TECHNOLOGIES DRUGDISCOVERY TODAY The use of Resonant X-ray Emission Spectroscopy (RXES) for the electronic analysis of metal complexes and their interactions with biomolecules Jacinto Sa ´ 1,2, * , Joanna Czapla-Masztafiak 3,4 , Ewelina Lipiec 3 , Yves Kayser 4 , Wojciech Kwiatek 3 , Bayden Wood 5 , Glen B. Deacon 6 , Gilles Berger 7 , Franc ¸ois Dufrasne 7 , Daniel L.A. Fernandes 1 , Jakub Szlachetko 4,8, * 1 Department of Chemistry, A ˚ ngstro ¨m Laboratory, Uppsala University, Sweden 2 Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland 3 Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow, Poland 4 Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland 5 Centre for Biospectroscopy, School of Chemistry, Monash University, 3800 Victoria, Australia 6 School of Chemistry, Faculty of Science, Monash University, 3800 Victoria, Australia 7 Laboratoire de Chimie Pharmaceutique Organique, Campus Plaine CP205/5, Universite ´ Libre de Bruxelles, Bd du Triomphe, B1050 Brussels, Belgium 8 Institute of Physics, Jan Kochanowski University in Kielce, 25-406 Kielce, Poland This review presents a new application of Resonant X-ray Emission Spectroscopy (RXES) to study the mechanism of action of metal containing anticancer derivatives and in particular platinum in situ and in vivo. The technique is an example of a photon-in photon-out X-ray spectroscopic approach, which enables chemical speciation of drugs to be determined and therefore to derive action mechanisms, and to determine drug binding rates under physiological conditions and ther- apeutic concentrations. This is made feasible due to the atomic specificity and high penetration depth of RXES. The review presents examples of the three main types of information that can be obtained by RXES and establishes an experimental protocol to perfect the measurements within cells. Section editor: Francois M.U. Dufrasne – Universite ´ Libre de Bruxelles, Brussels, Belgium. Introduction Historically chemotherapy with anticancer Pt-drugs began with the FDA approval of cisplatin in 1978, followed by the worldwide marketing of two new compounds: carboplatin and oxaliplatin. Consequently, platinum(II) anticancer drugs are among the most widely used chemotherapeutic agents in general oncology and these three platinum complexes re- main the only metallodrugs in world-wide uses to date in the Drug Discovery Today: Technologies Vol. 16, No. null 2015 Editors-in-Chief Kelvin Lam – Simplex Pharma Advisors, Inc., Boston, MA, USA Henk Timmerman – Vrije Universiteit, The Netherlands Technologies to develop new metal medicines *Corresponding authors: : J. Sa ´(jacinto.sa@kemi.uu.se), J. Szlachetko (jakub.szlachetko@psi.ch) 1740-6749/$ ß 2015 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ddtec.2015.07.001 1