Title: Biomacromolecule-Assisted Screening for Reaction Discovery and Catalyst Optimization
Reaction discovery and catalyst screening lie at the heart of synthetic organic chemistry. And while there are efforts at de novo catalyst design using computation/artificial intelligence; at its core, synthetic chemistry is an experimental science. This review overviews biomacromolecule-assisted screening methods and the follow-on elaboration of chemistry so discovered. All three types of biomacromolecules discussed–enzymes, antibodies, and nucleic acids–have been used as ‘sensors’ to provide a readout on product chirality exploiting their native chirality. Enzymatic sensing methods yield both UV-spectrophotometric and visible, colorimetric readouts. Antibody sensors provide direct fluorescent readout upon analyte binding in some cases, or provide for cat-ELISA (Enzyme-Linked ImmunoSorbent Assay)-type readouts. DNA biomacromolecule-assisted screening allows for templation to facilitate reaction discovery, driving bimolecular reactions into a pseudo-unimolecular format. Also, the ability to use DNA-encoded libraries permits the barcoding of reactants. All three types of biomacromolecule-based screens afford high sensitivity and selectivity. Among the chemical transformations discovered by enzymatic screening methods are the first Ni(0)-mediated asymmetric allylic amination, and a new thiocyanopalladation/carbocyclization transformation in which both C-SCN and C-C bonds are fashioned sequentially. Cat-ELISA screening has identified new classes of sydnone-alkyne cycloadditions and DNA-encoded screening has been exploited to uncover interesting oxidative Pd-mediated amido-alkyne/alkene coupling reactions. more »« less
Arcadia, Christopher E.; Dombroski, Amanda; Oakley, Kady; Chen, Shui Ling; Tann, Hokchhay; Rose, Christopher; Kim, Eunsuk; Reda, Sherief; Rubenstein, Brenda M.; Rosenstein, Jacob K.
(, Chemical Science)
null
(Ed.)
Autocatalysis is fundamental to many biological processes, and kinetic models of autocatalytic reactions have mathematical forms similar to activation functions used in artificial neural networks. Inspired by these similarities, we use an autocatalytic reaction, the copper-catalyzed azide–alkyne cycloaddition, to perform digital image recognition tasks. Images are encoded in the concentration of a catalyst across an array of liquid samples, and the classification is performed with a sequence of automated fluid transfers. The outputs of the operations are monitored using UV-vis spectroscopy. The growing interest in molecular information storage suggests that methods for computing in chemistry will become increasingly important for querying and manipulating molecular memory.
Adak, Sanjoy; Moore, Bradley S.
(, Natural Product Reports)
null
(Ed.)
Covering: Up to December 2020 Enzymatic halogenation reactions are essential for the production of thousands of halogenated natural products. However, in recent years, scientists discovered several halogenases that transiently incorporate halogen atoms in intermediate biosynthetic molecules to activate them for further chemical reactions such as cyclopropanation, terminal alkyne formation, C-/O-alkylation, biaryl coupling, and C–C rearrangements. In each case, the halogen atom is lost in the course of biosynthesis to the final product and is hence termed “cryptic”. In this review, we provide an overview of our current knowledge of cryptic halogenation reactions in natural product biosynthesis.
Pathak, Pravin; Zarandi, Mohammad Amin; Zhou, Xiao; Jayawickramarajah, Janarthanan
(, Frontiers in Chemistry)
With potential applications in materials and especially in light-responsive biomedicine that targets cancer tissue selectively, much research has focused on developing covalent conjugation techniques to tether porphyrinoid units to various biomacromolecules. This review details the key synthetic approaches that have been employed in the recent decades to conjugate porphyrinoids with oligonucleotides and peptides/proteins. In addition, we provide succinct discussions on the subsequent applications of such hybrid systems and also give a brief overview of the rapidly progressing field of porphyrin-antibody conjugates. Since nucleic acid and peptide systems vary in structure, connectivity, functional group availability and placement, as well as stability and solubility, tailored synthetic approaches are needed for conjugating to each of these biomacromolecule types. In terms of tethering to ONs, porphyrins are typically attached by employing bioorthogonal chemistry (e.g., using phosphoramidites) that drive solid-phase ON synthesis or by conducting post-synthesis modifications and subsequent reactions (such as amide couplings, hydrazide-carbonyl reactions, and click chemistry). In contrast, peptides and proteins are typically conjugated to porphyrinoids using their native functional groups, especially the thiol and amine side chains. However, bioorthogonal reactions (e.g., Staudinger ligations, and copper or strain promoted alkyne-azide cycloadditions) that utilize de novo introduced functional groups onto peptides/proteins have seen vigorous development, especially for site-specific peptide-porphyrin tethering. While the ON-porphyrin conjugates have largely been explored for programmed nanostructure self-assembly and artificial light-harvesting applications, there are some reports of ON-porphyrin systems targeting clinically translational applications (e.g., antimicrobial biomaterials and site-specific nucleic acid cleavage). Conjugates of porphyrins with proteinaceous moieties, on the other hand, have been predominantly used for therapeutic and diagnostic applications (especially in photodynamic therapy, photodynamic antimicrobial chemotherapy, and photothermal therapy). The advancement of the field of porphyrinoid-bioconjugation chemistry from basic academic research to more clinically targeted applications require continuous fine-tuning in terms of synthetic strategies and hence there will continue to be much exciting work on porphyrinoid-biomacromolecule conjugation.
