In their 2014 Journal of the American Chemical Society paper, Li, Liskey, and Hartwig report on a nickel-catalyzed method for the borylation of aryl halides using diboron reagents. This process enables efficient and selective C–B bond formation in a range of aryl halides.

In their 2019 Journal of the American Chemical Society paper, Karmel, Chen, and Hartwig introduce a method for the palladium-catalyzed hydroamination of alkenes using ammonia, which provides a direct route for creating primary alkylamines.

In their 2015 Journal of the American Chemical Society paper, Cheng and Hartwig present a selective iridium-catalyzed method for the intramolecular borylation of aliphatic C–H bonds. This technique enables precise C–B bond formation on unactivated aliphatic carbon centers, achieving high selectivity without pre-functionalized substrates.

In their 2020 Journal of the American Chemical Society paper, Jones, Fast, and Schley report on a novel cobalt-catalyzed method for C–H activation and hydroarylation of alkenes. This reaction provides an efficient route for forming C–C bonds, enabling the hydroarylation of alkenes with high selectivity and under mild conditions.

In their 2012 Journal of the American Chemical Society paper, Ohmura, Torigoe, and Suginome describe a selective, nickel-catalyzed borylation of C(sp^3)–H bonds in aliphatic amines. This approach allows direct borylation of primary and secondary C–H bonds adjacent to nitrogen, creating versatile organoboron intermediates with high selectivity.

In their 2014 Chem. Communications paper, Ohmura, Torigoe, and Suginome introduce a novel method for site-selective borylation of aromatic compounds using a copper catalyst. This approach achieves high regioselectivity for C–H borylation, enabling selective functionalization of specific positions on aromatic rings, particularly useful in synthesizing complex organic molecules.

In this 2006 study, Murphy, Lawrence, Kawamura, Incarvito, and Hartwig report the development of a highly efficient and selective method for hydroamination of olefins using a platinum catalyst. The platinum complex effectively catalyzed C–N bond formation across a range of substrates under mild conditions.

In the 2000 paper by H. Chen, S. Schlecht, T. C. Semple, and J. F. Hartwig, published in Science, the authors present a pioneering study on the use of palladium catalysts for the direct amination of aryl halides. This work was groundbreaking as it demonstrated a highly efficient method for forming C–N bonds directly from aryl halides and amines.

J. F. Hartwig's 2016 paper covers key developments in transition metal-catalyzed processes that facilitate the direct functionalization of C–H bonds, often viewed as inert and difficult to modify selectively. Hartwig explores various catalytic systems, including palladium, iridium, and ruthenium catalysts, which have enabled efficient C–H activation under mild conditions, allowing for more sustainable approaches in synthesis by minimizing reliance on pre-functionalized starting materials.

The paper describes direct addition of amines to alkenes.

Hartwig describes a novel palladium-catalyzed method for C–H borylation of aromatic heterocycles.

Liskey and Hartwig present a highly selective, iridium-catalyzed borylation for aliphatic C–H bonds under mild conditions.

The authors present a novel iridium-catalyzed borylation method for aryl C–H bonds, allowing direct functionalization of unactivated arenes.

The authors demonstrate a palladium-catalyzed method for the amination of aromatic C–H bonds, enabling direct incorporation of nitrogen.

The paper discusses mechanistic insights and strategies that have broadened applications for C–H activation in synthetic organic chemistry.

The authors present a detailed computational and experimental study on the mechanistic pathways of iridium-catalyzed borylation of C–H bonds.

The authors introduce a photoredox-catalyzed cross-coupling reaction enabling the formation of C–C bonds without traditional organometallic reagents.

The authors explore the mechanisms of selective C–H activation catalysis involving transition metals through detailed computational studies.

This paper presents a novel catalytic approach for highly selective C–H borylation of arenes, employing a chromium complex.

This paper introduces a new approach to enantioselective C–H functionalization using engineered palladium catalysts.

