhodopsin Mimic Observed at Atomic Resolution
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Meisam Nosrati, James H. Geiger, Tetyana Berbasova, Chrysoula Vasileiou, and Babak Borhan
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Models, Molecular ,0301 basic medicine ,Rhodopsin ,Opsin ,genetic structures ,Photoisomerization ,Protein Conformation ,Receptors, Retinoic Acid ,Imine ,Molecular Conformation ,Protein Engineering ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Biochemistry ,Article ,Catalysis ,03 medical and health sciences ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Protein structure ,Isomerism ,Biomimetic Materials ,Humans ,biology ,Chemistry ,Bacteriorhodopsin ,General Chemistry ,Chromophore ,Photochemical Processes ,0104 chemical sciences ,030104 developmental biology ,Mutation ,biology.protein ,sense organs ,Isomerization - Abstract
The members of the rhodopsin family of proteins are involved in many essential light-dependent processes in biology. Specific photoisomerization of the protein-bound retinylidene PSB at a specified wavelength range of light is at the heart of all of these systems. Nonetheless, it has been difficult to reproduce in an engineered system. We have developed rhodopsin mimics, using intracellular lipid binding protein family members as scaffolds, to study fundamental aspects of protein/chromophore interactions. Herein we describe a system that specifically isomerizes the retinylidene protonated Schiff base both thermally and photochemically. This isomerization has been characterized at atomic resolution by quantitatively interconverting the isomers in the crystal both thermally and photochemically. This event is accompanied by a large pK(a) change of the imine similar to the pK(a) changes observed in bacteriorhodopsin and visual opsins during isomerization.
- Published
- 2016
17. Host–Guest Assembly of a Molecular Reporter with Chiral Cyanohydrins for Assignment of Absolute Stereochemistry
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Mercy Anyika, Hadi Gholami, Chrysoula Vasileiou, Jun Zhang, and Babak Borhan
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Circular dichroism ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Binding pocket ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Porphyrin ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Cyanohydrin - Abstract
The absolute stereochemistry of cyanohydrins, derived from ketones and aldehydes, is obtained routinely, in a microscale and derivatization-free manner, upon their complexation with Zn-MAPOL, a zincated porphyrin host with a binding pocket comprised of a biphenol core. The host-guest complex leads to observable exciton-coupled circular dichroism (ECCD), the sign of which is easily correlated to the absolute stereochemistry of the bound cyanohydrin. A working model, based on the ECCD signal of cyanohydrins with known configuration, is proposed.
- Published
- 2016
18. Highly Stereoselective Intermolecular Haloetherification and Haloesterification of Allyl Amides
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Richard J. Staples, Arvind Jaganathan, Bardia Soltanzadeh, and Babak Borhan
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chemistry.chemical_classification ,Esterification ,Halogenation ,Chemistry ,Alkene ,Enantioselective synthesis ,Allyl compound ,Regioselectivity ,food and beverages ,Stereoisomerism ,General Chemistry ,General Medicine ,Amides ,Article ,Catalysis ,Allyl Compounds ,Nucleophile ,Organocatalysis ,Organic chemistry ,Ethers - Abstract
An organocatalytic and highly regio-, diastereo-, and enantioselective intermolecular haloetherification and haloesterification reaction of allyl amides is reported. A variety of alkene substituents and substitution patterns are compatible with this chemistry. Notably, electronically unbiased alkene substrates exhibit exquisite regio- and diastereoselectivity for the title transformation. We also demonstrate that the same catalytic system can be used in both chlorination and bromination reactions of allyl amides with a variety of nucleophiles with little or no modification.
- Published
- 2015
19. Sensing Remote Chirality: Stereochemical Determination of β-, γ-, and δ-Chiral Carboxylic Acids
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Mercy Anyika, Marina Tanasova, and Babak Borhan
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chemistry.chemical_classification ,Models, Molecular ,Circular dichroism ,Stereochemistry ,Chemistry ,Carboxylic acid ,Carboxylic Acids ,Stereoisomerism ,General Chemistry ,General Medicine ,Small molecule ,Porphyrin ,Catalysis ,Stereocenter ,chemistry.chemical_compound ,Tweezers ,Chirality (chemistry) ,Cotton effect - Abstract
Determining the absolute stereochemisty of small molecules bearing remote nonfunctionalizable stereocenters is a challenging task. Presented is a solution in which appropriately substituted bis(porphyrin) tweezers are used. Complexation of a suitably derivatized β-, γ-, or δ-chiral carboxylic acid to the tweezer induces a predictable helicity of the bis(porphyrin), which is detected as a bisignate Cotton Effect (ECCD). The sign of the ECCD curve is correlated with the absolute stereochemistry of the substrate based on the derived working mnemonics in a predictable manner.
- Published
- 2015
20. Highly Regio- and Enantioselective Vicinal Dihalogenation of Allyl Amides
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Richard J. Staples, Hajoon Yi, Arvind Jaganathan, Bardia Soltanzadeh, Babak Borhan, and Yi Yi
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Halogenation ,Stereoisomerism ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,Article ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Organic chemistry ,Alkyl ,chemistry.chemical_classification ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Hydrocarbons, Halogenated ,Aryl ,Enantioselective synthesis ,Regioselectivity ,General Chemistry ,Amides ,0104 chemical sciences ,Allyl Compounds ,Vicinal - Abstract
We report a highly regio-, diastereo- and enantioselective vicinal dihalogenation of allyl amides. E- and Z-alkenes with both aryl and alkyl substituents were compatible with this chemistry. This is the result of exquisite catalyst controlled regioselectivity enabling use of electronically unbiased substrates. The reaction employs commercially available catalysts and halenium sources along with cheap inorganic halide salts to affect this transformation. A preliminary effort to extend this chemistry to heterodihalogenation is also presented.
