Dr. David Lozano initially trained in synthetic organic chemistry at the Universitat de Barcelona (Prof. Camps) and CiQUS Universidade de Santiago de Compostela (Prof. Peña), shifted focus to apply his synthetic training to the construction of supramolecular architectures after completion of his PhD. In 2017, he joined the group of Dr. Agustí Lledó at iQCC Universitat de Girona as a postdoctoral research associate to explore the host-guest properties of self-folding cavitands for enzyme mimicry. In 2018, Dr. Lozano moved to the University of Southampton to work in the group of Prof Steve Goldup where he developed novel synthetic methodologies for the synthesis of mechanically chiral interlocked molecules. In 2022, he has joined the group of Prof. Sander Wezenberg at the University of Leiden to employ synthetic molecular machinery, such as stimuli-responsive artificial anion binding and transport systems, to influence biological processes associated with transmembrane transport.
RESEARCH INTERESTS
Supramolecular Chemistry, Organic Chemistry, Transport Mechanisms
Structure-Reactivity Studies of 2-Sulfonylpyrimidines Allow Selective Protein Arylation Maëva M. Pichon, Dawid Drelinkiewicz, David Lozano, Ruxandra Moraru, Laura J. Hayward, et al. Bioconjugate Chemistry, 2023 Protein arylation has attracted much attention for developing new classes of bioconjugates with improved properties. Here, we have evaluated 2-sulfonylpyrimidines as covalent warheads for the mild, chemoselective, and metal free cysteine S-arylation. 2-Sulfonylpyrimidines react rapidly with cysteine, resulting in stable S-heteroarylated adducts at neutral pH. Fine tuning the heterocyclic core and exocyclic leaving group allowed predictable SNAr reactivity in vitro, covering >9 orders of magnitude. Finally, we achieved fast chemo- and regiospecific arylation of a mutant p53 protein and confirmed arylation sites by protein X-ray crystallography. Hence, we report the first example of a protein site specifically S-arylated with iodo-aromatic motifs. Overall, this study provides the most comprehensive structure–reactivity relationship to date on heteroaryl sulfones and highlights 2-sulfonylpyrimidine as a synthetically tractable and protein compatible covalent motif for targeting reactive cysteines, expanding the arsenal of tunable warheads for modern covalent ligand discovery.
A flexible self-folding receptor for coronene David Lozano, Rubén Álvarez-Yebra, Ricard López-Coll, Agustí Lledó Chemical Science, 2019 A hydrogen-bond stabilized cavitand receptor for coronene that has an unprecedented conformational flexibility and adapts to the guest's shape.
Generation and Reactions of an Octacyclic Hindered Pyramidalized Alkene Pelayo Camps, David Lozano, Carla Barbaraci, Merce Font-Bardia, F. Javier Luque, et al. Journal of Organic Chemistry, 2018 Octacyclo[10.6.1.01,10.03,7.04,9.08,19.011,16.013,17]nonadeca-5,8,14-triene (27), a hindered pyramidalized alkene, has been generated from a diiodide precursor. Contrary to the usual behavior of known pyramidalized alkenes, no Diels-Alder adducts were obtained from the present alkene when it was generated by different standard procedures in the presence of different dienes. However, products derived from the reduction, t-BuLi addition, condensation with the solvent, or dimerization were isolated from these reactions, depending on the conditions used to generate it. No [2 + 2] cross product among this pyramidalized alkene and tricyclo[3.3.1.03,7]non-3(7)-ene was formed when a mixture of the corresponding precursor diiodides was reacted with sodium amalgam. The analysis of selected geometrical and orbital parameters determined from quantum mechanical calculations indicates that the degree of pyramidalization of this alkene and its higher steric hindrance compared with other polycyclic pyramidalized alkenes may explain its peculiar reactivity.
Straightforward Synthesis of a Vicinal Double-Bridgehead Iodo Trimethylsilyl Octacycle: Unprecedented Lack of Reactivity of the Silyl Group in the Presence of Fluoride Anions Pelayo Camps, David Lozano, Enrique Guitián, Diego Peña, Dolores Pérez, et al. European Journal of Organic Chemistry, 2017 A convenient synthesis of an octacyclic compound containing an iodo and a trimethylsilyl group in vicinal double-bridgehead positions, as a possible precursor of a pyramidalized alkene, is described. The key step of the synthesis consists of a double nucleophilic substitution of two neopentyl-type iodides by cyclopentadienide anions followed by two intramolecular Diels–Alder cycloadditions. All attempts to generate the expected pyramidalized alkene from the above precursor on reaction with different sources of fluoride failed. This octacyclic compound, which contains two disubstituted C=C bonds, underwent a chemo- and stereoselective Pd0-catalyzed co-cyclotrimerization with dimethyl acetylenedicarboxylate to give a nonacyclic cyclohexadiene derivative that can be aromatized upon reaction with CsF or transformed into a related fluoride upon reaction with AgF.