This review discusses innovative approaches to C–H activation, focusing on mechanisms to break strong C–H bonds selectively.

https://phys.org/news/2020-10-approach-chemistry-enables-boron-added.html

Researchers have developed a new method to add boron atoms to organic molecules using light-driven chemistry, eliminating the need for transition metals. This approach is expected to simplify synthesis processes and reduce environmental impact by making boron addition more accessible and eco-friendly.

https://cen.acs.org/synthesis/c-h-activation/Alkane-borylation-reaction-kicks-metals/98/i42

Researchers have developed a novel alkane borylation reaction that bypasses the need for transition metal catalysts, traditionally essential in such reactions. This approach utilizes photoredox chemistry to enable borylation with milder conditions and reduced environmental impact, making the process greener and more sustainable. The reaction opens new possibilities for functionalizing hydrocarbons in pharmaceutical and material science applications by avoiding the cost and toxicity associated with metal catalysts.

https://news.berkeley.edu/2020/05/21/scientists-finally-crack-natures-most-common-chemical-bond/ Scientists finally crack nature’s most common chemical bond

https://phys.org/news/2023-12-catalyst-electronically-ch-functionalization.html

The Chirik Lab at Princeton has developed a cobalt-based catalyst that enables electronically controlled C–H functionalization, allowing for precise borylation in fluoroarenes without the need for directing groups. The catalyst offers potential applications in pharmaceutical and materials synthesis by expanding the toolkit for site-selective modifications.

2.5 M butyl lithium was added to a solution of furan at -78 deg Celsius under inert atmosphere. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was cooled to -78 deg Celsius and 43 was added. Then NBS was added. The reaction was warmed to room temperature and 10 mL of water was added. Extraction with ethyl acetate and followed by vacuum evaporation afforded a residue. This was purified by silica gel column chromatography to give 48 as a colorless oil.

Copper-Catalyzed Oxidation: To a premixed 2.0 M NaOH and 30% hydrogen peroxide and 15 was added in THF at 0 deg Celsius. The mixture was stirred at room temperature for 11 hours. 1.0 M aqueous hydrochloric acid was added and reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine. Volatiles were evaporated with rotary evaporator and the residue was purified by silica gel column chromatography. 45 was obtained as a yellow solid.

Suzuki Coupling Reaction: 15, boronic acid, potassium phosphate, Pd(dppf)Cl2 and dioxane were added to a vial in a glove box. Then, the vial was removed from the glove box and water was added. The reaction mixture was heated to 100 deg Celsius for 2.5 hours. Volatiles were rotary evaporated and the residue was purified by silica gel column chromatography to give 37 as a colorless oil.

Deboronation and Deuterium Exchange: To a reaction vial, 15, [Ir(cod)OMe]2 and THF were added. The vial was sealed, removed out of the dry box and D2O was syringed. The reaction mixture was heated to 80 deg Celsius for ~3 h. The volatiles were removed by rotary evaporator and the residue was purified by column chromatography. 39 was obtained as a colorless oil.

To a reaction vial, cyclopropane carboxylate, B2Pin2, 6.3 micromol of [Ir(cod)(OMe)]2, 2-mphen and cyclooctane (solvent) were added. The reaction mixture was heated at 100 degrees Celsius for 20 h. The product mixture was purified by silica gel column chromatography. CH2Br2 was added as the internal standard and the product was characetrized by H-NMR spectroscopy

Diisopropylbenzene, B2PIn2, [Ir(cod)(OMe)]2, 2.5 mg of 2-mphen and cyclooctane were added to a reaction vial. The reaction mixture was heated to 100 deg Celsius, cooled and then stirred for 20 h under inert atmosphere. The reaction progress was monitored with GC-MS. Crude product was purified by silica gel column chromatography.

Metallophotoredox Reaction: In a glove-box, 4,4’-di-tert-butyl-2-2`-bipyridine and NiCl2.DME were added to a reaction vial, followed by addition of THF. The mixture was heated on a heating plate for 10 min. The vial was taken back into the glove-box, and the volatile materials were removed, followed by addition of Ir[dFCF3ppy]2(bpy)PF6, 4-bromobenzonitrile, Cs2CO3, potassium triflluoroborate and dioxane. The vial was capped and stirred under irridation of a 34 W blue LED lamp for 48 h. The crude reaction mixture was extracted with ethyl acetate. The resulting solution was concentrated under reduced pressure, and the residue was purified by column chromatography to give the product 52 as a colorless oil.

0.250 mol of the substrate, 3 equivalents of B2Pin2, 6.3 micromol of [Ir(cod)(OMe)]2, 13 micromol of 2-mphen and 200 microliter of cycloctane were added to a vial. The reaction mixture was heated to 100 degrees Celsius for 20 hours. Product was purified by column chromatography and characterized by proton NMR spectroscopy.