- Published
- 2017
21. A New Tool To Guide Halofunctionalization Reactions: The Halenium Affinity (HalA) Scale
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Nastaran Salehi Marzijarani, James E. Jackson, Daniel Holmes, Kumar Dilip Ashtekar, Babak Borhan, and Arvind Jaganathan
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Steric effects ,Ions ,Models, Molecular ,Halogenation ,010405 organic chemistry ,Ether oxygen ,Chemistry ,Scale (chemistry) ,General Chemistry ,Alkenes ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,Article ,0104 chemical sciences ,Colloid and Surface Chemistry ,Halogens ,Nucleophile ,Computational chemistry ,Organic chemistry ,Thermodynamics ,Indicators and Reagents ,Lewis acids and bases ,Chemoselectivity - Abstract
We introduce a previously unexplored parameter—halenium affinity (HalA)– as a quantitative descriptor of the bond strengths of various functional groups to halenium ions. The HalA scale ranks potential halenium ion acceptors based on their ability to stabilize a “free halenium ion”. Alkenes in particular but other Lewis bases as well, such as amines, amides, carbonyls, and ether oxygen atoms, etc., have been classified on the HalA scale. This indirect approach enables a rapid and straightforward prediction of chemoselectivity for systems involved in halofunctionalization reactions that have multiple nucleophilic sites. The influences of subtle electronic and steric variations, as well as the less predictable anchimeric and stereoelectronic effects, are intrinsically accounted for by HalA computations, providing quantitative assessments beyond simple “chemical intuition”. This combined theoretical–experimental approach offers an expeditious means of predicting and identifying unprecedented reactions.
- Published
- 2014
22. Point-to-Axial Chirality Transfer—A New Probe for 'Sensing' the Absolute Configurations of Monoamines
- Author
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Kumar Dilip Ashtekar, Robert Acho, Mercy Anyika, Babak Borhan, and Hadi Gholami
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Steric effects ,Chemistry ,Stereochemistry ,Diastereomer ,General Chemistry ,Dichroic glass ,Biochemistry ,Helicity ,Catalysis ,Colloid and Surface Chemistry ,Molecular recognition ,Axial chirality ,Chemical physics ,Molecule ,Physics::Chemical Physics ,Chirality (chemistry) - Abstract
A host molecule, capable of freely adopting P or M helicity, is described for molecular recognition and chirality sensing. The host, consisting of a biphenol core, binds chiral amines via hydrogen-bonding interactions. The diastereomeric complex will favor either P or M helicity as a result of minimizing steric interactions of the guest molecule with the binding cavity of the host, resulting in a detectable exciton-coupled circular dichroic spectrum. A working model is proposed that enables non-empirical prediction of the chirality of the bound amine.
- Published
- 2014
23. Back Cover: Total Synthesis of (−)‐Salinosporamide A via a Late Stage C−H Insertion (Angew. Chem. Int. Ed. 30/2019)
- Author
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Olivia K. Favor, Hadi Gholami, Babak Borhan, Richard J. Staples, and Aman Kulshrestha
- Subjects
chemistry.chemical_compound ,chemistry ,Stereochemistry ,INT ,Late stage ,Total synthesis ,Cover (algebra) ,General Chemistry ,Hydroamination ,Salinosporamide A ,Catalysis - Published
- 2019
24. Rational Design of a Colorimetric pH Sensor from a Soluble Retinoic Acid Chaperone
- Author
-
James H. Geiger, Tetyana Berbasova, Babak Borhan, Meisam Nosrati, Ipek Yapici, Chrysoula Vasileiou, Kin Sing Stephen Lee, and Wenjing Wang
- Subjects
Models, Molecular ,Receptors, Retinoic Acid ,Stereochemistry ,Molecular Conformation ,Retinoic acid ,Protonation ,Crystallography, X-Ray ,Protein Engineering ,Biochemistry ,Article ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Humans ,Schiff base ,biology ,Rational design ,Iminium ,Retinal ,General Chemistry ,Hydrogen-Ion Concentration ,chemistry ,Chaperone (protein) ,Mutation ,biology.protein ,Colorimetry ,Protein Binding ,Visible spectrum - Abstract
Reengineering of cellular retinoic acid binding protein II (CRABPII) to be capable of binding retinal as a protonated Schiff base is described. Through rational alterations of the binding pocket, electrostatic perturbations of the embedded retinylidene chromophore that favor delocalization of the iminium charge lead to exquisite control in the regulation of chromophoric absorption properties, spanning the visible spectrum (474-640 nm). The pKa of the retinylidene protonated Schiff base was modulated from 2.4 to 8.1, giving rise to a set of proteins of varying colors and pH sensitivities. These proteins were used to demonstrate a concentration-independent, ratiometric pH sensor.
