Science: modified hemoglobin can be used to catalyze high strain carbon ring compounds

In cyclic organic molecules, the cyclic strain is determined by the ratio of bond length to bond length and the steric hindrance effect of non bond substituents The simplest carbon rings, cyclopropane and cyclobutane, have a ring strain of 26-28 kcal / mol The introduction of carbon carbon multiple bond or bridge bond into these small ring systems will cause additional strain and structural rigidity For example, cyclopropene with inner ring double bond has a ring strain of 54 kcal / mol, while bicyclic [1.1.0] butane has a ring strain of 66 kcal / mol These carbon rings have special attraction as intermediates in chemical synthesis, because they can be transformed into special compounds through strain release; in the field of supramolecular materials, the carbon ring structure with high ring strain gives rare structural rigidity, resulting in some interesting physical properties, such as high mechanical stability and high glass transition temperature The inherent ability of these strain structures can also be released in response to external forces, leading to fundamental changes in physical properties (such as electrical conductivity), which is a very needed feature of stimulus response materials However, the high ring strain greatly increases the difficulty of synthesis The common way to prepare dicyclobutane is to start from the substructure of dibromo-2 - (bromomethyl) cyclopropane, use organic lithium reagent to exchange lithium and halogen, and then carry out nucleophilic substitution under strict anhydrous and low temperature conditions The other way is to rely on the double conversion of carbene to alkyne, but the examples in the literature are mostly limited to methylene carbene The synthesis of asymmetric bicyclobutane is very challenging, and it can produce many chiral centers at the same time Transition metal chiral catalysts based on rhodium, iridium and cobalt are needed to synthesize cyclopropene by adding enantioselective carbene to alkynes The development of a highly efficient and selective sustainable catalytic system under mild conditions will be a significant progress in the synthesis of high strain carbon rings The enzyme for the formation of dicyclobutane catalyzed by hemoglobin (source: Science) is a biological catalyst, which can accelerate the chemical conversion to several orders of magnitude, and show the precise control of selectivity Although various products containing cyclopropane have been synthesized in nature, cyclopropene or bicyclobutane fragments are rare This may be due to the poor stability of these structures under separation / purification conditions leading to their decomposition Nevertheless, the researchers envisage that the activity and selectivity of these enzymes can be optimized through directed evolution, and the existing enzymes can be reused to catalyze the synthesis of high strain carbon ring compounds A research team led by Professor Frances h Arnold from California Institute of technology has designed an enzyme that has taken a big step in catalyzing the synthesis of high strain carbon ring compounds (DOI: 10.1126 / science Aar4239) After the enzyme used to catalyze cyclopropanization has been manufactured, researchers can use this new biocatalyst to prepare cyclopropene or bicyclobutane by reacting one or two carbones with carbon carbon triple bond, which is not found in nature The range of formation and derivation of bicyclobutane (source: Science) Professor Arnold's team used a hemoglobin, a metal enzyme with a central iron porphyrin complex In humans and other mammals, hemoglobin can help transfer oxygen from the lungs to tissues throughout the body By directed evolution, the amino acid residues around the active sites of proteins were changed until they found a variant with excellent reaction performance Evolutionary proteins can even react in a chiral way: cyclopropene is produced almost entirely in the form of a single enantiomer, and dicyclobutane reaction first produces exo endo rings Cyclopropene can be used as a structural unit, a precursor of biorthogonal imaging and a monomer in polymer synthesis Large scale production of cyclopropene by new evolutionary proteins can facilitate researchers to further explore its potential utility in different fields By activating the C-C bond, the evolutionary protein can make the alkyne added, stabilize the reactivity of cyclopropene intermediate (the formation of dicyclobutane) and precisely control the stereoscopic transfer process of carbon and alkene, thus realizing the required transformation The biocatalytic reaction of evolutionary proteins has a surprisingly wide range of substrates, as well as high reactivity and selectivity, providing a route for large-scale preparation of more than 25 products This kind of biocatalysis system can easily synthesize the rare multifunctional molecular structure in nature and expand a series of chemical structures of biological system Corresponding author: Professor Frances h Arnold first author: Kai Chen