Carbocycles underwent borylation at the most accessible bond which is the bond with least steric hindrance. The secondary C-H bond was found to undergo borylation.

Heat was applied outside of dry box in this procedure. Then, the reaction vial is taken back into the glove box for further manipulations.

To a vial, an alcohol of interest was added inside a dry box. This was followed by 1.3 equivalents of HBPin and stirred for ~ 10 minutes to convert the alcohol to the borate ester. The vial was fitted with a cap and heated to 100 degrees Celsius outside the dry box. The vial was cooled and then 2.5 mol % of [Ir(cod)(OMe)]2, B2Pin2 and cyclooctane (solvent) were added under inert conditions. Heated to 80 degree Celsius (outside dry box) to activate the catalyst. Cooled to room temperature and charged with remaining B2Pin2 and more cyclooctane under inert conditions. Reaction mixture was stirred for 20 hours. CH2Br2 was added as an internal standard. Product was analyzed by proton NMR spectroscopy.

In a nitrogen filled glove box, a vial was charged with (MsSH)IrBPin3, a ligand, B2Pin2 (bis-pinacolatodiboron) and THF. Ligands are phenanthroline derived. Dodecane was used as the internal standard. The reaction vial was sealed with a Teflon cap. The mixture was heated to 100 degrees Celsius. Reaction was monitored by GC.

The same reaction was repeated replacing THF with diethyl ether.

The ligands used are 2-methylphananthroline (mphen), 2,9-dimethylphenanthroline (2,9-dmphen) and 3,4,7,8-tetramethylphanathroline (tmphen).

positively charged reactive intermediate in a reaction, with carbon atom with only six valence electrons in its valence shell

Borylations of heterocycles occured at C-H bonds closer to the heteroatom.

Acyl groups attached to the nitrogen atom are derived from non-aromatic carbon chains

Although several studies were carried out, the exact reason for the high reactivity of m-phen ligand is unclear. However, it can be concluded that the change in the methyl goup leads to the higher activity of the catalyst in borylation.

Borylation of primary C-H bond is irreversible leading to exclusivity in the product formed.

Borylation enabled placement of bromine atom at the strogest C-H bond instead of the weaker C-H bond that is typically observed.

Exclusive borylation occurred at the position beta to nitrogen.

Reaction preferentially occurred at the equatorial C-H over the axial C-H bond because reaction at the equatorial C-H bond is irreversible whereas the reaction at the axial C-H bond occurs but is reversible.

Less reactive carbocycles also underwent borylation because of the high reactivity of mphen.

Primary, secondary and tertiary alcohols were borylated at primary C-H bonds. However, this occurred after initial borylation of the hydroxyl group.

Alkyl arenes underwent borylation forming a single product or a mixture of products depending on the substitution pattern, ortho, meta or para.

No borylation takes place at the hindered geminal dimethyl groups.

Monoborylation took place at the n-butyl group and not at the more hindered t-butyl group.

Several functional groups that containied methyl groups underwent borylation at the primary C-H bonds. Once again, the specificity of the C-H bonds was proven.

When the borylation reaction was conducted with pentylcyclohexane with only one set of primary C-H bonds, only these bonds reacted. This shows the high specificity of the catalyst [Ir(OMe)(COD)]2 and 2-mphen for the primary C-H bonds.

When reactions were performed in solvents such as cyclohexane and cyclooctane, it was found that borylation occurred on the substrate rather than on cyclohexane or cyclooctane. Between cyclohexane and cyclooctane, cyclooctane was more inert towards borylation. Therefore, all reactions were conducted in cyclooctane as the solvent.

When the ligand is 2-methylphenanthroline, the catalyst is way more reactive than when coordinated by other ligands and shows selectivity for primary C-H bonds.

Borylations carried out in the presence of iridium catalysts are selective for primary C-H bonds in a wide range of substrates.

In a glove box under inert atmosphere, catalyst [Ir[Cod][OMe]2], 2-mphen and B2Pin2 were added. A suitable alkane (substrate) and cyclooctanol (solvent) were added and the vial sealed with a Teflon cap. Reaction was heated for 100 degrees Celsius for 20 hours. The reaction was cooled. Product was isolated and purified by column chromatography. Product was analyzed by proton NMR spectroscopy.

a free radical mechanism by which bromine is introduced under conditions of heat or light

A C-H bond located on a carbon directly attached to a benzene ring

a carbon atom that has four different groups connected to it

a carbon atom that is connected to three other carbon atoms and a hydrogen atom

a -CH2 carbon

Usually involves a photoredox catalyst, a transition metal catalyst, visible or UV light source and polar aprotic solvents.

