Silver-Based Terpyridine Complexes as Antitumor Agents.

Silver complexes bearing substituted terpyridine or tetra-2-pyridinylpyrazine ligands have been prepared and structurally characterised. The study of the anticancer properties of silver complexes with this type of ligands is scarce, despite the possibilities of combining the properties of the metal and the ability of the ligands for DNA binding. Here, the antiproliferative activity, stability, CT-DNA binding, and mechanism of cell death of these types of derivatives are studied. High cytotoxicity against different tumour cells was observed, and, more important, a great selectivity index has been detected between tumour cells and healthy lymphocytes T for some of these compounds. The CT-DNA interaction study has shown that these derivatives are able to interact with CT-DNA by moderate intercalation. Furthermore, cell death studies indicate that these derivatives promote the apoptosis by a mitochondrial pathway.

Switching On/Off of a Solvent Coordination in a Au(I)-Pb(II) Complex: High Pressure and Temperature as External Stimuli.

The benzonitrile solvate {[{Au(C6F5)2}2{Pb(terpy)}]·NCPh}n (1) (terpy = 2,2':6',2″-terpyridine) displays reversible reorientation and coordination of the benzonitrile molecule to lead upon external stimuli. High-pressure X-ray diffraction studies between 0 and 2.1 GPa reveal a 100% of conversion without loss of symmetry, which is totally reversible upon decompression. By variable-temperature X-ray diffraction studies between 100 and 285 K, a partial coordination is achieved.

Synthesis and Structural Characterization of Phosphanide Gold(III)/Gold(I) Complexes and Their Thallium(III) and Gold(III) Precursors.

In this paper, we describe a series of diphenylphosphane and diphenylphosphanide gold(III) and gold(III)/gold(I) complexes containing 3,5-C6Cl2F3 as aryl ligands at gold that have been synthesized due to the arylating and oxidant properties of the new polymeric thallium(III) complex [TlCl(3,5-C6Cl2F3)2]n (1). Its reaction with [Au(3,5-C6Cl2F3)(tht)] (tht = tetrahydrothiophene) produces the gold(III) complex [Au(3,5-C6Cl2F3)3(tht)] (2), which allows the synthesis of the diphenylohosphane derivative [Au(3,5-C6Cl2F3)3(PPh2H)] (3). Its treatment with acetylacetonate gold(I) derivatives leads to two novel AuIII/AuI phosphanido-bridged complexes, [PPN][Au(3,5-C6Cl2F3)3(µ-PPh2)AuCl] (4) and [PPN][{(3,5-C6Cl2F3)3Au(µ-PPh2)}2Au] (5). All these complexes have been characterized, and the crystal structures of 1, 2, 4 and 5 have been established by single crystal X-ray diffraction methods, showing a novel polymeric arrangement in 1.

Deciphering the Primary Role of Au⋠⋠⋠H-X Hydrogen Bonding in Gold Catalysis.

Au⋅⋅⋅H-X (X=N or C) hydrogen bonding is gaining increasing interest, both in the study of its intrinsic nature and in their operability in different fields. While the role of these interactions has been studied in the stabilization of gold(I) complexes, their role during the minimum free energy reaction pathway of a given catalytic process remains unexplored. We report herein that complex [Au(C≡CPh)(pip)] (pip=piperidine) catalyses the A3 -coupling reaction for the synthesis of propargylamines, thanks to the ability of Au(I) to promote weak hydrogen bonding interactions with the reactants along the free energy profile. Density Functional Theory (DFT) calculations show that these Au⋅⋅⋅H-X interactions play a directing role in the catalysed A3 -coupling. Topological non-covalent interactions (NCI), interaction region indicator (IRI) and quantum theory of atoms in molecules (QTAIM) analysis in real space of the electron density provide a description of these interactions accurately.

Severe bradycardia in a teenager as the initial manifestation for Guillain Barré syndrome: a case report.

BACKGROUND: Guillain-Barré syndrome is the most common cause of flaccid paralysis, with multiple known clinical variants. Autonomic dysfunction, although frequently reported in the clinical course, is often overlooked in the pediatric population and is usually not the initial presenting symptom in this age group CASE PRESENTATION: We present the case of a previously healthy 17-year-old who arrived at the Emergency Department complaining of gastrointestinal symptoms associated with lipothymia. An initial electrocardiogram (ECG) showed sustained sinus bradycardia subsequently associated with arterial hypertension. Structural and inflammatory cardiac pathology were ruled out, as well as auriculoventricular conduction block and posterior reversible encephalopathy syndrome. On the ninth day after initial symptoms, the patient presented sensory and motor nerve disturbances with the cerebrospinal fluid analysis showing a clear albumin-cytologic dissociation, consistent with an atypical presentation of GBS with autonomic dysfunction. Immunoglobulin therapy was administered, developing subsequent aseptic meningitis, that required discontinuation of previous therapy and treatment with plasmapheresis. Clinical improvement was achieved with full motor function recovery. CONCLUSION: This case illustrates a Guillain-Barré syndrome variant in which autonomic dysfunction preceded neurologic deficit, a finding uncommon in children, emphasizing this as an important differential diagnosis for severe bradycardia in pediatric patients.

