Welcome to the Lectka Group Website
Fluorine
Research in the Lectka Lab centers around the element fluorine and its' unique and interesting properties when deployed in organic molecules. Fluorine’s uniqueness comes from its’ incredibly strong electronegativity combined with its’ incredibly small size; it is the most electronegative element on the periodic table while also being roughly the same size as a hydrogen atom. This enables it to easily fit in various places on a molecule while also contributing a strong electronic effect due to its’ localized abundance of electron density. Fluorine is a particularly interesting element in modern medicinal chemistry. Many modern drugs work by binding with an enzyme in the binding pocket, thus inhibiting the enzyme from preforming its' desired function. One could imagine that if there were a ‘positive’ charge somewhere on the enzyme that having a ‘negative’ (fluorine) on the drug molecule aligned with it would increase the affinity between the drug and the enzyme, increasing the potency of the drug. Our lab aims to establish new ways to selectively add fluorines onto small molecules. Additionally, our lab aims to improve the understanding of fluorine’s capabilities. This work is done through our physical organic faction in the lab, where we aim to create unique molecules designed to showcase the capabilities of fluorine that were previously unknown.
Methodology
Today methodology in the Lectka Lab centers on expanding the breadth and capabilities of a mechanism first reported in “Carbonyl-Directed Aliphatic Fluorination: A Special Type of Hydrogen Atom Transfer Beats Out Norrish II” (J. Am. Chem. Soc. 2020). In that publication ketones and enones are used to direct fluorination intramolecularly through a photo-initiated pathway involving Selectfluor and Benzil. Currently we are striving to expand this idea to various other functional groups that possess the requisite Lewis basicity. The future applicability of this chemistry is in the field of medicinal chemistry. As previously stated, fluorine is a highly useful element in the functionality of drug molecules so adding new pathways to selectively insert fluorine onto various areas in a compound opens up more options for creating new and useful pharmaceuticals.
Physical Organic
In our lab we aim to establish a better understanding of the full capabilities of fluorine in organic molecules. This is accomplished by creating new and interesting molecules that functionalize fluorine in ways that were previously unknown or thought to be impossible. For example “Structural proof of a [C–F–C]+ fluoronium cation” (Nat. Comm. 2021) demonstrates, for the first time, that creating a fluoronium ion within an organic molecule is actually possible. This work is done through meticulous planning as well as rigorous organic synthesis. Further studies aim to focus on the donating and stabilization capabilities of fluorine and this work is designed to broaden the scope of understanding about fluorine.
