Theranostics Through the Synergistic Cooperation of Heterometallic Complexes

Heterometallic drugs are emerging as a great alternative to conventional metallodrugs. Careful selection of different metallic fragments makes possible to enhance not only the therapeutic potential by a synergistic effect, but also to incorpore key features like traceability. Drugs that integrate traceability and therapy in one system are known as theranostic agents. In cancer research, theranostic agents are becoming increasingly important. They deliver crucial information regarding their biological interplay that can ultimately be used for optimization. The well-established therapeutic potential of PtII-, RuII- and AuI-based drugs combined with the outstanding optical properties of d6 transition metal complexes grant the delivery of traceable metallodrugs. These species can be easily fine-tuned through modification of their respective ligands to provide a new generation of drugs

Gold catalyzed multicomponent reactions beyond A3 coupling

The preparation of complex architectures has inspired the search for new methods and new processes in organic synthesis. Multicomponent reactions have become an interesting approach to achieve such molecular diversity and complexity. This review intends to illustrate important gold-catalyzed examples for the past ten years leading to interesting skeletons involved in biologically active compounds

Cytotoxic gold(I) complexes with amidophosphine ligands containing thiophene moieties

A new phosphine ligand bearing a thiophene moiety, C 4 H 3 SNHCOCH 2 CH 2 PPh 2 (L), has been prepared by reaction of the aminophosphine Ph 2 PCH 2 CH 2 NH 2 with thiophenecarbonylchloride in the presence of triethylamine. The coordination behavior towards gold(I), gold(III) and silver(I) species has been studied and several metal compounds of different stoichiometry have been achieved, such as [AuL 2 ]OTf, [AuXL] (X = Cl, C 6 F 5 ), [Au(C 6 F 5 ) 3 L], [AgL 2 ]OTf or [Ag(OTf)L]. Additionally, the reactivity of the chloride gold(I) species with biologically relevant thiolates was explored, thus obtaining the neutral thiolate compounds [AuL(SR)] (SR = 2-thiocitosine, 2-thiolpyridine, 2-thiouracil, 2-thionicotinic acid, 2, 3, 4, 6-tetra-6-acetyl-1-thiol-ß-D-glucopyranosato or thiopurine). The antitumor activity of the compounds was measured by the MTT method in several cancer cells and the complexes exhibit excellent cytotoxic activity

Efficient Gold(I) Acyclic Diaminocarbenes for the Synthesis of Propargylamines and Indolizines

Mononuclear gold(I) acyclic diaminocarbenes (ADCs) were prepared by the reaction of 1, 2-cyclohexanediamine with the corresponding isocyanide complexes [AuCl(CNR)] (R = Cy, tBu). The three-component coupling of aldehydes, amines, and alkynes was investigated by using these gold(I) ADC complexes. The new gold(I) metal complexes are highly efficient catalysts for the synthesis of propargylamines and indolizines in the absence of solvent and in mild conditions. This method affords the corresponding final products with excellent yields in short reaction times. Additionally, chiral gold(I) complexes with ADCs have been prepared and tried in the enantioselective synthesis of propargylamines

Luminescent Re(I)/Au(I) Species As Selective Anticancer Agents for HeLa Cells

A series of neutral and cationic heterotrimetallic complexes of the type fac-[Re(CO)3(bipy(CC)2-(AuL)2)X]n, where bipy(CC)2 is 4, 4'-alkynyl-2, 2'-bipyridine; L is either triphenylphosphine (PPh3), [1, 3-bis(2, 6-diisopropylphenyl)-imidazol-2-ylidene] (IPr), or tert-butyl isocyanide (CNtBu); and X is a chloride (n = 0) or acetonitrile (n = 1), were synthesized and characterized together with their Re(I) precursors, i.e., fac-[Re(CO)3(bipy(CC)2)X]n. X-ray diffraction of complexes 1, 3, and 6 corroborated the expected octahedral and linear distribution of the ligands along the Re(I) and Au(I) centers, respectively. Luminescent studies showed that all the complexes displayed a broad emission band centered between 565 and 680 nm, corresponding to a 3MLCT from the Re(I) to the diimine derivative. The presence of the gold fragment coordinated to the diimine ligand shifted in all cases the emission maxima toward higher energies. Such an emission difference could be potentially used for assessing the precise moment of interaction of the probe with the biological target if the gold fragment is implicated. Antiproliferative studies in cancer cells, A549 (lung cancer) and HeLa (cervix cancer), showed a generalized selectivity toward HeLa cells for those heterotrimetallic species incubated at longer times (72 vs 24 h). ICP-MS spectrometry revealed the greater cell internalization of cationic vs neutral species. Preliminary fluorescence microscopy experiments showed a different behavior of the complexes in HeLa and A549 cell lines. Whereas the complexes in A549 were randomly distributed in the outside of the cell, those incubated with HeLa cells were located close to the cellular membrane, suggesting some type of interaction, and possibly explaining their cellular selectivity when it comes to the antiproliferative activity displayed in the different cell lines

Estudio de la densidad mineral ósea mediante osteosonografía en niños y adolescentes sanos: valores de normalidad