- Published
- 2013
25. Kinetic Resolution of Unsaturated Amides in a Chlorocyclization Reaction: Concomitant Enantiomer Differentiation and Face Selective Alkene Chlorination by a Single Catalyst
- Author
-
Richard J. Staples, Babak Borhan, and Arvind Jaganathan
- Subjects
chemistry.chemical_classification ,Olefin fiber ,Halogenation ,Chemistry ,Alkene ,Stereoisomerism ,General Chemistry ,Alkenes ,Amides ,Biochemistry ,Catalysis ,Kinetic resolution ,Kinetics ,Colloid and Surface Chemistry ,Cyclization ,Organic chemistry ,Lewis acids and bases ,Enantiomer ,Chirality (chemistry) ,Selectivity - Abstract
The first example of a kinetic resolution via chlorofunctionalization of olefins is reported. The enantiomers of racemic unsaturated amides were found to have different hydrogen-bonding affinities for chiral Lewis bases in numerous solvents. This interaction was exploited in developing a kinetic resolution of racemic unsaturated amides via halocyclization. The same catalyst serves to both "sense chirality" in the substrate as well as mediate a highly face-selective chlorine delivery onto the olefin functionality, resulting in stereotriad products in up to 99:1 dr and up to 98.5:1.5 er. The selectivity factors were typically greater than 50 to allow for the simultaneous synthesis of both the products and unreacted substrates in highly enantioenriched form at yields approaching 50%. The reaction employs catalytic amounts (≤0.50 mol %) of a commercially available and recyclable organocatalyst.
- Published
- 2013
26. Solvent-Dependent Enantiodivergence in the Chlorocyclization of Unsaturated Carbamates
- Author
-
Arvind Jaganathan, Nastaran Salehi Marzijarani, James E. Jackson, Daniel C. Whitehead, Atefeh Garzan, Roozbeh Yousefi, and Babak Borhan
- Subjects
Solvent system ,Solvent ,Chemistry ,Organocatalysis ,Organic Chemistry ,Organic chemistry ,General Chemistry ,Eyring equation ,Selectivity ,Catalysis - Abstract
A remarkable solvent-controlled enantiodivergence is seen in the hydroquinidine 1,4-phthalazinediyl diether ((DHQD)2PHAL)-catalyzed chlorocyclization of unsaturated carbamates. Eyring plot analyses of this previously unreported reaction are used to probe and compare the R- and S-selective pathways. In the CHCl3/hexanes solvent system, the pro-R process shows a surprising increase in selectivity with increasing temperature. These studies point to a strongly solvent-dependent entropy-enthalpy balance between the pro-R and pro-S pathways.
- Published
- 2013
27. Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent
- Author
-
James E. Jackson, Babak Borhan, Mathew J. Vetticatt, Kumar Dilip Ashtekar, and Roozbeh Yousefi
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Alkene ,Enantioselective synthesis ,Context (language use) ,General Chemistry ,Alkenes ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,Catalysis ,Article ,0104 chemical sciences ,Stereocenter ,Electron Transport ,Colloid and Surface Chemistry ,Nucleophile ,Cyclization ,Kinetic isotope effect ,Reactivity (chemistry) - Abstract
Emerging work on organocatalytic enantioselective halocyclizations naturally draws on conditions where both new bonds must be formed under delicate control, the reaction regime where the concerted nature of the AdE3 mechanism is of greatest importance. Without assistance, many simple alkene substrates react slowly or not at all with conventional halenium donors under synthetically relevant reaction conditions. As demonstrated earlier by Shilov, Cambie, Williams, Fahey, and others, alkenes can undergo a concerted AdE3-type reaction via nucleophile participation, which sets the configuration of the newly created stereocenters at both ends in one step. Herein, we explore the modulation of alkene reactivity and halocyclization rates by nucleophile proximity and basicity, through detailed analyses of starting material spectroscopy, addition stereopreferences, isotope effects, and nucleophile–alkene interactions, all obtained in a context directly relevant to synthesis reaction conditions. The findings build on the prior work by highlighting the reactivity spectrum of halocyclizations from stepwise to concerted, and suggest strategies for design of new reactions. Alkene reactivity is seen to span the range from the often overgeneralized “sophomore textbook” image of stepwise electrophilic attack on the alkene and subsequent nucleophilic bond formation, to the nucleophile-assisted alkene activation (NAAA) cases where electron donation from the nucleophilic addition partner activates the alkene for electrophilic attack. By highlighting the factors that control reactivity across this range, this study suggests opportunities to explain and control stereo-, regio-, and organocatalytic chemistry in this important class of alkene additions.
- Published
- 2016
28. Absolute Configuration for 1,n-Glycols: A Nonempirical Approach to Long-Range Stereochemical Determination
- Author
-
Richard J. Staples, Carmin E. Burrell, Xiaoyong Li, and Babak Borhan
- Subjects
Models, Molecular ,Circular dichroism ,Porphyrins ,Chemistry ,Stereochemistry ,Circular Dichroism ,Diol ,Absolute configuration ,Stereoisomerism ,General Chemistry ,Crystallography, X-Ray ,Biochemistry ,Porphyrin ,Catalysis ,Glycols ,Crystallography ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Organometallic Compounds ,Molecule ,Derivatization ,Group 2 organometallic chemistry - Abstract
The absolute configurations of 1,n-glycols (n = 2-12, 16) bearing two chiral centers were rapidly determined via exciton-coupled circular dichroism (ECCD) using a tris(pentafluorophenyl)porphyrin (TPFP porphyrin) tweezer system in a nonempirical fashion devoid of chemical derivatization. A unique "side-on" approach of the porphyrin tweezer relative to the diol guest molecule is suggested as the mode of complexation.