These conditions are palladium catalysts, strong bases, polar aprotic solvents and elevated temperatures.

A reaction that extends the carbon chain of a molecule

A reaction that introduces a vinyl group into a molecule

A chemical reaction where aryl group is introduced in a molecule

A reaction that introduces halogen(s) into a molecule

A reaction that introduces an amino group into a molecule

A reaction that involves loss of electrons

A carbon-hydrogen bond in a cyclohexane ring that is parallel to the ring axis, pointing straight up or down.

A reaction that preferentially forms a diastereomer over others

Derived from ammonia, in which one or more hydrogen atoms are replaced by alkyl or acyl groups

An organic compound formed by the reaction of an alcohol with carbamic acid

saturated hydrocarbon with a straight chain structure

A chemical reaction in which a single reactant is simultaneously oxidized and reduced, forming two different products with distinct oxidation states.

Chemical groups where an alkyl chain is attached to a boronate functional group

A chemical reaction in which the reaction rate is directly proportional to the concentration of a single reactant.

cycloalkane with eight carbons

cycloalkane with six carbons

saturated hydrocarbons with carbon atoms arranged in a ring structure

A linear alkane hydrocarbon with 12 carbon atoms

A solvent that does not react with any reactant or product and functions only as medium for the reaction to occur.

Refers to a location on a molecule that is farthest from a reference point

A molecule that binds to a central metal atom, by donating one or more electrons through coordinate covalent bonds

Two positions away from the reference point

cyclic compounds consisting of carbon atoms

specific group of atoms in an organic compound that are responsible for the compound's physical and chemical properties

an organic compound where boron is bonded to two alkoxy groups.

Hindrance to movement and/or chemical reaction of a molecule due to the position of bulky groups

A reactive neutral intermediate

omega position refers to the terminal position, the farthest position from the reference point.

An atom or a functional group that withdraws electron density from the rest of the molecule.

Restriction to movement or a chemical reaction caused by spatial arrangement of bulky groups.

An organic compound when two equivalents of alcohol reacts with an aldehyde

An organic compound where two carbonyl groups are bonded to a single nitrogen atom.

A five membered aromatic heterocycle

A C-H bond located on the benzene ring, at a position that is two carbons away from a reference substituent.

An aromatic compound consisting of a benzene ring with two isopropyl groups at 1 and 4 positions.

Aromatic compounds in which one or more hydrogen atoms are replaced by alkyl groups.

An organic compound formed when a ketone reacts with two equivalents of an alcohol.

A reactive species formed by removing one hydrogen atom from an alkane

Position of a carbon atom adjacent to a heteroatom

Negatively charged hydrogen atom

Biological catalyst

A chemical substance that speeds up a reaction.

A functional group derived from an aromatic ring

A hydrogen atom attached to a secondary carbon, which is a carbon connected to two other carbon atoms. A hydrogen atom attached to a tertiary carbon, which is a carbon connected to three other carbon atoms.

A hydrogen atom attached to a primary carbon, which is a carbon connected to only one other carbon.

Position of a carbon atom that is adjacent to a carbon-carbon double bond

Position of a carbon atom that is directly attached to a benzene ring

An atom in an organic molecule other than carbon and hydrogen

A reactant that is first completely consumed in a reaction, thereby, limiting the amount of product formed.

A term used to describe the attachment of a ligand to a metal center.

The component present in larger amount and serves as the medium for the chemical reaction to occur.

A compound that undergoes a chemical reaction.

A chemical reaction that involves the introduction of a boron containing group into an organic molecule.

Professor Arnold's team demonstrates the first enzyme catalyzed carbenoid insertion into N-H bonds. The reaction proceeds in water with moderate yield.

This paper shows how directed evolution can be used to modify existing enzymes to carry out synthetically useful reactions. P450 BM3 enzymes were engineered to catalyze cyclopropanation of styrenes with very high diastereoselectivity and enantioselectivity.

Bornscheuer discusses the various applications of biocatalysis. Biocatalysts offer a more practical and a green route to synthesis when compared to organometallic catalysts. Professor Arnold's work features the use of biocatalysis as a key step in C-Si bond formation.

