Search Results (43)

Transmetalation, the exchange of metal ions between coordination complexes and biomolecules, has emerged as a powerful design lever in cancer metallopharmacology. Using thiosemicarbazones (TSCs) as a unifying case study, we show how redox-inert carrier states such as zinc(II) or gallium(III) can convert in situ into redox-active copper(II) or iron(III/II) complexes within acidic, metal-rich lysosomes. This conditional activation localizes reactive oxygen species (ROS) generation and iron deprivation to tumor cells. We critically compare redox-active and redox-inert states, delineating how steric and electronic tuning, backbone rigidity, and sulfur-to-selenium substitution govern exchange hierarchies and kinetics. We further map downstream consequences for metal trafficking, lysosomal membrane permeabilization, apoptosis, and ferroptosis. Beyond TSCs, iron(III)-targeted transmetalation from titanium(IV)-chelator “chemical transferrin mimetics” illustrates a generalizable Trojan horse paradigm. We conclude with translational lessons, including mitigation of hemoprotein oxidation via steric shielding, stealth zinc(II) prodrugs, and dual-chelator architectures and outline biomarker, formulation, and imaging strategies that de-risk clinical development. Collectively, these insights establish transmetalation as a central therapeutic principle. We also highlight open challenges such as quantifying in-cell exchange kinetics, predicting speciation under non-equilibrium conditions, and rationally combining these agents with existing therapies. Full article

Density functional theory calculations were performed to elucidate the mechanistic details and origins of the selectivity of the nickel-catalyzed hydroboration of vinylarenes using B₂pin₂/MeOH. The catalytic cycles involved four sequential elementary steps: hydronickelation, anion exchange, transmetalation, and reductive elimination. Kinetic analyses identified hydronickelation as the rate-determining step with an activation barrier of 19.8 kcal/mol, while transmetalation proceeded through a stepwise mechanism characterized by two distinct transition states. Comprehensive analyses of the relevant transition structures and energetics demonstrated that the observed R-enantioselectivity (94% ee) originated from favorable nonbonding interactions. Lastly, our calculations suggested that the Markovnikov regioselectivity was predominantly governed by steric factors rather than electronic effects. Full article

Synthesis of organometallic compounds has had an enormous impact on medicine. In this context, gold complexes are gaining much interest since the discovery of the cytotoxic effect of cisplatin. On the other hand, in the last two decades, the mechanochemical synthetic approaches have been developed considerably demonstrating that they could also be a powerful tool enabling environmentally benign and sustainable synthesis of metal complexes. The present work focuses on mechanochemical synthesis of precursors and gold–NHC complexes of type NHCAuCl and [AubisNHC]⁺. The mechanochemical approach has been studied to afford four substituted imidazoles, eight imidazolium salts and six NHCAuCl and one [AubisNHC]⁺. Substituted imidazoles were obtained with yields varying between 29–99%. Five imidazolium salts bearing aliphatic carbon atoms were obtained, with yields from 46–81%. It is important to notice that the reaction can follow the aging process giving rise to imidazolium salts in very good yields. Concerning the gold(I) complexes, for the first time, six mono NHC complexes of type NHCAuCl have been synthesized, five of them with yields varying between 41–83%. Finally, compound 19 [AubisNHC]⁺ has been obtained not only by transmetallation, but most gratifyingly through direct metalation in 73% yield. Full article