- Published
- 2012
29. Probing Wavelength Regulation with an Engineered Rhodopsin Mimic and a C15-Retinal Analogue
- Author
-
Tetyana Berbasova, Chrysoula Vasileiou, Kin Sing Stephen Lee, Wenjing Wang, James H. Geiger, Farid Nossoni, Xiaofei Jia, Babak Borhan, and Yoomi Choi
- Subjects
chemistry.chemical_compound ,biology ,chemistry ,Biochemistry ,Rhodopsin ,biology.protein ,Bioorganic chemistry ,Mutagenesis (molecular biology technique) ,Retinal ,General Chemistry ,Protein engineering ,Transport protein - Published
- 2012
30. A Catalytic Asymmetric Chlorocyclization of Unsaturated Amides
- Author
-
Richard J. Staples, Babak Borhan, Arvind Jaganathan, Atefeh Garzan, and Daniel C. Whitehead
- Subjects
chemistry.chemical_compound ,chemistry ,Amide ,Organocatalysis ,Organic chemistry ,General Medicine ,General Chemistry ,Oxazoline ,Catalysis - Published
- 2011
31. Cover Picture: Ultrafast Dynamics of a 'Super' Photobase (Angew. Chem. Int. Ed. 45/2018)
- Author
-
James H. Geiger, Benjamin Farris, Patrick D. Pawlaczyk, Elizabeth Mroczka, Babak Borhan, Ehud Pines, Marcos Dantus, Wei Sheng, and Muath Nairat
- Subjects
Physics ,chemistry.chemical_compound ,chemistry ,Chemical physics ,Excited state ,Cover (algebra) ,General Chemistry ,Fluorene ,Ultrashort pulse ,Catalysis ,Transient spectroscopy - Published
- 2018
32. Fluorinated Porphyrin Tweezer: A Powerful Reporter of Absolute Configuration forerythroandthreoDiols, Amino Alcohols, and Diamines
- Author
-
Chrysoula Vasileiou, Babak Borhan, Xiaoyong Li, and Marina Tanasova
- Subjects
Models, Molecular ,Steric effects ,Molecular Structure ,Metalloporphyrins ,Stereochemistry ,Static Electricity ,Supramolecular chemistry ,Absolute configuration ,Diastereomer ,Stereoisomerism ,General Chemistry ,Diamines ,Ring (chemistry) ,Amino Alcohols ,Binding, Competitive ,Biochemistry ,Porphyrin ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Alcohols ,Chirality (chemistry) - Abstract
A general and sensitive nonempirical protocol to determine the absolute configurations of erythro and threo diols, amino alcohols, and diamines is reported. Binding of diols to the porphyrin tweezer system is greatly enhanced by increasing the Lewis acidity of the metalloporphyrin. Supramolecular complexes formed between the porphyrin tweezer host and chiral substrates exhibited exciton-coupled bisignate CD spectra with predictable signs based on the substituents on the chiral center. The working model suggests that the observed helicity of the porphyrin tweezer is dictated via steric differentiation experienced by the porphyrin ring bound to each chiral center. A variety of erythro and threo substrates were investigated to verify this chiroptical method. Their absolute configurations were unequivocally determined, and thus a general mnemonic is provided for the assignment of chirality.
- Published
- 2008
33. 'Turn-on' protein fluorescence: in situ formation of cyanine dyes
- Author
-
Kin Sing Stephen Lee, Tetyana Berbasova, Chrysoula Vasileiou, Xiaofei Jia, Wenjing Wang, James H. Geiger, Ipek Yapici, Babak Borhan, Meisam Nosrati, and Elizabeth M. Santos
- Subjects
Models, Molecular ,Molecular Structure ,Chemistry ,Stereochemistry ,Receptors, Retinoic Acid ,Kinetics ,Mutant ,General Chemistry ,Plasma protein binding ,Chromophore ,Carbocyanines ,Hydrogen-Ion Concentration ,Biochemistry ,Fluorescence ,Catalysis ,Article ,Transport protein ,Turn (biochemistry) ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Biophysics ,Cyanine ,Coloring Agents - Abstract
Protein reengineering of cellular retinoic acid binding protein II (CRABPII) has yielded a genetically addressable system, capable of binding a profluorophoric chromophore that results in fluorescent protein/chromophore complexes. These complexes exhibit far-red emission, with high quantum efficiencies and brightness and also exhibit excellent pH stability spanning the range of 2–11. In the course of this study, it became evident that single mutations of L121E and R59W were most effective in improving the fluorescent characteristics of CRABPII mutants as well as the kinetics of complex formation. The readily crystallizable nature of these proteins was invaluable to provide clues for the observed spectroscopic behavior that results from single mutation of key residues.
- Published
- 2014
34. An Organocatalytic Asymmetric Chlorolactonization
- Author
-
Arvind Jaganathan, Roozbeh Yousefi, Daniel C. Whitehead, and Babak Borhan
- Subjects
Chromatography ,Chemistry ,Hydantoins ,Enantioselective synthesis ,Stereoisomerism ,General Chemistry ,Biochemistry ,Combinatorial chemistry ,Article ,Catalysis ,Fatty Acids, Monounsaturated ,Lactones ,Colloid and Surface Chemistry ,Cyclization ,Reagent ,Hydrocarbons, Chlorinated - Abstract
A reagent controlled organocatalytic enantioselective chlorolactonization reaction has been developed. Several 4-aryl pentenoic acids were cyclized in the presence of 0.1 equiv of (DHQD)(2)PHAL, employing various N-chlorinated hydantoins as the terminal chlorenium source. Ten examples are presented with selectivities ranging from 43 to 90% ee. This work represents the first example of an enantioselective reagent-controlled chlorolactonization that approaches synthetically useful enantioselectivities.
