Methylation makes magic as in life:

https://www.sciencemag.org/news/2020/03/newly-discovered-magic-methyl-reaction-could-tu...

"For years, drug discovery chemists have struggled to streamline a process that can boost a drug’s potency up to 2000-fold: “magic methylation.” The reaction sweeps out single hydrogen atoms and replaces them with methyl groups—reshaping the drug molecule to more easily interact with its biological targets. But carrying out this sleight of hand is so difficult that few researchers even try. Now, a team of chemists reports it has created a new catalyst that performs this delicate exchange with ease on a wide variety of druglike molecules, an advance that could lead to novel treatments for everything from cancer to infectious diseases.

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"Nature builds and reshapes molecules “in a totally different way,” White says. Chemical changes are made using large, complex enzymes that grasp hydrocarbon scaffolds so that just one C-H bond nuzzles up to the enzyme’s catalytic site—the point at which a reaction takes place. However, each enzyme typically works with only one specific molecule. “If I want to work on a different molecule, I need a new enzyme,” White says. “We want [a reagent that is] just as selective, but general.”

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"In 2015, she and her colleagues devised a set of conditions that allowed the iron catalyst and a variant to add oxygen atoms to druglike molecules. And in 2019, they created a similar manganese-based catalyst that performed the oxygen-for-hydrogen swap on druglike molecules containing nitrogen and other common add-ons.

"But that was just the first step. Now, White’s team reports it has come up with chemical additives that help this latest catalyst complete the “magic methyl” process. After replacing a hydrogen with an oxygen, it steals a methyl group from a reagent known as trimethylaluminum and inserts it in oxygen’s place. White’s team carried out this molecular surgery on 41 different hydrocarbons, including 16 common druglike scaffolds, the researchers report today in Nature.

"The upshot, White says, is that this reagent will now make it simple and cheap for drug hunters to insert “magic methyl” groups into their molecules. “We hope a lot more drugs with the magic methyl effect will be discovered,” White says."

Comment: Nature always teaches us. Methylation is magical .