This paper describes how Cu(OTf)2 can be used to catalyze asymmetric carbenoid insertion into a Si-H bond. 22 reactions were run and the product, alpha-silyl esters, was formed in high yields and up to 99% enantiomeric excess. When Professor Arnold's group ran the desired reaction with Cu(OTf)2, a complex mixture of products from Si-H, O-H and N-H insertion reactions was observed.

This paper discusses the use of rhodium catalysts in the asymmetric, intramolecular silylation reaction of cyclopropyl C-H bonds. The reaction proceeds with high enantiomeric excess. However, when Professor Arnold's group used Rh2(OAc)4 to catalyze C-Si bond formation, they observed that O-H and N-H insertions often dominated over the preferred silylation reactions.

Silicon, an isostere of carbon, has unique properties. Properties of silicon and application of organosilicon molecules in drug release technology, etc., are discussed. These properties can be used to enhance drug potency and improve pharmacological action.

Reactions catalyzed by Rma cyt c have distinct advantages such as high chemoselectivity and enantiospecificity over reactions catalyzed by organometallic catalysts.

Free alcohols and primary amines are reactive functional groups that do not interfere with this enzymatic carbene-transfer reaction.

Rma cyt c exhibits preference for carbon-silicon bond formation over other competing side reactions.

M100 is the specific amino acid residue within the protein sequence that has been identified to be critical for the protein’s function. it is very important to determine the ideal amino acid residue for this position. Site saturation mutagenesis is employed.<br> Site-saturation mutagenesis is a form of random mutagenesis, allowing the substitution of a specific amino acid site with one of 20 possible amino acids in a single experiment. In this study, this technique is employed to generate a series of enzymes with enhanced activity and enantiospecificity.

The amino acid, histidine

The wild-type protein chosen must exhibit some degree of activity for the desired reaction. When compared to hemin, hemin with bovine serum, a range of cytochrome P450 and myoglobin variants, it was found that Rma cyt c showed 97% ee. This was chosen as the enzyme that would form the starting point for directed evolution.

Natural variant of cytochrome c protein from the natural variant Rhodothermus marinus.

Heme proteins that were readily available were screened to identify the one that gave the highest enantioselectivity. This served as a starting point for directed evolution. Purified heme protein, silane, diazo ester, thiosulfate, methyl cyanide and M9-N buffer as the medium for microbial growth were stirred at room temperature in anaerobic conditions. Reactions were performed in triplicate. Unreacted starting material was obtained in all cases and no further purification was carried out.

The sequence of nucleotides that is translated into proteins

Elements that have the same number of electrons in the outermost shell (also known as valence shell) and have similar electronic properties. For example, carbon and silicon are isosteres as they both have four valence electrons.

The turnover number of an enzyme, is the number of substrate molecules converted into product by an enzyme molecule in a unit time when the enzyme is fully saturated with substrate.

IA method of engineering proteins towards a defined property. Process of directed evolution: Directed evolution mimics "real" evolution and is accelerated in the laboratory by focusing on individual genes expressed in fast‐growing microorganisms such as E. coli. Enzyme chosen (known as wild-type) must show at least a minimal desired reactivity. Mutations are randomly or site specifically introduced to the gene of the wild type protein. Then, the library of protein variants is screened for the ones with enhanced reactivity. The improved enzymes are used as parents for the next round of mutation and screening. Additional beneficial mutations are introduced if needed. This can continue for several cycles until a desired and new property of the enzyme is attained.

Carbene is a neutral reactive intermediate; a carbene insertion reaction is the insertion of a carbene into a chemical bond.

conditions that occur in the natural host organism in contrast to laboratory conditions

The study shows the loss of axial methionine from cyt c. The same phenomenon was observed over a range of cyt orthologs. In Professor Arnold's work, the labile nature of methionine in cyt c is believed to be responsible for the improved efficacy of the C-Si bond forming biocatalyst.

This paper discusses the directed evolution via mutation of the amino acids of myoglobin that lead to 49% enantiomeric excess. Engineered myoglobin catalysts are used to synthesize thioethers via a carbene S-H insertion reaction. Conversions as high as 99% and turnover numbers as high as 5400 were observed.

O'Brien and Herschlag discuss the evolution of a superfamily of enzymes and the diverse reactions they catalyze. Single point mutations can lead to the evolution of new enzymatic activities. Professor Arnold's work also involves mutations of the WT to alter the reactivity of the enzyme.