- Published
- 2010
35. Efficient Synthesis of 11-cis-Retinoids
- Author
-
Bishan Zhou, Koji Nakanishi, Babak Borhan, Joann Um, and Maria L. Souto
- Subjects
Ideal (set theory) ,biology ,Chemistry ,Organic Chemistry ,chemistry.chemical_element ,General Chemistry ,Zinc ,Chromophore ,Photochemistry ,Catalysis ,Computational chemistry ,Rhodopsin ,biology.protein ,Visual phototransduction - Abstract
The light sensitivity and unstable nature of 11-cis-retinoids makes them ideal visual chromophores in nature. The synthesis of 11-cis-retinal analogues is of paramount importance in bioorganic studies of rhodopsin, the photoreceptor of the visual transduction pathway, but the instability of 11-cis-retinoids complicates their synthesis and there is no general synthetic route. Common strategies to the cis geometry have failed in the case of 11-cis-retinoids, and most often low yields and complex isomeric mixtures are obtained. Herein we report an efficient, general, and mild preparation of 11-cis-retinoids by semi-hydrogenation of 11-yne-retinoid precursors with Cu/Ag-activated zinc dust.
- Published
- 1999
36. Absolute Sense of Twist of the C12C13 Bond of the Retinal Chromophore in Bovine Rhodopsin Based on Exciton-Coupled CD Spectra of 11,12-Dihydroretinal Analogues
- Author
-
Jihong Lou, Elena Karnaukhova, Koji Nakanishi, Babak Borhan, Qiang Tan, and Nina Berova
- Subjects
Circular dichroism ,biology ,Stereochemistry ,Chemistry ,Exciton ,General Medicine ,General Chemistry ,Catalysis ,Spectral line ,Absolute sense ,Rhodopsin ,biology.protein ,Twist ,Chirality (chemistry) ,Retinal chromophore - Published
- 1997
37. Dissecting the stereocontrol elements of a catalytic asymmetric chlorolactonization: syn addition obviates bridging chloronium
- Author
-
Roozbeh Yousefi, James E. Jackson, Daniel C. Whitehead, Kumar Dilip Ashtekar, and Babak Borhan
- Subjects
chemistry.chemical_classification ,Double bond ,Chemistry ,Stereochemistry ,Enantioselective synthesis ,General Chemistry ,Nuclear magnetic resonance spectroscopy ,Biochemistry ,Catalysis ,Stereocenter ,Isotopic labeling ,Colloid and Surface Chemistry ,Syn and anti addition ,Nucleophile ,Lactone - Abstract
We report absolute and relative stereochemistry of addition in enantioselective chlorolactonizations of 4-phenyl-4-pentenoic acid and its related t-butyl ester, catalyzed by (DHQD)2PHAL. Predominant syn addition of the chlorenium and the nucleophile across the olefin is observed. As shown by isotopic labeling, NMR spectroscopy, and derivative studies, the two new stereocenters formed by addition across the double bond are set independently and influenced by different factors. These findings suggest a stepwise process via an intermediate capable of lactone closure with either stereochemistry, in contradistinction to the more familiar scenario in which anti addition is dictated by a bridging chloronium ion intermediate.
- Published
- 2013
38. Selectivity in the addition reactions of organometallic reagents to aziridine-2-carboxaldehydes: the effects of protecting groups and substitution patterns
- Author
-
Jennifer M. Schomaker, James E. Jackson, Daniel Holmes, Aman Kulshrestha, Babak Borhan, and Richard J. Staples
- Subjects
Models, Molecular ,Addition reaction ,Aldehydes ,Organic Chemistry ,Aziridines ,Grignard reaction ,Molecular Conformation ,Stereoisomerism ,General Chemistry ,Aziridine ,Catalysis ,Article ,chemistry.chemical_compound ,chemistry ,Computational chemistry ,Organic chemistry ,Stereoselectivity ,Indicators and Reagents ,Lewis acids and bases ,Solvent effects ,Selectivity - Abstract
Good to excellent stereo-selectivity has been found in the addition reactions of Grignard and organo-zinc reagents to N-protected aziridine-2-carboxaldehydes. Specifically, high syn selectivity was obtained with benzyl-protected cis, tert-butyloxycar-bonyl-protected trans, and tosyl-pro-tected 2,3-disubstituted aziridine-2-car-boxaldehydes. Furthermore, rate and selectivity effects of ring substituents, temperature, solvent, and Lewis acid and base modifiers were studied. The diastereomeric preference of addition is dominated by the substrate aziri-dines’ substitution pattern and especially the electronic character and conformational preferences of the nitrogen protecting groups. To help rationalize the observed stereochemical outcomes, conformational and electronic structural analyses of a series of model systems representing the various substitution patterns have been explored by density functional calculations at the B3LYP/6–31G* level of theory with the SM8 solvation model to account for solvent effects.