Background/Objectives: The ability of bacteria to form biofilms makes them more tolerant to traditional antibiotics. Given the lack of new antibiotic development, drug repurposing offers a strategy for discovering new treatments. Auranofin (AF), a gold-based compound indicated for the treatment of rheumatoid arthritis, shows promising antibacterial activity. This study investigates the antimicrobial and antibiofilm activity of AF and its two derivatives in which the thiosugar ligand is replaced by acetylcysteine (AF-AcCys) or naproxen (AF-Napx), against Staphylococcus aureus and Staphylococcus epidermidis. Methods: AF was conjugated by transmetalation with either naproxen or acetylcysteine. Assessments of their stability in DMSO/H₂O and lipophilicity expressed as the LogP were performed. The antimicrobial activity of AF and its analogues were investigated by broth microdilution assay to determine the minimum inhibitory concentration (MIC) and versus biofilm to obtain the minimum bactericidal biofilm concentration (MBBC) and minimum biofilm eradication concentration (MBEC). Results: AF derivatives were found to be stable in a DMSO/H₂O mixture for 48 h. AF-Napx showed a LogP = 1.25 ± 0.22, close to AF, while AF-AcCys had a LogP = −0.95. MIC values of S. aureus and S. epidermidis were ranging from 2 µM to 0.25 µM, and ≤0.12 µM, respectively. Both AF and AF-Napx maintained efficacy against biofilm-embedded S. aureus and S. epidermidis at non-cytotoxic concentrations, with AF-Napx demonstrating lower MBBC values for S. epidermidis. Conclusions: AF, and especially its naproxen conjugate, holds potential as a therapeutic agent for treating biofilm-associated infections caused by S. aureus and S. epidermidis, particularly in device-related infections where both infection and inflammation are present. Full article

Palladium (Pd) is a 4d transition metal with electronic configuration [Kr] 4d¹⁰ 5s⁰, and it is one of the most widely studied metals in the periodic table due to its versatile catalytic role in organic synthesis. The choice of ligands that can coordinate with Pd sites plays a crucial role in the progress of the reaction. Due to the coexistence of multiple oxidation states (Pd(0)/Pd(II)), the active Pd sites of the catalysts can participate in various stages of the coupling reaction. The Pd-catalyzed C-C coupling reactions proceed through four steps: (1) oxidative addition of the reactant to the catalytic site, (2) transmetallation, (3) rearrangements of ligand centers and (4) reductive elimination to the coupling products. For the heterogeneous Pd nanocatalysts, active Pd sites are often strongly bound (chelated) with the solid catalyst surfaces. In this review, we have highlighted the advancements made in the heterogeneous Pd nanocatalysts with an emphasis on the types of different classes of porous solids, which could ligate with the Pd centers via strong covalent bonds. The high specific surface areas and small Pd sites of these nanocatalysts provide a larger number of catalytic sites and thus facilitate the reaction. Mechanistic aspects of the C-C cross-coupling reactions are discussed in the context of the structure–reactivity relationship. Full article

The intrinsic characteristic features of metal–organic frameworks offer unique, great opportunities to develop novel materials with applications in very diverse fields. Aiming to take advantage of these, the application of post-synthetic methodologies has revealed itself to be a powerful approach to the isolation and structuration of metal ions, molecules, or more complex species, either within MOF channels or reticulated at their network, rendering novel and exciting MOFs with new or improved functionalities. Herein, we report the partial post-synthetic metal exchange of Zn(II) metal ions by Co(II) ones in water-stable three-dimensional CaZn₆-MOF 1, derived from the amino acid S-methyl-L-cysteine, allowing us to obtain two novel MOFs with increasing contents of the Co(II) ions Co_4%@1 and Co_8%@1. Remarkably, the presented post-synthetic metal exchange methodology has two relevant implications for us: (i) it allowed us to obtain two novel MOFs, which were not accessible by direct synthesis, and (ii) enabled us to transform physical properties within this family of isoreticular MOFs from the diamagnetic pristine MOF 1 to MOFs Co_4%@1 and Co_8%@1, exhibiting field-induced, frequency-dependent, alternating current magnetic susceptibility signals, which are characteristic features of single-molecule magnets. Full article

