Structure Determination of Metal Complex/Biomolecule Adducts Using MicroED, an Electron Diffraction Technique

• Grant number: 25/18033-0
• Support Opportunities: Scholarships abroad - Research
• Start date: January 18, 2026
• End date: January 17, 2027
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: João Honorato de Araujo Neto
• Grantee: João Honorato de Araujo Neto
• Host Investigator: Mauro Gemmi
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: IIT Center For Materials Interfaces, Italy

Abstract

Transition metal complexes, particularly ruthenium-based compounds, are promising metallodrugs with distinctive bioactivities compared to platinum derivatives. Their interactions with biomolecules such as DNA, proteins, and enzymes highlight the need for precise tool structural characterization and determination of this interaction modes. Yet, addressing these questions remains challenging, as conventional X-ray crystallography often demands large, well-ordered crystals and, even when successful, frequently yields data of limited resolution, restricting the accurate elucidation of dynamic features essential to understanding metallodrug behavior in the presence of these macromolecules. Microcrystal Electron Diffraction (MicroED) overcomes these challenges, enabling high-resolution structural determination from nanosized crystals while capturing electrostatic details inaccessible to conventional methods. When combined with complementary solution studies (NMR, MS, UV-Vis, EPR), MicroED provides an unprecedented multidimensional view of metallodrug speciation, reactivity, and biomolecular recognition. In this project, we will exploit MicroED to resolve ruthenium-quinolone and ruthenium-naphthoquinone complexes, their speciation products, and adducts with biologically relevant molecules. By directly visualizing drug-biomolecule interactions, we aim to uncover the structural basis of their pharmacological activity. Establishing these methodologies in Brazil, in collaboration with leading groups in electron crystallography, represents a unique opportunity to bridge structural insights with drug development and accelerate the discovery of next generation metallodrugs. (AU)