- Published
- 2011
39. A minimalist NMR approach for the structural revision of mucoxin
- Author
-
Atefeh Garzan, Chrysoula Vasileiou, Radha S. Narayan, Jun Yan, and Babak Borhan
- Subjects
education.field_of_study ,Magnetic Resonance Spectroscopy ,Molecular Structure ,Stereochemistry ,Chemistry ,Organic Chemistry ,Population ,Stereoisomerism ,General Chemistry ,Nuclear magnetic resonance spectroscopy ,Carbon-13 NMR ,Catalysis ,Article ,education ,Furans - Abstract
In an attempt to revise the structural assignment of mucoxin, and faced with 64 diastereomeric possibilities, we resorted to the synthesis of truncated structures that contained the core stereochemical sites. Twelve stereochemical analogues were synthesized, their (1)H and (13)C NMR spectra were analyzed and four recurring stereochemical trends were distilled from the data. Applying the observed trends to the diastereomeric population pared the possible choices for the correct structure of mucoxin from 64 to 4. Synthesis of these analogues led to the identification of the correct structure of mucoxin.
- Published
- 2010
40. Magnetic glyco-nanoparticles: a tool to detect, differentiate, and unlock the glyco-codes of cancer via magnetic resonance imaging
- Author
-
Xuefei Huang, Davide Prosperi, Babak Borhan, Wei Li, Chrysoula Vasileiou, David C. Zhu, and Kheireddine El-Boubbou
- Subjects
Models, Molecular ,Magnetic Resonance Spectroscopy ,Carbohydrates ,Tumor cells ,Computational biology ,Biochemistry ,Catalysis ,Metastasis ,Magnetics ,Mice ,Colloid and Surface Chemistry ,Nuclear magnetic resonance ,Microscopy, Electron, Transmission ,Nanosensor ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Humans ,medicine.diagnostic_test ,Molecular Structure ,Chemistry ,Cancer ,Magnetic resonance imaging ,General Chemistry ,medicine.disease ,Magnetic Resonance Imaging ,Cell culture ,Cancer cell ,Nanoparticles ,Cancer development - Abstract
Within cancer, there is a large wealth of diversity, complexity, and information that nature has engineered rendering it challenging to identify reliable detection methods. Therefore, the development of simple and effective techniques to delineate the fine characteristics of cancer cells can have great potential impacts on cancer diagnosis and treatment. Herein, we report a magnetic glyco-nanoparticle (MGNP) based nanosensor system bearing carbohydrates as the ligands, not only to detect and differentiate cancer cells but also to quantitatively profile their carbohydrate binding abilities by magnetic resonance imaging (MRI). Using an array of MGNPs, a range of cells including closely related isogenic tumor cells, cells with different metastatic potential and malignant vs normal cells can be readily distinguished based on their respective "MRI signatures". Furthermore, the information obtained from such studies helped guide the establishment of strongly binding MGNPs as antiadhesive agents against tumors. As the interactions between glyco-conjugates and endogenous lectins present on cancer cell surface are crucial for cancer development and metastasis, the ability to characterize and unlock the glyco-code of individual cell lines can facilitate both the understanding of the roles of carbohydrates as well as the expansion of diagnostic and therapeutic tools for cancer.
- Published
- 2010
41. Prompt determination of absolute configuration for epoxy alcohols via exciton chirality protocol
- Author
-
Xiaoyong Li and Babak Borhan
- Subjects
Chemistry ,Exciton ,Circular Dichroism ,Absolute configuration ,Molecular Conformation ,Stereoisomerism ,General Chemistry ,Epoxy ,Photochemistry ,Biochemistry ,Porphyrin ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Computational chemistry ,visual_art ,Alcohols ,visual_art.visual_art_medium ,Molecule ,Epoxy Compounds ,Chirality (chemistry) ,Cis–trans isomerism ,Microscale chemistry - Abstract
A microscale protocol for determination of absolute configurations of 2,3-epoxy alcohols is described. 2,3-Disubstituted (cis and trans), 2,2-disubstituted, 2,2,3-trisubstituted, and 2,3,3-trisubstituted epoxy alcohols rendered prominent ECCD signals upon complexing with a Lewis acidic porphyrin tweezer and consequently provide straightforward assignment of chirality for epoxy alcohols. This method proved to be rapid, simple, sensitive, and reliable for the class of molecules listed above.
- Published
- 2008
42. Protein design: reengineering cellular retinoic acid binding protein II into a rhodopsin protein mimic
- Author
-
Rachael M. Crist, Chrysoula Vasileiou, James H. Geiger, Babak Borhan, Soheila Vaezeslami, and Montserrat Rabago-Smith
- Subjects
Models, Molecular ,Protein Folding ,Rhodopsin ,Stereochemistry ,Receptors, Retinoic Acid ,Protein design ,Imine ,Mutant ,Crystallography, X-Ray ,Protein Engineering ,Biochemistry ,Catalysis ,Protein Structure, Secondary ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Schiff Bases ,Schiff base ,Binding Sites ,biology ,Binding protein ,Retinal ,General Chemistry ,Transport protein ,chemistry ,Models, Chemical ,Mutation ,biology.protein ,Retinaldehyde ,Protein Binding - Abstract
Rational redesign of the binding pocket of Cellular Retinoic Acid Binding Protein II (CRABPII) has provided a mutant that can bind retinal as a protonated Schiff base, mimicking the binding observed in rhodopsin. The reengineering was accomplished through a series of choreographed manipulations to ultimately orient the reactive species (the epsilon-amino group of Lys132 and the carbonyl of retinal) in the proper geometry for imine formation. The guiding principle was to achieve the appropriate Bürgi-Dunitz trajectory for the reaction to ensue. Through crystallographic analysis of protein mutants incapable of forming the requisite Schiff base, a highly ordered water molecule was identified as a key culprit in orienting retinal in a nonconstructive manner. Removal of the ordered water, along with placing reinforcing mutations to favor the desired orientation of retinal, led to a triple mutant CRABPII protein capable of nanomolar binding of retinal as a protonated Schiff base. The high-resolution crystal structure of all-trans-retinal bound to the CRABPII triple mutant (1.2 A resolution) unequivocally illustrates the imine formed between retinal and the protein.