A new approach to conducting chemical reactions in which reactants must react rapidly and selectively with each other under physiological conditions. Two key and relevant features of bioorthogonal reactions are high selectivity and compatibility with naturally occurring functional groups.

Metabolic engineering is the production of specific target chemicals in high yield and stereoselectivity by altering the metabolic pathways. Metabolic pathways are changed via recombinant DNA technology.

Although transition metal catalysis offers several advantages, the metals typically used are toxic. Removal of these metals after the synthetic process is time consuming and expensive. The process described in the research ensures sustainability and reduces cost.

Functional group protection and deprotection increases the number of steps and auxiliary agents during synthesis and is not considered green. The methodology described in this research obeys one of the principles of green chemistry: "Unnecessary derivatization (use of blocking groups, protection/deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste."

Rma cyt c V75T M100D M103E shows excellent enantioselectivity and turnover over a wide range of substrates. Silicon substrates with weakly electron-donating or -activating methyl substituents (4), strongly electron donating -OMe (5), weakly deactivating -Cl (6), strongly deactivating -CF3 (7), and moderately deactivating COOMe and CONMe (9 and 10 respectively) show moderate to excellent turnover and high selectivity. No direct relationship exists between turnover number and substituent effects from this study. Enantioselectivity is excellent in all substrates. All products were identified using GC-MS, and no traditional organic chemistry techniques were used.

Additional diazo compounds that were successful were R3 = -CH3, -CH2CH3, -Ph.

aromatic compounds in which one or more ring carbon atoms are replaced by a heteroatom such as nitrogen, sulfur or oxygen.

organic compounds that contain a -CONH2 structural feature

organic compounds that contain a -COOR functional group

organic compounds that contain a halogen connected to an alkyl group such as methyl, ethyl, etc.

organic compounds that contain a C-O-C structural feature

General method for the preparation of phenyl dimethyl silanes: In a 100 mL round bottom flask, chlorodimethylsilane in THF was cooled to zero degrees. A solution of the appropriate Grignard reagent was added dropwise over ~15 minutes. The reaction was allowed to reach room temperature and stirred for ~8 hours. The product mixture was quenched with ammonium chloride solution. The product was extracted into ether and then isolated. Purification was done by column chromatography.

Via site-saturation mutagenesis, V75 and M103 positions along the protein sequence were identified as likely beneficial mutations and were randomized, i.e., the amino acids at these positions are replaced by random ones. A large number of random variants, which together constitute a library, are produced and then screened in an attempt to discover a highly active variant among them. The evolved triple mutant fits the bill.

Recombinant protein is a protein encoded by a gene that has been cloned in a system that supports expression of the gene (in this case, it is M100). Modification of the gene by recombinant DNA technology can lead to expression of a mutant protein. In this study, M100D mutation is more highly activating than the wild-type protein.

oxygen-free conditions

At the theoretical level, the steps needed for obtaining a recombinant protein are straightforward. Take your gene of interest, clone it, transform it into the host of choice (here it is E. coli), induce, and then the protein is ready for purification and characterization.

located at a farther distance

cells with membrane-bound organelles

Turnover frequency for each variant relative to wild-type protein: WT: 1 M100D 2.8 +/- 0.2 V75T M100D 4.6 +/- 0.3 V75T M100D M103E 7.1 +/- 0.4

From this experimental data, it is clear that directed evolution has resulted from changing the enzyme from unselective wild-type into a highly enantioselective variant.

Experiments were conducted with purified heme protein, silane, diazo ester, sodium dithionate, MeCN, and M9-N buffer at room temperature in anaerobic conditions for 1.5 h. Three trials were conducted. Turnover number reported is the average of the three trials. Unreacted reactants were not isolated.

Axial methionine in cyt c is known to be labile. The proposed model for the binding for the iron-silane complex is one where the complex forms such that the silane molecule takes the place of the axial methionine. The silane may approach from the more exposed side in the protein. This further explains the observed stereochemistry of the organosilicon product. The V75T, M100D, and M103E mutations are thought to improve reactivity by providing better access of the substrate to the iron center.

In this study, Professor Arnold's group used protein-engineered variants of cytochrome P450 BM3 to bring about highly diastereoselective and enantioselective cyclopropanation reaction of styrenes from diazoester. Variant BM3-CIS was identified as a competent cyclopropanation catalyst. It exhibits a strong preference for the cis product and forms both diastereomers over 90% ee and is as stable as the wild-type enzyme. P450 BM3 works on a wide range of substrates with both electron-donating and electron-withdrawing substituents in styrene.

branch of biology that deals with the structure and function of nucleic acids and proteins

The preference shown by an enzyme when exposed to a competitive attack on two or more substrates or two or more positions in the same substrate.