Osteoporosis is a frequent health problem in adults. Optimization of bone mass acquisition during childhood and adolescence may play a major role in the prevention of this disease. Osteosonography is a recent technique for measuring bone mineralization without exposing the patient to radiation. OBJECTIVES: To measure bone mineral density using osteosonography in healthy Spanish Caucasian children and adolescents in order to determine normal values. METHODS: We performed a cross sectional study of 829 healthy child and adolescent volunteers (360 girls and 469 boys) randomly selected from the urban area of Pamplona in Navarre (Spain). Ages ranged from 6 to 18 years. ADBM Sonic 1200 ultrasound densitometer from IGEA was used. Daily calcium dietary intake and amount of physical activity were recorded. RESULTS: Cross sectional standards for Ad-SOS are presented. Ad-SOS did not significantly change between the ages of 6 and 9 years in girls or until the age of 10 years in boys. From the ages of 10 to 14 years, Ad-SOS values were higher in girls than in boys. After the age of 14 years, no significant differences were found. No correlation was found between calcium dietary intake, amount of physical exercise or bone mineralization values. CONCLUSIONS: Measurement of Ad-SOS by osteosonography is an easy, fast and inexpensive method for measuring bone mineral density in children and adolescents without exposing them to radiation. It can be used in the pediatric population to detect early alterations in bone mineralization

Gold Thione Complexes

The reaction of the ligand Et4todit (4,5,6,7-Tetrathiocino-[1,2-b:3,4-b']-diimidazolyl-1,3,8,10-tetraethyl-2,9-dithione) with gold complexes leads to the dinuclear gold(I) complexes [{Au(C6F5)}2(Et4todit)] and [Au(Et4todit)]2(OTf)2, which do not contain any gold-gold interactions, or to the gold(III) derivative [{Au(C6F5)3}2(Et4todit)]. The cristal structures have been established by X-ray diffraction studies and show that the gold centers coordinate to the sulfur atoms of the imidazoline-2-thione groups

Gold(I) complexes bearing alkylated 1, 3, 5-triaza-7-phosphaadamantane ligands as thermoresponsive anticancer agents in human colon cells

Overheating can affect solubility or lipophilicity, among other properties, of some an-ticancer drugs. These temperature-dependent changes can improve efficiency and selectivity of the drugs, since they may affect their bioavailability, diffusion through cell membrane or activity. One recent approach to create thermosensitive molecules is the incorporation of fluorine atoms in the chemical structure, since fluor can tune some chemical properties such as binding affinity. Herein we report the anticancer effect of gold derivatives with phosphanes derived from 1, 3, 5-triaza-7-phosphaadamantane (PTA) with long hydrocarbon chains and the homologous fluorinated chains. Besides, we analysed the influence of temperature in the cytotoxic effect. The studied gold(I) complexes with phosphanes derived from PTA showed antiproliferative effect on human colon carcinoma cells (Caco-2/TC7 cell line), probably by inhibiting cellular TrxR causing a dysfunction in the intracellular redox state. In addition, the cell cycle was altered by the activation of p53, and the complexes produce apoptosis through mitochondrial depolarization and the consequent activation of caspase-3. Furthermore, the results suggest that this cytotoxic effect is enhanced by hyperthermia and the presence of polyfluorinated chains. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Temperature-assisted formation of reversible metallophilic Au-Ag interaction arrays

A temperature-controlled self-assembly process in a solution of [Ag(terpy)] n n+ and [Au(C 6 F 5 ) 2 ] - units has been performed. For this, the crystallisation of the complex [{Au(C 6 F 5 ) 2 }Ag(terpy)] n under the same experimental conditions, changing only the temperature, allows the synthesis of polymorphs [{Au(C 6 F 5 ) 2 } 2 Ag 2 (terpy) 2 ] n (2a) at 298 K and [{Au(C 6 F 5 ) 2 }Ag(terpy)] n (2b) at 280 K. The X-ray diffraction studies previously reported for 2a revealed a polymeric structure with an unusual + + - - + + - - charge sequence, whereas for polymorph 2b, a more classical + - + - disposition has been obtained. The conversion of one polymorph into the other can be achieved by simple dissolution of one of them and by recrystallisation at the corresponding temperature. The mechanism of the formation of each polymorph is proposed in view of their 1 H NMR, 1 H-PGSE NMR and molar conductivity measurements

Luminescent gold-thallium derivatives with a pyridine-containing 12-membered aza-thioether macrocycle

The coordination modes of the ligand 2, 5, 8-trithia[9](2, 6)pyridinophane (L) to thallium(i), gold(iii) and gold(i) have been studied. Thallium(i) is coordinated by the macrocyclic ligand in [Tl(L)](PF6) (1) through all the sulfur and nitrogen atoms, in a distorted square-pyramidal geometry with the thallium(i) ion in the apical position and with the presence of an inert lone pair. Gold(iii) is bonded by the ligand only through the nitrogen of the pyridine group in [AuCl3(L)] (2), whereas two AuI-C6F5fragments coordinate the sulfur atoms next to the pyridine moiety of the ligand in [{Au(C6F5)}2(µ-L)] (3), which form a linear polymer through intermolecular aurophilic contacts. The heterometallic TlI/AuIcomplex {[Au(C6F5)2Tl]2(L)}n(4) features a polymeric structural nature with a metallic pseudo-rhombic Au2Tl2core, which repeats itself forming a zig-zag polymer. In each Au2Tl2unit only one thallium atom is bonded by the NS3donor set of the macrocyclic ligand and also forms two unsupported Au-Tl bonds with two [Au(C6F5)2]-units in an overall pseudo-octahedral geometry. The other thallium atom similarly bridges the same [Au(C6F5)2]-units and links a neighbouring Au2Tl2moiety, thus exhibiting a distorted trigonal planar geometry being bonded only to three gold atoms with unsupported Au-Tl interactions. This complex displays an interesting thermochromic behaviour showing emissions mainly resulting from MM'CT transitions at room temperature. At 77 K a dual emission appears, probably arising from the two different thallium environments. DFT calculations have been carried out in the attempt to investigate the origin of the emissions of complex4. © The Royal Society of Chemistry 2021