Time-Dependent Molecular Rearrangement of [Au(N9-adeninate)(PTA)] in Aqueous Solution and Aggregation-Induced Emission in a Hydrogel Matrix.

An in-depth study of the molecular rearrangement of the complex [Au(N9-adeninate)(PTA)] (1), promoted in aqueous solution, is presented. This complex, which has been previously described as forming dimers in its crystalline form, is also demonstrated as being able to assemble into an infinite AuI···AuI chain polymer. The structural motifs are tentatively related to the dramatic modification of the photoemissive properties of 1 in water solution at long times, with the aid of UV-vis and photoluminescence measurements, PGSE-NMR, and theoretical calculations. A subtle equilibrium in favor of aurophilically governed aggregates has been envisaged as the driving force of the molecular rearrangement. Furthermore, 1 has been explored as an additive of the hydrogel of [Au(N9-adeninate)(PMe3)] (2) for a further tuning of its photophysical properties without loss of the gel texture.

Computational prediction of Au(I)-Pb(II) bonding in coordination complexes and study of the factors affecting the formation of Au(I)-E(II) (E = Ge, Sn, Pb) covalent bonds.

We have studied computationally the Au-M (M = Ge, Sn, Pb) bonding trends in a series of model systems [(PH3)3Au-(MCl3)] (M = Ge (4), Sn (5), Pb (6)). For this, we have fully optimized the model systems at the MP2 level of theory, computing the Au-M bonding energy at the equilibrium distances applying the counterpoise (cp) correction to the basis-set superposition error (BSSE) and performing a natural energy decomposition analysis (NEDA). Furthermore, a topological analysis of the electron density using QTAIM, ELF and DORI tools was performed. In order to provide further insights on the possibility of predicting the existence of Au(i)-Pb(ii) donor bonds, Density Functional Theory calculations using the pbe functional and including dispersion corrections (DFT-D3/pbe) were performed on three model systems, [(PR3)3Au-(PbCl3)] (R = CH3 (7), H (8), CF3 (9)). This study also includes the corresponding NEDA calculations and the topological analysis of the electron density, which provides information about the Au-Pb bond, but also about the supporting weak ligand-ligand interactions. Overall, the study provides information about the factors affecting the formation of stabilizing Au(i)-Pb(ii) covalent bonds.

Rational Assembly of Metallophilic Gold(I)-Lead(II) and Gold(I)-Gold(I) Puzzle Pieces.

The assembly of two different building blocks, [{Au(C6 F5 )2 }{PbCl(terpy)}] (terpy=2,2':6':2''-terpyridine) and [{Au(C6 F5 )2 }2 {Pb(terpy)}]n , acting as terminal or central pieces, respectively, gives rise to a decanuclear complex built via metallophilic and π-stacking interactions in which the number of AuI ⋅⋅⋅AuI and AuI ⋅⋅⋅PbII contacts is finely controlled.

Structural and Luminescence Properties of Heteronuclear Gold(I)/Thallium(I) Complexes Featuring Metallophilic Interactions Tuned by Quinoline Pendant Arm Derivatives of Mixed Donor Macrocycles.

Reaction of the heterometallic complex [{Au(C6F5)2}Tl]n with the quinoline pendant arm derivatives L1 and L2 of the mixed donor macrocycles [12]aneNS2O and PhenNS2 affords the new Au(I)/Tl(I) complexes [{Au(C6F5)2}Tl(L1)] (1), [{Au(C6F5)2}Tl(L2)] (2), [{Au(C6F5)2Tl}{Au(C6F5)2Tl(L1)}]2 (3), and [{Au(C6F5)2Tl}{Au(C6F5)2Tl(L2)}]n (4) depending on the reaction molar ratios used. These complexes present different optical properties strictly related to their structural features and to the presence of Au(I)···Tl(I) metallophilic interactions, which are finely tuned by the coordinating quinoline moiety and have been studied experimentally and theoretically via TD-DFT calculations.

