IUCr bursary case studies

In 2016 alone, the IUCr sponsored 40 international meetings and schools. Three recent recipients of IUCr Young Scientist Awards reveal below the importance of these travel grants to their research and experience.

Lanthanoid metal-organic frameworks

Metal-organic frameworks (MOFs) have been extensively studied with small organic molecules and transition metals, and in the past years more and more interest in developing MOFs with lanthanoids has emerged. Lanthanoids are a group of f-block metals with similar chemical behavior, and they tend to have larger coordination numbers and less strict bond directionality compared with d-block transition metals. As hard bases, lanthanoids tend to form coordination compounds with hard acids, and carboxylic acid derivatives are by far the most studied group of ligands. Practical applications for lanthanoid-MOFs (Ln-MOFs) have been studied, and these include, for example, small-molecule capture and storage, gas adsorption, catalysis and metal extraction.

In my PhD studies I have been concentrating on multipodal zwitterionic ligands, which possess carboxylate functionality and thus can be used in Ln-MOFs as organic linkers. The backbone of these linkers is an aromatic center joined by two or more methylene bridges to pyridinecarboxylic acids, which in turn have several substituent configurations available, leading to various isomers. Pyridinecarboxylic acid groups can have several different spatial orientations with respect to the aromatic center because of the freely rotating methylene bridges, and if the ligand has been synthesized from, say, nicotinic acid (3-pyridinecarboxylic acid), there are even more directions for the carboxylic acid to coordinate to, than in the case of isonicotinic acid (4-pyridinecarboxylic acid). One problem associated with high degrees of freedom in these Ln-MOF systems is that they tend to crystallize in several different crystal systems and have different types of disorder within the structure.

The bursary towards attending the 16th BCA/CCG Intensive Teaching School in X-ray Structure Analysis (Durham, UK; 25 March-2 April 2017; http://community.dur.ac.uk/durham.x-ray-school/index.html) was crucial for me to gain new insights in the fundamentals of X-ray crystallography. As my materials in question are intrinsically crystalline, X-ray crystallography is the most powerful way to gain information from MOFs. The contents of the course helped me to critically assess my own work up to this point in a new way, and I gained many new pieces of information to aid my further studies.

Structural and biological study of tin-based complexes against enzymes that propagate cancer

Cisplatin and its subsequent clinical success generated interest in researchers with regard to the use of metal complexes as anticancer drugs. Cisplatin still plays a major role in treating over 90% of testicular cancer cases and is now one of the most successful anticancer drugs available on the market. Cisplatin generally interacts with DNA by inducing programmed cell death (apoptosis). Although cisplatin is used in cancer treatment there are side effects such as anemia, diarrhea, alopecia, petechia, fatigue, nephrotoxicity, emetogenesis, ototoxicity and neurotoxicity. This then opened up research areas in synthesizing metal-based drugs, including developing tin-based anticancer drugs derived from dithiocarbazate Schiff bases.

I have embarked on the structural and biological study of tin-based complexes against four enzymes that propagate cancer: ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II. Sponsorship from the IUCr allowed me to attend the 16th BCA/CCG Intensive Teaching School in X-ray Structure Analysis at Durham U., UK. There, with help from tutors and lecturers, I learned much about the theory behind X-ray crystallography, which enabled me to solve single-crystal X-ray diffraction data while understanding the processes involved. Single-crystal X-ray diffraction analysis allows me to determine the real mode of coordination for docking analysis functions. In addition, I had the opportunity to meet and collaborate with front-line researchers in the field of crystallography from different universities. These connections have helped me to view my project from different perspectives and to gain more understanding on how to better apply single-crystal X-ray data to my own work.

Structure determination of the Schistosoma mansoni enzyme fumarate hydratase, a potential macromolecular target for new antiparasitic drug design

Schistosomiasis is a neglected tropical disease, caused by the parasite Schistosoma, which affects 230 million people worldwide, and is responsible for thousands of deaths every year. In the search for new targets against schistosomiasis, an important strategy involves the identification and characterization of essential enzymes from Schistosoma. The S. mansoni enzyme fumarate hydratase (SmFH) catalyzes the reversible hydration of fumarate to malate and is involved in aerobic processes to obtain energy in the parasite. Thus, an understanding of how the enzyme works allows its evaluation as a potential macromolecular target for new antiparasitic drug design.

I have been studying SmFH and, for a better understanding of the enzyme, have been trying a careful structural analysis. Several crystallization experiments were performed, and an X-ray diffraction data set was collected at Synchrotron SOLEIL, France. However, some difficulties were found in the structure solution. RapiData 2017 (Stanford, CA, USA; April 16-22, 2017; http://smb.slac.stanford.edu/news/rapidata/rapidata-2017/) appeared as a great opportunity to improve my knowledge of data collection and processing. All the tutorials offered by the course made possible a better understanding of crystallization and X-ray data processing, and allowed contact with great researchers in the area. As Brazil is experiencing a major crisis, investment in research is very scarce, which makes it difficult for students to attend courses abroad. Thus, the award granted by the IUCr allowed me to have this experience, which will add so much knowledge in my research area.