Diego Martínez-Otero

We studied the influence of bridging chalcogen atoms (μ-E; E = S, Se) on the structure and reactivity of digallium dihydroxide complexes [{MeLGa(OH)}2(μ-E)] [E = S (4), Se (5); MeL = CH{CMe(NAr)}2–, Ar = 2,4,6-Me3C6H2]. Compounds 4 and 5 were synthesized from MeLGaCl2 and sodium chalcogenide (Na2E) in THF-NH3(l), followed by controlled hydrolysis. For the sulfur system, the intermediates [{MeLGa(Cl)}2(μ-S)] (2) and [{MeLGa(NH2)}2(μ-S)] (3) were isolated and characterized, whereas the corresponding selenium derivatives proved too reactive for isolation. The reactivity of 4 and 5 toward Group 4 metal amides, M(NR2)4 (M = Ti, R = Me; M = Zr, Hf, R = Et), revealed a chalcogen effect, affording both monocyclic and spirocyclic complexes from 4, while 5 selectively yielded spirocyclic complexes. Likewise, the milder amide Me2Si(NMe2)2 reacted exclusively with 5 to produce a siloxide-bridged derivative. Distinct borane-dependent pathways were also observed. Treatment of 4 and 5 with BH3·THF resulted in the Ga–OH protonolysis to form cyclic borates, whereas BH3·SMe2 promoted hydride attack at gallium, yielding gallium hydrides. These results provide an insight into the ambiphilic character of 4 and 5 and establish chalcogen bridging as a strategy for tuning their bonding and reactivity.

In this paper, we explore different strategies that can serve as models for both the design and delivery of candidate antitumoral molecules intended for cancer therapy. For example, a novel platinum-based compound, called 1.Cl, was synthesized, and its interaction with the iron-transport protein transferrin, proposed as a potential targeted drug delivery system, was studied. The synthesis of 1.Cl and its interaction with transferrin were studied using a multimethodological approach based on spectroscopic, thermodynamic, and solid-state methods, including UV–vis absorption and emission spectroscopy, isothermal titration calorimetry, differential scanning calorimetry, and protein crystal X-ray diffraction. The successful synthesis and design of 1.Cl, a compound with structural and chemical properties that may enable antitumoral activity, along with the study of its interaction with a native iron-transport protein, provide a promising foundation for the design of potential cancer drugs. The results indicate that 1.Cl interacts with transferrin effectively in solution, supporting the hypothesis that this protein can be used as a selective delivery system to enhance cytotoxicity in malignant cells while reducing side effects.

1-Phenyl-4-p-tolyl-[1,2,3]triazole was obtained via a CuAAC reaction involving phenyl azide and 1-ethynyl-4-methylbenzene. The NMR spectra of the compound are discussed, and its crystal structure was studied by X-ray analysis. According to the latter analysis and a Hirshfeld surface analysis, the predominant intermolecular C-H⋅⋅⋅N and C-H⋅⋅⋅π interactions in this molecule are responsible for crystal packing.

This work describes synthetic routes to dicationic imidazolium chlorides bearing allylic substituents and the p-xylyl and o-xylyl spacers, and their reactivity studies aimed to synthesize silver(I) N-heterocyclic monocarbene derivatives. The synthesis of the chlorides {pXiAlImo}Cl2 (1), {pXiMeAlImo}Cl2 (2), [oXiAlImo]Cl2 (3) and [oXiMeAlImo]Cl2 (4) was carried out using a two-step methodology, in which the reaction times, solvents, temperature, and base used were evaluated. The synthesized salts 1 to 4 were used to produce NHC-Ag(I) carbenes via the silver oxide route, which allowed the formation of the silver(I) metallic compounds [Ag2Cl2{pXiAlImil}] (1a), [Ag2Cl2{pXiMeAlImil}] (2a) [Ag2Cl2{oXiAlImil}] (3a) and [Ag2Cl2{oXiMeAlImil}] (4a) with moderate yields. Single-crystal X-ray Diffraction analysis confirmed the solid-state structure of salts 1 and 2. NMR, IR, and HR-MS spectra were used to characterize all compounds to verify the proposed structures. The antibacterial activity of the synthesized silver(I) NHC carbenes was evaluated by determining the minimum inhibitory concentration (MIC) and the inhibition halo by the Kirby-Bauer method against two Gram-positive bacteria (B. subtilis and S. aureus), and two Gram-negative bacteria (P. aeruginosa and E. coli).

A collection of 40 derivatives of 1,2-diphenyl-2-[1,2,3]triazol-1-yl-ethanol was obtained through a sequence of reactions, starting with benzoin as the initial raw material and using the CuAAC reaction as the key step in this process. The structure of a pair of these compounds was ultimately corroborated by single-crystal X-ray diffraction studies, which also reveals important O-H···N interactions. The antimicrobial activity of synthesized 1,2,3-triazoles was assessed against strains that include Candida albicans and Staphylococcus aureus. The antiproliferative properties of some of these novel compounds were also tested using a variety of tumor cell lines, including U251 (human glioblastoma), PC-3 (human prostate cancer cell line), K562 (human leukemia), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human breast adenocarcinoma), and SKLU (human lung adenocarcinoma).

Selective neurotransmitter recognition and sensing in aqueous media by artificial receptors is an attractive, but challenging goal in modern supramolecular chemistry. Despite advances in the development of optical receptors for some neurotransmitters, such as dopamine, little effort has been invested in developing receptors for epinephrine, a paramount importance neurotransmitter and a globally used drug for heart attacks. Herein, a new fluorescent molecular receptor based on 1,3-bis-benzimidazole-benzene derivative covalently linked to two phenyl boronic acids, 1 was synthesized, structurally described by single-crystal X-ray diffraction, and studied in-depth as receptor for four catecholamine-based neurotransmitters and several nucleosides, monosaccharides and L-tyrosine in water at physiological pH. Receptor 1 is hydrostable with fluorescence emission at 408 nm, originated by intraligand (IL) [π-π*] transitions as evidenced by TD-DFT calculations. Additions of epinephrine/norepinephrine at the micromolar concentration level to aqueous solution of 1 induce significant fast fluorescence changes, whereas in the presence of dopamine, L-DOPA, adenosine, guanosine, glucose, fructose, galactose, ribose and L-tyr, only modest optical changes are observed. Bis-boronic receptor 1 was found to have a high affinity for epinephrine (K= 1.29x10⁵ M^-1) with good selectivity over other closely neurotransmitters including dopamine and L-DOPA. The affinity of epinephrine for 1 is an order of magnitude greater than that for norepinephrine. Such epinephrine affinity/selectivity for a molecular receptor is still rare. On the basis of spectroscopic tools (fluorescence, ¹¹B NMR, lifetimes), mass spectrometry, X-ray crystal structure of 1, DFT calculations and Atoms in Molecule analysis, receptor is bound to epinephrine in a 1:2 (receptor:analyte) mode through two-point recognition that includes a sp³ boronate–catechol condensation and multiple hydrogen bonds of type OH…N and NH…N between the aliphatic chain of epinephrine and imidazole ring from 1 as well as intermolecular interactions between the two epinephrine molecules in the final supramolecular structure. The efficient fluorescent response of 1 with epinephrine can be utilized in quantitative sensing of this bioanalyte in real pharmaceutical samples. Furthermore, a chromogenic sensing ensemble was prepared using 1 with the commercial dye Alizarin Red S where epinephrine is visually detected by an indicator displacement assay through a color change in micromolar concentration range.