GRai Christensen, a 15-year-old 11th grade student, took part in a “citizen science” project to understand how different crystals in mussel shells form. But unlike most school experiments, the samples she and her 1,000 middle school students prepared were blasted by scientists in a particle accelerator using her X-rays, which are 10 billion times brighter than the sun’s. Ta.
“It was kind of eye-opening,” Christensen said of the study, called Project M, which involved students from 110 schools. They prepared various samples of calcium carbonate (the main component of mussel shells), which the scientists tested at the UK’s national laboratory. synchrotron (a type of circular particle accelerator), Oxfordshire Diamond Light Source. The aim was to help scientists better understand how different types of crystal structures can be formed from the same chemical. “After that, I became more interested in chemistry,” says Christensen. He studied agriculture at Glosten Randburgskole in Denmark. “Chemistry really helped me gain insight into the natural world.”
But while such approaches may be new, understanding how crystals form is an old problem with serious implications. Crystal structure not only affects the strength of steel, but it can also affect the therapeutic activity of drugs developed to treat AIDS and Parkinson’s disease.
Calcium carbonate is the main compound in rocks such as chalk, limestone, and marble, which are derived from organic materials such as shells. In addition to causing pesky limescale stains around faucets, it has useful uses on everything from antacid tablets to concrete blocks. “Calcium carbonate is all around us,” says chemist Dr Claire Murray, who led Project M in 2017 with colleagues and fellow chemists from the Institute of Chemistry. diamond light source, Dr. Julia Parker. However, one notable challenge is controlling their crystalline morphology.
A crystal is a solid whose components are arranged in a highly regular repeating pattern, and the shape of this pattern, or crystal structure, determines the material’s properties. A common example of crystal structure effects is carbon. If the atoms are in a sheet of honeycomb lattice of pencil lead (graphite), it’s useful for jotting down notes, but if the atoms are arranged it’s much harder and much more expensive. The cubic crystal lattice that forms diamonds.
For other materials, controlling a material’s possible crystalline structure, or “polymorphism,” has been a matter of life and death. In the early 1980s, life expectancy after an AIDS-related diagnosis was less than 2 years. Patient outcomes began to improve significantly by his mid-1990s, thanks to the development of antiretroviral treatments, including a drug called ritonavir. However, two years after its initial launch in 1996, the drug was withdrawn from the market due to stability issues. Its crystal structure.
Ritonavir capsules were originally formulated as a highly concentrated solution of the active ingredient. Unfortunately, these conditions cause structural changes in the active drug, making it less soluble than the original drug and thus significantly less effective as a drug. Later, the development of further drugs solved the problem.However, the Parkinson’s disease drug rotigotine faced similar problems in 2008 with the appearance of a crystalline structure with poor solubility, prompting a mass recall in Europe, while the drug remained out of stock in the United States until 2012. However, at that time, drug developers Found a reformulation.
“There are many recent examples, but not all are publicly available,” says Dr. Marcus Neumann, CEO and science and technology director of Avantgarde Materials Simulation (AMS), a German company that develops software for predicting crystal structures. say. “Instances that affect drugs that are already on the market will be made public. And fortunately, things like that don’t happen very often.”
For more than 20 years, AMS has developed a computer code that can predict what crystal structure will form for a given compound, helping pharmaceutical companies discover problematic polymorphisms before they bring a drug to market. I’ve been working on development. 2019AMS has shown that its code can predict the appearance of problematic forms of rotigotine. recent updates The algorithm incorporates the effects of temperature and humidity, and is also used by AMS manufacturers such as AstraZeneca, Novartis, AbbVie (which makes reformulated ritonavir), and UCB Pharma (which makes reformulated rotigotine patch). Comparisons with crystal structure data from the pharmaceutical companies we work with are also used. ).
Nevertheless, determining the experimental conditions required to produce a particular crystal remains difficult, as small changes in conditions can generate different structures and transform one structure into another. It Is difficult. You can think of it like a stack of oranges in a box. If you lay out a grid of orange squares and place each orange on the top layer directly above the orange on the bottom, it will balance out nicely for a while. However, with a simple tap, the top orange will fit into the depression between the oranges in the bottom layer, creating a more stable structure.
“Many factors are not 100% understood when it comes to how to achieve a particular crystal structure, so there is still a lot of experimentation needed,” says Merck, head of materials science research and development in Life Sciences. says Dr. Adam Roe. He emphasizes that “a number of factors can come into play” when introducing additives to tune a system toward a specific crystal structure, which is exactly the approach Project M explored. .
Calcium carbonate has three possible crystal structures: aragonite, vaterite, and calcite. Dr Julia Parker says mussels are grown by choosing what they need (for example, durable calcite for their outer shells) and “without harsh chemical conditions”. “It’s just an additive, an organic molecule.” Parker and Murray wondered whether the growth of vaterite and calcite could be controlled by using the right additives at the right concentrations.
With the diamond light source, the duo was able to quickly identify small changes in the crystal structure of hundreds of samples by studying the paths in which X-rays from the synchrotron were scattered from the lattice of each crystal. (A synchrotron accelerates electrons and emits his x-rays as they change direction to move around them.) Until this idea was brought into collaboration with the British, the bottleneck was the additives used All samples were to be prepared to test factors such as , concentration, and mixing time. It can also be used in schools, taking advantage of similarities in laboratory and environmental conditions.
Christensen and fellow students from Didcot School for Girls, based near Diamond, were the first to try out the sample preparation kits and helped guide Parker and Murray to the equipment and instructions needed for each kit. The data needed to characterize each sample was collected in just one day on a synchrotron.
resultThe paper, published in January this year, helps elucidate the conditions that significantly promote or prevent vaterite formation and provides insight into how these crystals form. “I think we’ve made progress in showing which factors are most likely responsible for biocalcification.” [living creatures making minerals] The formation of these calcium carbonate crystals in biological applications is also possible,” says Raw. “But, of course, there is still a lot of work to do.” But the results of this project were not only scientific. A school participant who was passionate about chemistry then came to Diamond for an internship interview.
“With this project, it felt like we were doing something for the real world, rather than just an experiment in school,” says Christensen.