Perhalophenyl Three-Coordinate Gold(I) Complexes as TADF Emitters: A Photophysical Study from Experimental and Computational Viewpoints.

We report the synthesis of novel perhalophenyl three-coordinated gold(I) complexes using 1,2-bis(diphenylphosphino)benzene (dppBz) as the chelating ligand and [AuR(tht)] (R = C6F5, C6Cl2F3, C6Cl5) as the perhalophenyl-gold(I) source, leading to [AuR(dppBz)] (R = C6F5 (1), C6Cl2F3 (2), C6Cl5 (3)) complexes. The solid-state structures of compounds 2 and 3 consist of discrete three-coordinated Au(I) complexes, which show a distorted trigonal planar geometry for the gold center with dissimilar Au-P distances. The distorted structural arrangement is closely related to its photophysical properties. The studied complexes display very intense emissions at room temperature (RT) and at 77 K in the solid state. Studies of the emissive properties of the complexes at different temperatures suggest that the emissions are phosphorescent at 77 K and exhibit thermally activated delayed fluorescence (TADF) at RT. First-principle calculations of the photophysical processes yielded rate constants for intersystem crossing and reverse intersystem crossing that are in excellent agreement with experimental data.

Zigzag vs Helicoidal Gold-Silver 1D Chains: Influence of Subtle Interactions in the Spatial Arrangement of Supramolecular Systems.

The reaction of 4'-(2-thienyl)-2,2':6',2,2''-terpyridine (S-terpy) with the heterometallic complexes [Au2Ag2R4(OEt2)2]n (R = C6F5, C6Cl5) leads to the compounds [{Au(C6X5)2}Ag(S-terpy)]n (X = F (1), Cl (2)). The X-ray diffraction analysis of the complexes shows an alternating disposition of the metals -Au-Ag-Au-Ag- in 1D infinite polymeric chains. Despite the fact of having the same metallic sequence, the spatial arrangement observed for both complexes is very different, since for [{Au(C6F5)2}Ag(S-terpy)]n (1) the metals adopt a zigzag disposition, whereas an helicoidal distribution of the interacting metals is observed for the complex [{Au(C6Cl5)2}Ag(S-terpy)]n (2). These different arrangements are related to the perhalophenyl ligands present in the complexes, which appear with different spatial dispositions, being staggered in the case of C6F5 (1) and almost eclipsed in the case of C6Cl5 (2). In order to explain the reasons for these different structural arrangements, we performed a DFT-D3 computational analysis and a subsequent study of the qualitative characterization of the noncovalent interactions (NCIs) in real space.

Stimuli-Responsive Solvatochromic Au(I)-Ag(I) Clusters: Reactivity and Photophysical Properties Induced by the Nature of the Solvent.

Reaction of the heterometallic polymer [Au2Ag2(C6Cl5)4(OEt2)2] n with 4 equiv of pyridazine leads to the new discrete complex [Au2Ag2(C6Cl5)4(µ2-C4H4N2)2(C4H4N2)2] (1). Complex 1 is solvoluminescent, leading to drastic structural changes, depending on the coordination ability of the chosen solvent. Thus, the reaction of complex 1 with acetonitrile leads to a new Au(I)-Ag(I) complex of stoichiometry [Au2Ag2(C6Cl5)4(µ2-C4H4N2)2(NCMe)2] n·2CH3CN(2), while if the reaction is carried out with a noncoordinating solvent such as dichloromethane, complex [Au2Ag2(C6Cl5)4(C4H4N2)2] n·CH2Cl2 (3) is obtained. Furthermore, when complexes 1, 2, and 3 are exposed to tetrahydrofuran, different results are obtained. In the case of complex 1, the metallic core disposition remains and THF is incorporated as a crystallization solvent in [Au2Ag2(C6Cl5)4(µ2-C4H4N2)2(C4H4N2)2]·2THF (1·THF). On the other hand, reaction of complexes 2 or 3 with THF gives rise to a mixture of the corresponding polymeric complex [Au2Ag2(C6Cl5)4(THF)2] n, in which pyridazine ligands are displaced, together with a polymorph of complex 1·THF. All these complexes are luminescent in solid state displaying different emission energies depending on their structural disposition as well as on the presence of the metallophilic interactions. These subtle changes in the cluster structures, only based on the solvent used, lead to spectacular reversible changes in the emissive behavior of the complexes, allowing the tuning of the luminescent emissions in a wide range. DFT and TD-DFT calculations support the experimental photophysical studies.

Dispersive Forces and Dipole Moment Increase as Driving Forces for the Formation of an Unprecedented Metallophilic Heterotrimetallic System.