- Published
- 2007
43. Diastereomerically and enantiomerically pure 2,3-disubstituted pyrrolidines from 2,3-aziridin-1-ols using a sulfoxonium ylide: a one-carbon homologative relay ring expansion
- Author
-
Somnath Bhattacharjee, Jennifer M. Schomaker, Jun Yan, and Babak Borhan
- Subjects
Steric effects ,Pyrrolidines ,Aziridines ,chemistry.chemical_element ,Epoxide ,Stereoisomerism ,Ring (chemistry) ,Crystallography, X-Ray ,Biochemistry ,Catalysis ,Pyrrolidine ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Nucleophile ,Organic chemistry ,Molecule ,Reaction conditions ,chemistry.chemical_classification ,Molecular Structure ,General Medicine ,General Chemistry ,Combinatorial chemistry ,chemistry ,Ylide ,Carbon ,Dapsone - Abstract
An ylide-based aza-Payne rearrangement of 2,3-aziridin-1-ols leads to an efficient process for the preparation of pyrrolidines. The aza-Payne rearrangement under basic reaction conditions favors the formation of epoxy amines. Subsequent nucleophilic attack of the epoxide by the ylide yields a bis-anion, which upon a 5-exo-tet ring-closure yields the desired pyrrolidine, thus completing the relay of the three-membered to the five-membered nitrogen-containing ring system. This process takes place with complete transfer of stereochemical fidelity and can be applied to sterically hindered aziridinols.
- Published
- 2007
44. One-pot regio- and stereoselective cyclization of 1,2,n-triols
- Author
-
Jennifer M. Schomaker, Tao Zheng, Radha S. Narayan, and Babak Borhan
- Subjects
Chemistry ,Stereochemistry ,Regioselectivity ,General Chemistry ,Biochemistry ,Catalysis ,Acid catalysis ,Colloid and Surface Chemistry ,Intramolecular force ,Cyclic ether ,Stereoselectivity ,Lewis acids and bases ,Aliphatic compound - Abstract
A simple and efficient process to cyclize triols containing a 1,2-diol functionality with a pendant hydroxyl group is presented. The one-pot procedure converts the 1,2-diol into an ortho ester in situ, which upon treatment with a Lewis acid generates a cyclic acetoxonium intermediate. This intermediate is subsequently trapped by the pendant hydroxyl group to generate a cyclic ether. The stereochemistry of the 1,2-diol is transferred to the product with complete fidelity (inversion at the site of cyclization), and the reaction proceeds with high regioselectivity. The process is akin to the Lewis acid-catalyzed intramolecular ring-opening of epoxides with hydroxyl groups yielding cyclic ethers of various sizes with regio- and stereochemical control.
- Published
- 2005
45. Synthesis of diastereomerically and enantiomerically pure 2,3-disubstituted tetrahydrofurans using a sulfoxonium ylide
- Author
-
Babak Borhan, Veera Reddy Pulgam, and Jennifer M. Schomaker
- Subjects
Steric effects ,Sharpless epoxidation ,chemistry.chemical_classification ,Chemistry ,Regioselectivity ,General Medicine ,General Chemistry ,Ring (chemistry) ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Ylide ,Yield (chemistry) ,Nucleophilic substitution ,Organic chemistry ,Solvent effects ,Tetrahydrofuran - Abstract
Nucleophilic substitution reactions of 2,3-epoxy alcohols, easily prepared via Sharpless asymmetric epoxidation chemistry, offer access to a wide variety of enantiomerically pure compounds. In this communication, we describe the use of a Payne rearrangement to control regioselectivity in the ring-opening of a series of 2,3-epoxy alcohols with dimethylsulfoxonium methylide to yield diastereomerically and/or enantiomerically pure disubstituted tetrahydrofuran rings. The factors influencing the success and substitution pattern of the THF ring products are discussed, including steric, electronic, and solvent effects.
- Published
- 2004
46. Zinc porphyrin tweezer in host-guest complexation: determination of absolute configurations of primary monoamines by circular dichroism
- Author
-
Xuefei Huang, Nina Berova, Koji Nakanishi, Babak Borhan, and Barry H. Rickman
- Subjects
Circular dichroism ,Amino esters ,Molecular Structure ,Stereochemistry ,Metalloporphyrins ,Newman projection ,Circular Dichroism ,Organic Chemistry ,Absolute configuration ,Stereoisomerism ,General Chemistry ,Porphyrin ,Catalysis ,Stereocenter ,chemistry.chemical_compound ,chemistry ,Amines ,Chirality (chemistry) - Abstract
A nonempirical exciton chirality circular dichroic (CD) method for determining the absolute configurations of primary monoamines with amino group directly linked to the stereogenic center is described. Conventional exciton chirality CD method cannot be applied to these compounds since they lack the two sites for attaching the interacting chromophores. This was solved by covalently linking the monoamine to a trifunctional bidentate carrier moiety 1. Treatment of the carrier/monoamine conjugate with the porphyrin tweezer 4 consisting of two pentanediol-linked zinc porphyrins gives rise to 1:1 host-guest macrocyclic complexes that exhibit exciton-coupled CD spectra. The sign of the CD couplet can then be correlated with the absolute configuration of the monoamine as follows: a clockwise arrangement of the L, M, and S (large, medium, small) groups in the Newman projection of the monoamine with the amino group in the rear gives rise to a positive CD couplet, and vice versa; the assignments of L, M, S groups are based on conformational energies (A values). This method is applicable to cyclic and acyclic aliphatic amines, aromatic amines, amino esters, amides, and cyclic amino alcohols, and can be performed at the several microgram level.