The ability of a protein's binding site to bind to only specific ligands. The fewer ligands a protein can bind to, the greater its specificity.

Solvents that contain halogens such as fluorine, chlorine, bromine and iodine. For example, methylene chloride, CH2Cl2, is a halogenated solvent.

Certain iridium catalytic systems show 97% ee, while copper catalysts show 35% ee and rhodium has been shown to exhibit 77% ee.

gram-negative, rod-shaped bacterium

Cytochromes are proteins that contain heme as the prosthetic group.

A type of metalloprotein that contains a heme group, which is required for the functionality of the protein

AP Essential Knowledge Enduring Understanding 1.C

Iron compounds are found abundantly in nature and are cheap. The paper discusses the use of iron complexes as catalysts to add Si-H (hydrosilylation) across alkene double bonds. The catalysis proceeds with high regioselectivity, thereby eliminating the need for product purification.

The article presents a wealth of information about heme c and cytochrome c. This knowledge is essential for engineering enzymes to catalyze novel reactions.

Iron carbene complexes react with organosilanes leading to insertion of carbene in the Si-H bond. This is another example of the use of organometallic catalyst to carry out the insertion reaction.

This paper presents the crystal structure of cyt c. X-ray crystallography shows that cytochrome c consists of alpha helices wrapped around the compact heme core. In addition, there is a singular alpha helix that wraps around the back of the molecule.

AP Chemistry Science Practice 1: The student can use representations and models to communicate scientific phenomena and solve scientific problems.

AP Chemistry Science Practice 4: The student can plan and implement data collection strategies in relation to a particular scientific question.

Common Core ELA - Literacy RST 11.12.4 Determine the meaning of symbols, key terms, and other domain-specific words and phrases as they are used in a specific scientific or technical context relevant to grades

Common Core ELA Literacy RST 11.12.10 By the end of grade 12, read and comprehend science/technical texts in the grades 11-CCR text complexity band independently and proficiently.

AP Chemistry Essential Knowledge 4D: Reaction rates may be increased by the presence of a catalyst.

This paper describes how silicon isosteres can be critical to drug discovery success. Professor Arnold's paper uses an approach whose benefits can be applied to drug design.

This paper describes how potassium tert-butoxide can catalyze the silylation of C-H bonds in aromatic heterocycles. The reaction is one step, occurs under mild conditions and is scalable to ~100 g. This methodology replaces the expensive route of using Rh or Ir complexes.

equal amounts of enantiomers (mirror images) of a chiral (asymmetric) compound

Rma cyt c V75T M100D M103E variant is not the most evolved protein. This is considered only as a starting point to future enzymes that will show greater selectivity.

Enantiomeric excess was determined using chiral SFC.

Products were analyzed using gas chromatography.

With each mutation, the chemoselectivity of the enzyme is greatly enhanced. V75T M100D M103E favors the carbon-silicon bond 29 times more than the wild type. This is attributed to the improved binding and orientation of the silicon donor in the enzyme's active site.

Electrochemical analysis revealed the loss of methionine from a range of cytochrome proteins.

types of heme proteins

excess of one enantiomer over the other in a mixture of enantiomers

Heme proteins are required for the reaction to occur.

a microbial growth medium

A very large class of proteins that contain heme as the prosthetic group. Examples of heme proteins are hemoglobin, myoglobin and cytochrome c.

https://www.chemistryworld.com/news/what-is-directed-evolution-and-why-did-it-win-the-chemistry-nobel-prize/3009584.article

https://youtu.be/FWEN2pxoXoQ

https://cen.acs.org/people/nobel-prize/directed-evolution-changing-world/96/i44

Refers to the process of separating desired products from biosynthetic pathways

Any reagent that exhibits chirality (or asymmetry) in its molecular structure

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901037/

https://www.nobelprize.org/uploads/2018/10/advanced-chemistryprize-2018.pdf

A generally applicable protocol, as a result of directed evolution, over a variety of substrates illustrates the synthetic utility of the mutant.

compounds that contain two fused benzene rings; also referred to as polycyclic aromatic hydrocarbon

organic compounds that contain a halogen connected to a benzene ring