The crystal structure of the polymeric complex [Au5 Ag2 Tl3 (C6 F5 )10 (L1 )2 ]n (L1 =1-aza-4,10-dithia-7-oxacyclododecane) displays heterotrimetallic Ag⋅⋅⋅Au⋅⋅⋅Tl moieties and is held by unsupported metallophilic interactions. This complex emits at 500 nm in the solid state. Ab initio calculations show that the large thermodynamic stability that helps the formation of this heterotrimetallic system arises from the combination of dispersive forces and a very large dipole moment in the supramolecular arrangement.

Cooperative Au(I)···Au(I) Interactions and Hydrogen Bonding as Origin of a Luminescent Adeninate Hydrogel Formed by Ultrathin Molecular Nanowires.

Two water-soluble [Au(9 N-adeninate)(PR3)] complexes (PR3 = PMe3 (1); PTA (3)) were synthesized by the coordination of the respective cationic [Au(PR3)]+ fragment to the 9 N position of the adeninate anion. Both complexes crystallize as dimers by aurophilic contacts of 3.2081(6) Å in 1 and 3.0942(7) and 3.0969(7) Å in 3, but different packings are observed due to the crystallizing solvent choice and the nature of the ancillary phosphine ligand. At this regard, different supramolecular behavior is observed in water, ranges from the formation of ultrathin nanowires of 5.3 ± 1.9 nm of diameter and up to 1.5 µm in length and leads to a blue-luminescent hydrogel for 1, to the single-crystallization of 3. Parallel computational studies carried out show that aurophilicity and N-H···N or O-H···N hydrogen bonding are comparable in strength, suggesting a competition between all types of weak forces in the final observed macroscopic properties.

Influence of the Number of Metallophilic Interactions and Structures on the Optical Properties of Heterometallic Au/Ag Complexes with Mixed-Donor Macrocyclic Ligands.

The reactivity of the polymeric gold(I)/silver(I) compound [Au2Ag2(C6F5)4(OEt2)2] n toward the 12-membered mixed-donor macrocyclic ligands 1,7-diaza-4,10-dithiacyclododecane (L1), 1-aza-4,7,10-trithiacyclododecane (L2), N-quinolinylmethyl-1-aza-4,7,10-trithiacyclododecane (L3), and N, N'-bis(quinolinylmethyl)-1,7-diaza-4,10-dithiacyclododecane (L4) was studied. The reactions were carried out using different molar ratios depending on the coordination properties of the ligands, which were modified by changing the donor atoms present in the macrocyclic framework (sulfur or nitrogen) or by linking one or two methylquinoline pendant-arms at the secondary nitrogen atom(s). X-ray diffraction analysis of the new complexes obtained show a nuclearity that increases on increasing the number of donor atoms in the ligands. The rich structural diversity observed determines different optical responses when the complexes are irradiated with UV-vis light in the solid state and in THF solution. The study of the optical properties reveals that in complexes for which the luminescence is due to metal-metal interactions, higher emission wavelengths are observed as the number of these metallophilic contacts increases, while the luminescence of ionic complexes has its origin in the macrocyclic ligands. TD-DFT calculations were carried out to verify the origin of these interesting structural-optical property relationships.

Polarized Supramolecular Aggregates Based on Luminescent Perhalogenated Gold Derivatives.

The reaction of [Au(C6F5)(tht)] (tht = tetrahydrothiophene) with 1,3,5-triaza-7-phosphaadamantane (PTA) and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) leads to the formation of [Au(C6F5)(phosph)] (phosph = PTA, 1; phosph = DAPTA, 2). The compounds are slightly soluble in water and aggregate at higher concentrations, giving rise to the formation of needle- and rodlike structures (1) and well-organized spherical aggregates (2). Compounds 1 and 2 were reacted with AgPF6, giving rise to the formation in all cases of luminescent water-soluble 1:1 Au···Ag heterometallic complexes, as evidenced by X-ray crystal structure determination. The use of different silver salts that differ on the counterion induces changes in the resulting luminescence and aggregation morphology.

Tailor-Made Luminescent Polymers through Unusual Metallophilic Interaction Arrays Au···Au···Ag···Ag.

