Experimental and Theoretical Studies for Site-Selective Fluorination of Complex Molecules

• Grant number: 24/04937-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Rodrigo Antonio Cormanich
• Grantee: Guilherme Cariello Silva
• Supervisor: Thomas Lectka
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Johns Hopkins University (JHU), United States
• Associated to the scholarship: 22/16188-8 - Computational and experimental studies of hydrogen bonding involving organic F atoms as acceptors, BP.DR

Abstract

Organofluorine compounds represent, approximately, 30% of pharmaceutical and agrochemical compounds in the market nowadays. C-F bonds are classic bioisosteres of the C-H and the C-O bonds. However, the fluorinated analogs may exhibit altered reactivity and stability, including their geometry and conformation. This difference is mainly due to two chemical factors: the electronegative of the fluorine atom and the character of the C-F bond. Because of the significant contrast in electronegativity of the F atom when compared to the H and the C atom (3.98, 2.20, and 2.55 respectively based on the Pauling Scale) and a similar size, different physical-chemistry properties may be observed in organofluorine compounds. Also, the elevated electrostatic character of C-F bonds increases their thermodynamic stability, causing the molecules to be unreactive toward metabolic and chemical transformations. Commonly, the extremes of fluorination methods have an accentuated or diminish reactivity and do not comprise the rise in molecular complexity. In this fashion way, new methodologies have been developed for fluorination methods in a most suitable condition. The ionophore Monensin A and derivatives are prominent anticancer drugs and Lectka and co-workers demonstrated that its fluorination extended the half-life in rat liver microsomes. The site-selective fluorination method utilized by the group opens a new research area of organofluorine compounds, especially, the synthetic methods to derivatize ionophores and new synthetic uses of its characteristics. In this context, this project aims to expand the ionophore principle to natural products and other molecules to obtain new fluorinated compounds by the site-selective method utilized in Monensin A.