- Published
- 2002
47. On the bioactive conformation of the rhodopsin chromophore: absolute sense of twist around the 6-s-cis bond
- Author
-
Shojiro Maki, Nathan Fishkin, Takumi Furuta, Koji Nakanishi, Jun Ishihara, Babak Borhan, Tao Wang, Nina Berova, Yukari Fujimoto, and Naoko Fujioka
- Subjects
Models, Molecular ,Circular dichroism ,Opsin ,Rhodopsin ,Photoisomerization ,Stereochemistry ,Protein Conformation ,Catalysis ,Protein Structure, Secondary ,chemistry.chemical_compound ,Moiety ,Animals ,biology ,Circular Dichroism ,Organic Chemistry ,Rod Opsins ,Retinal ,Stereoisomerism ,General Chemistry ,Chromophore ,chemistry ,biology.protein ,Retinaldehyde ,Cattle ,Spectrophotometry, Ultraviolet ,sense organs ,Chirality (chemistry) - Abstract
Incubation of opsin with synthetic 6-s-locked retinoids 2 a and 2 b only led to pigment formation from the alpha-locked 2 a, the CD spectrum of which was similar to that of native rhodopsin (Rh). This establishes that the 6-s-bond of the chromophore in rhodopsin is cis, and that its helicity is negative. Earlier cross-linking studies showed that the 11-cis to all-trans photoisomerization occurring in the batho-Rh to lumi-Rh conversion induces a flip over of the side carrying the ring moiety. The GTP-binding assay of pigment Rh-(2 a), incorporating retinal analogue 2 a, has shown that its activity is 80 % that of the native pigment. That is, the overall conformation around the 6-s bond is retained in the steps leading to G-protein activation.
- Published
- 2001
48. Total Synthesis of Haterumalides NA and NC via a Chromium-Mediated Macrocyclization
- Author
-
Jennifer M. Schomaker and Babak Borhan
- Subjects
Chromium ,Stereochemistry ,chemistry.chemical_element ,Stereoisomerism ,Biochemistry ,Medicinal chemistry ,Aldehyde ,Article ,Catalysis ,Colloid and Surface Chemistry ,Organometallic Compounds ,Animals ,Carbenoid ,Deoxygenation ,Group 2 organometallic chemistry ,chemistry.chemical_classification ,Aldehydes ,Chemistry ,Total synthesis ,General Chemistry ,Ethylenes ,Porifera ,Oxygen ,Cyclization ,Macrolides - Abstract
The syntheses of haterumalides NA and NC were accomplished via the macrocyclization of a chlorovinylidene chromium carbenoid onto a pendant aldehyde to generate the C8-C9 bond with the desired stereoisomer as the major product. Utilizing the latter chemistry enables access to both C9 hydroxylated (haterumalides NC and ND) and C9 deoxygenated forms (haterumalides NA, NB, and NE; via deoxygenation of the C9-hydroxyl).
- Published
- 2008
49. Engineering a Rhodopsin Protein Mimic
- Author
-
James H. Geiger, Babak Borhan, Montserrat Rabago-Smith, Chrysoula Vasileiou, and Rachael M. Crist
- Subjects
Rhodopsin ,genetic structures ,Receptors, Retinoic Acid ,Fluorescence spectrometry ,Retinoic acid ,Photoprotein ,Tretinoin ,Crystallography, X-Ray ,Protein Engineering ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Biomimetic Materials ,Humans ,Receptor ,Binding Sites ,biology ,Chemistry ,Lysine ,Binding protein ,Retinal ,General Chemistry ,Transmembrane protein ,Kinetics ,Spectrometry, Fluorescence ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,biology.protein ,Thermodynamics ,Spectrophotometry, Ultraviolet ,sense organs - Abstract
Due to the difficulties in handling and manipulating membrane-bound proteins, such as rhodopsin, and the lack of crystallographic information on the cone opsins, we have opted to engineer a protein mimic of the transmembrane G-protein coupled receptor. Human cellular retinoic acid binding protein (CRABPII), a well studied and characterized protein, has been reengineered into a protein that now will bind retinal as a protonated Schiff base with high binding affinity (Kd = 2 nM) mimicking that of rhodopsin.
- Published
- 2006
50. Circular Dichroism and Magnetic Circular Dichroism Spectroscopy for Organic Chemists. By Nagao Kobayashi, Atsuya Muranaka, and John Mack
- Author
-
Babak Borhan
- Subjects
Circular dichroism ,Nuclear magnetic resonance ,Magnetic circular dichroism ,Chemistry ,General Chemistry ,Spectroscopy ,Catalysis - Published
- 2012
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