A novel and efficient strategy for the synthesis of luminescent polymers bearing metallophilic interactions with unprecedented charge sequences has been designed. For this end suitable basic gold units such as [AuR2]-, bearing perhalophenyl derivatives, and dinuclear acid silver terpyridine species, [Ag2(terpy)2](CF3SO3)2, have been chosen. Their combination originates the polymeric derivatives [{AuR2}2Ag2(terpy)2]n (R = C6F5, C6Cl2F3) or [{Au(C6Cl5)2}Ag(terpy)]n. The change of the perhalophenyl group in the gold complex modulates the strength in the metallophilic contacts and, consequently, the polymer arrays and luminescent properties. The X-ray diffraction studies of these derivatives revealed that there are polymers with unusual + + - - + + - - charge sequences for the R = C6F5 and C6Cl2F3 species, whereas the more classical + - + - disposition was found for the bulkiest C6Cl5 derivative. Their luminescent properties also vary depending on the formation of these polymer arrays, and time-dependent density functional theory calculations were performed to determine the origin of the luminescence.

Tuning Au(I)···Tl(I) Interactions via Mixed Thia-Aza Macrocyclic Ligands: Effects on the Structural and Luminescence Properties.

Reaction of the heterometallic complexes [{Au(C6X5)2}Tl]n (X = Cl, F) with equimolecular amounts of the N,S-mixed-donor crown ethers [12]aneNS3 or [12]aneN2S2 affords the new Au(I)/Tl(I) derivatives [{Au(C6Cl5)2}{Tl(L)}2][Au(C6Cl5)2] [L = [12]aneNS3 (1), [12]aneN2S2 (2)], [{Au(C6F5)2}Tl([12]aneNS3)]2 (3), or [{Au(C6F5)2}Tl([12]aneN2S2)]n (4). These complexes display the same Au/Tl metal ratio, but different structural arrangements. While the chlorinated derivatives 1 and 2·2THF display an ionic structure, the crystal structure of 3 contains neutral tetranuclear Au2Tl2 units, and complex 4 displays a polymeric nature and is the only one that does not show unsupported Au···Tl interactions. The lack of this interaction is responsible for the absence of luminescence in this last case. The optical properties of 1 and 3 in the solid state have been studied experimentally and theoretically, concluding that their luminescence has its origin in the Au···Tl interactions, and this is also influenced by their number and strength. DFT and TD-DFT theoretical calculations on model systems of complexes 1, 3, and 4 have been carried out in order to confirm the origin of their luminescence or its absence, as well as to justify their emission energies in spite of their different solid state structures.

Tuning the Luminescent Properties of a Ag/Au Tetranuclear Complex Featuring Metallophilic Interactions via Solvent-Dependent Structural Isomerization.

In this paper the reaction products of the basic gold(I) species [Au(C6Cl5)2]- against the acid salt Ag(OClO3) in the presence of the S-donor macrocyclic ligand 1,4,7-trithiacyclononane ([9]aneS3) are studied in different solvents. Two different isomers of stoichiometry [{Au(C6Cl5)2}Ag([9]aneS3)]2 were isolated depending on the solvent used, dichloromethane or tetrahydrofuran, which show different luminescence in the solid state. X-ray diffraction studies of these compounds reveals that both show the same heteropolynuclear Ag···Au···Au···Ag system but with different Au···Au interaction distances and different relative positions of the cationic fragment [Ag([9]aneS3)]+ in the structure with respect the bimetallic Au···Au core. This work includes a study of the optical properties of both isomers, as well as time-dependent density functional theory calculations that were performed to determine the origin of their different luminescence.

New Insights into the Au(I)···Pb(II) Closed-Shell Interaction: Tuning of the Emissive Properties with the Intermetallic Distance.

Reaction of [Au2Ag2R4(Et2O)2] (R = C6Cl2F3- or C6F5-) with [Pb{HB(pz)3}]Cl in a 1:2 molar ratio led to complexes [AuPb{HB(pz)3}R2] (R = C6Cl2F3- (2) or C6F5- (3)) through transmetalation reactions. The crystal structures of these complexes display unsupported Au(I)···Pb(II) interactions of 3.0954(4) (2) and 3.2778(4) (3) Å, together with one (2) or two (3) F···Pb weak contacts. These intermetallic distances are compared to the shortest one found for the previously reported complex [Pb{HB(pz)3}Au(C6Cl5)2] (1) of 3.0494(4) (1) Å, showing a clear dependence with the donating properties of the different aurate units. The complexes are emissive in the solid state due to charge transfer transitions associated with the presence of Au(I)···Pb(II) interactions, in which the intermetallic distance plays a crucial role. Density functional theory and time-dependent density functional theory calculations support the assignment of the luminescent properties of the complexes. Ab initio Hartree-Fock and MP2 calculations on model systems of complexes 2 and 3 show the presence of strong Au(I)···Pb(II) closed-shell interactions of an ionic plus dispersive nature together with weak F···Pb contacts of a dispersive origin in the case of complexes 2 and 3.