In this Special Issue, “Featured Papers in Organometallic Chemistry”, we report on the synthesis and characterization of [IPr#–PEPPSI], a new, well-defined, highly hindered Pd(II)–NHC precatalyst for cross-coupling reactions. This catalyst was commercialized in collaboration with MilliporeSigma, Burlington, ON, Canada (no. 925489) to provide academic and industrial researchers with broad access to reaction screening and optimization. The broad activity of [IPr#–PEPPSI] in cross-coupling reactions in a range of bond activations with C–N, C–O, C–Cl, C–Br, C–S and C–H cleavage is presented. A comprehensive evaluation of the steric and electronic properties is provided. Easy access to the [IPr#–PEPPSI] class of precatalysts based on modular pyridine ligands, together with the steric impact of the IPr# peralkylation framework, will facilitate the implementation of well-defined, air- and moisture-stable Pd(II)–NHC precatalysts in chemistry research.
Olson, Rebecca A.; Korpusik, Angie B.; Sumerlin, Brent S.
(, Chemical Science)
null
(Ed.)
Photochemistry has revolutionized the field of polymer–biomacromolecule conjugation. Ligation reactions necessitate biologically benign conditions, and photons have a significant energy advantage over what is available thermally at ambient temperature, allowing for rapid and unique reactivity. Photochemical reactions also afford many degrees of control, specifically, spatio-temporal control, light source tunability, and increased oxygen tolerance. Light-initiated polymerizations, in particular photo-atom-transfer radical polymerization (photo-ATRP) and photoinduced electron/energy transfer reversible addition–fragmentation chain transfer polymerization (PET-RAFT), have been used for grafting from proteins, DNA, and cells. Additionally, the spatio-temporal control inherent to light-mediated chemistry has been utilized for grafting biomolecules to hydrogel networks for many applications, such as 3-D cell culture. While photopolymerization has clear advantages, there are factors that require careful consideration in order to obtain optimal control. These factors include the photocatalyst system, light intensity, and wavelength. This Perspective aims to discuss recent advances of photochemistry for polymer biomacromolecule conjugation and potential considerations while tailoring these systems.
Ramos de Dios, Stephany, Tiwari, Virendra K., McCune, Christopher D., Dhokale, Ranjeet A., and Berkowitz, David B. Biomacromolecule-Assisted Screening for Reaction Discovery and Catalyst Optimization. Retrieved from https://par.nsf.gov/biblio/10342651. Chemical reviews 121. Web. doi:10.1021/acs.chemrev.2c00213.
Ramos de Dios, Stephany, Tiwari, Virendra K., McCune, Christopher D., Dhokale, Ranjeet A., & Berkowitz, David B. Biomacromolecule-Assisted Screening for Reaction Discovery and Catalyst Optimization. Chemical reviews, 121 (). Retrieved from https://par.nsf.gov/biblio/10342651. https://doi.org/10.1021/acs.chemrev.2c00213
Ramos de Dios, Stephany, Tiwari, Virendra K., McCune, Christopher D., Dhokale, Ranjeet A., and Berkowitz, David B.
"Biomacromolecule-Assisted Screening for Reaction Discovery and Catalyst Optimization". Chemical reviews 121 (). Country unknown/Code not available. https://doi.org/10.1021/acs.chemrev.2c00213.https://par.nsf.gov/biblio/10342651.
@article{osti_10342651,
place = {Country unknown/Code not available},
title = {Biomacromolecule-Assisted Screening for Reaction Discovery and Catalyst Optimization},
url = {https://par.nsf.gov/biblio/10342651},
DOI = {10.1021/acs.chemrev.2c00213},
abstractNote = {Reaction discovery and catalyst screening lie at the heart of synthetic organic chemistry. And while there are efforts at de novo catalyst design using computation/artificial intelligence; at its core, synthetic chemistry is an experimental science. This review overviews biomacromolecule-assisted screening methods and the follow-on elaboration of chemistry so discovered. All three types of biomacromolecules discussed–enzymes, antibodies, and nucleic acids–have been used as ‘sensors’ to provide a readout on product chirality exploiting their native chirality. Enzymatic sensing methods yield both UV-spectrophotometric and visible, colorimetric readouts. Antibody sensors provide direct fluorescent readout upon analyte binding in some cases, or provide for cat-ELISA (Enzyme-Linked ImmunoSorbent Assay)-type readouts. DNA biomacromolecule-assisted screening allows for templation to facilitate reaction discovery, driving bimolecular reactions into a pseudo-unimolecular format. Also, the ability to use DNA-encoded libraries permits the barcoding of reactants. All three types of biomacromolecule-based screens afford high sensitivity and selectivity. Among the chemical transformations discovered by enzymatic screening methods are the first Ni(0)-mediated asymmetric allylic amination, and a new thiocyanopalladation/carbocyclization transformation in which both C-SCN and C-C bonds are fashioned sequentially. Cat-ELISA screening has identified new classes of sydnone-alkyne cycloadditions and DNA-encoded screening has been exploited to uncover interesting oxidative Pd-mediated amido-alkyne/alkene coupling reactions.},
journal = {Chemical reviews},
volume = {121},
author = {Ramos de Dios, Stephany and Tiwari, Virendra K. and McCune, Christopher D. and Dhokale, Ranjeet A. and Berkowitz, David B.},
editor = {Sharon Hammes-Schiffer, Editor-In-Chief
Ruma Banerjee}
}
Warning: Leaving National Science Foundation Website
You are now leaving the National Science Foundation website to go to a non-government website.
Website:
NSF takes no responsibility for and exercises no control over the views expressed or the accuracy of
the information contained on this site. Also be aware that NSF's privacy policy does not apply to this site.
An official website of the United States government
