Friday , October 22 2021

From glass to 3D in minutes – ScienceDaily


In a recent study by one researcher, the UCLA / Caltech team has shown that it can produce small molecules such as hormones and medications no less than 30 minutes. It was a few hours before, and even less.

The group used technique called microelectric diffraction (MicroED), which learned the 3-D molecules, especially proteins, in the past century. In this new study, researchers have shown that this technique can be used for small molecules, and that this process takes much less time than is expected. In contrast to some of the methods, some of them are the salt grains of growing crystals – this method can work with the powder mill starting from the mill, and sometimes even boxing, as the new study shows.

"We've taken the lowest sand specimens and have taken them at any time," says chemistry professor Caltech Brian Stolz, co-author of a new study published in the magazine. ACS Central Science. "When I saw the results for the first time, my work lay on the floor." In the original edition of Chemrxiv's print server, in mid-October, it contained more than 35,000 views.

The method works best on small molecular models, when the specimens look simple powder, they actually contain about a billion times smaller crystals than dust. Researchers knew about these hidden microcrysts, but did not realize that they could easily open the crystalline molecular structure through MicroED. "People do not think how often microscopes are in powder specimens," says Stolz. "It's like science fiction, and I think it's going to be my life, and these structures can be seen in powders."

There are consequences for chemists who want to detect the structure of small molecules, whose results are determined to be less than about 900 daltons. (A dallon is the mass of the hydrogen atom.) These small compounds include some of the chemicals found in nature, some biological substances such as hormones, and some therapeutic preparations. Potentially add-ons of the MicroED's structured methodology include drug detection, criminal laboratory analysis, medical testing, and more. For example, according to Stolz, the method can be used by athletes to test the most effective productivity, but only the number of chemicals.

"The slowest step in the production of new molecules determines the structure of the product as it promotes organic chemistry by revolution," said Kertic Victor and Elizabeth Atkins, professor of chemistry, Robert Grabbs, and Nobel Prize winner in chemistry in 2005, who did not take part in the study. "The last major breakthrough in defining the structure was by nuclear magnetic resonance spectroscopy, which was introduced by Robert Roberts in Caltex in the late 1960s."

Like other synthetic chemists, Stoltz and its team are trying to figure out how to collect chemicals from the main materials in the laboratory. Their laboratory prioritizes natural small molecules, such as beta-lactam family, which extracts of compounds belonging to penicillins. In order to make these chemicals, they must determine the structure of the molecules in their reactions – to see if intermediate molecules and end products are in the right path.

One of the ways to do this is an X-ray crystallography that contains X-rays that separate the chemical from the atoms. The diffracting X-rays sample shows the 3-D structure of the targeted chemistry. Often this method is used to solve the structure of large molecules, such as complex membrane proteins, but also to small molecules. The problem is that to do this, the chemist needs to build a well-sized three-dimensional particle, which is not always easy. Stolz says: "Once I tried to get the right crystal for one of my models.

Another reliable method is that crystals are not needed, but require a large number of NMR (nuclear magnetic resonance) patterns. NMR also provides indirect structural information.

Previously, trace elements are similar to X-ray crystals, but they use electrons instead of x-rays – are mainly used in crystalline proteins rather than in small molecules. The author of the UCLA's electronic crystal graphics author, author Tamer Honsen, began working on Howard Hughes Medical Institute in Virginia, for the production of proteins for MicroED technology. After moving to UCLA, he began to think about the use of the method in small molecules. With Caltech.

"Tumor has been used with this protein technique and they can only work occasionally using powdered specimens of proteins," says Jose Nelson, Associate Professor of the Department of Chemistry and Biochemistry UCLA (PhD & # 13). "In my opinion, because these crystals did not have to grow, I realized that we could inject this method into a new class of molecules that would have a wider effect on all types. chemistry

The team tested several different properties, never attempted to crystallize and was able to detect their structures thanks to their extensive microcrystals. They managed to obtain designs for Tylenol and Advil drugs, and they were able to identify specific structures from the powder mixture of four chemicals.

The UCLA / Caltech group hopes that this will be a daily routine in chemistry labs.

"Our labs have pupils and post-doctors who make new and unique molecular laws daily," says Stolz. "Now we can quickly determine if they can change their synthetic chemistry."

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