A Semi‐Automated, High‐Throughput Approach for the Synthesis and Identification of Highly Photo‐Cytotoxic Iridium Complexes
Name
Angew Chem Int Ed - 2024 - Kench - A Semi‐Automated High‐Throughput Approach for the Synthesis and Identification of.pdf
Description
Published version
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9.97 MB
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Adobe PDF
Checksum (MD5)
6093f17cb4c849065c1c42ce16337e20
Author(s)
Kench, Timothy
Rahardjo, Arielle
Terrones, Gianmarco G
Bellamkonda, Adinarayana
Maher, Thomas E
Storch, Marko
Kulik, Heather J
Vilar, Ramon
Date Issued
February 26, 2024
Journal
Angewandte Chemie International Edition
Publisher
Wiley
Citation
T. Kench, A. Rahardjo, G. G. Terrones, A. Bellamkonda, T. E. Maher, M. Storch, H. J. Kulik, R. Vilar, Angew. Chem. Int. Ed. 2024, 63, e202401808.
Version
Final published version
Abstract
The discovery of new compounds with pharmacological properties is usually a lengthy, laborious and expensive process. Thus, there is increasing interest in developing workflows that allow for the rapid synthesis and evaluation of libraries of compounds with the aim of identifying leads for further drug development. Herein, we apply combinatorial synthesis to build a library of 90 iridium(III) complexes (81 of which are new) over two synthesise‐and‐test cycles, with the aim of identifying potential agents for photodynamic therapy. We demonstrate the power of this approach by identifying highly active complexes that are well‐tolerated in the dark but display very low nM phototoxicity against cancer cells. To build a detailed structure–activity relationship for this class of compounds we have used density functional theory (DFT) calculations to determine some key electronic parameters and study correlations with the experimental data. Finally, we present an optimised semi‐automated synthesise‐and‐test protocol to obtain multiplex data within 72 hours.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1002/anie.202401808