1,2-Dihydroisoquinolines are important compounds due to their biological and medicinal activities, and numerous approaches to their synthesis have been reported. Recently, we reported a facile synthesis of trisubstituted allenamides via N-acetylation followed by DBU-promoted isomerization, where various substituted allenamides were conveniently synthesized from readily available propargylamines with high efficiency. In light of this research background, we focused on the utility of this methodology for the synthesis of substituted 1,2-dihydroisoquinolines. In this study, a palladium-catalyzed cascade cyclization–coupling of trisubstituted allenamides containing a bromoaryl moiety with arylboronic acids is described. When N-acetyl diphenyl-substituted trisubstituted allenamide and phenylboronic acid were treated with 10 mol% of Pd(OAc)₂, 20 mol% of P(o-tolyl)₃, and 5 equivalents of NaOH in dioxane/H₂O (4/1) at 80 °C, the reaction proceeded to afford a substituted 1,2-dihydroisoquinoline. The reaction proceeded via intramolecular cyclization, followed by transmetallation with the arylboronic acid of the resulting allylpalladium intermediate. A variety of highly substituted 1,2-dihydroisoquinolines were concisely obtained using this methodology because the allenamides, as reaction substrates, were prepared from readily available propargylamines in one step. Full article

Previously, we demonstrated the synthesis of a well-defined hydroxyalkyl-functionalized N-heterocyclic carbene (NHC)/Ru(II) complex through the transmetalation reaction between [RuCl₂(p-cymene)]₂ and the corresponding NHC/Ag(I) complex derived from a chiral benzimidazolium salt using the Ag₂O method. In this study, we successfully synthesized [RhX(cod)(NHC)] complexes through a one-pot deprotonation route. The hydroxyalkyl-substituted benzimidazolium salt reacted with [Rh(OH)(cod)]₂ in THF at room temperature, affording the corresponding monodentate NHC/Rh(I) complex in nearly quantitative yield. The rhodium complex was characterized using NMR, HRMS measurement, and elemental analysis. Full article

The aromatic character of silolyl and germolyl anions markedly depends on the substituents in the 2,5-positions; carbon-substituted derivatives are nonaromatic, whereas silyl-substituted ones tend to exhibit an aromatic character. However, only carbon-substituted derivatives have been reported for stannolyl anions. In this study, we present the synthesis and structure of a 2,5-disilylated stannolyl anion. Transmetalation of a 2,5-disilyl-1-zirconacyclopentadiene with SnCl₄ gave a dichlorostannole 1, which reacted with potassium tris(trimethylsilyl)silanide to introduce a bulky silyl group on the tin atom. Reduction of the 1-chloro-1-silylstannole 2 with lithium generated the lithium salt of the desired stannolyl anion 3 that adopts an η¹-coordination to the lithium atom. We concluded that the stannolyl anion 3 is nonaromatic based on the pyramidalized tin center and the C–C bond alternation in the five-membered ring as well as the NMR properties. Full article

An unusual series of germylenes and stannylenes stabilized by new tetradentate bis(amidine) ligands RNC(R′)N-linker-NC(R′)NR with a rigid naphthalene backbone has been prepared by protonolysis reaction of Lappert’s metallylenes [M(HMDS)₂] (M = Ge or Sn). Germylenes and stannylenes were fully characterized by NMR spectroscopy and X-ray diffraction analysis. DFT calculations have been performed to clarify the structural and electronic properties associated with tetradentate bis(amidine) ligands. Stannylene L₁Sn shows reactivity through oxidation, oxidative addition, and transmetalation reactions, affording the corresponding gallium and aluminum derivatives. Full article

A novel Eu(tta)₃([4,4′-(t-bu)₂-2,2′-bpy)] complex (tta-thenoyltrifluoroacetone), a ratiometric luminescent-based optical sensor for the quantitative determination of aluminum ion, is synthesized and characterized using XRD and ¹H NMR. The XRD data reveal the slightly distorted octahedral structure. The complex displays a bright red emission at 613 nm in methanol which is characteristic of europium (III) complexes. Upon the addition of Al³⁺ ions, the red emission disappears, and a new blue emission at 398 nm emerges, manifesting the ratiometric nature of the complex. The turn-off of the red emission and turn-on of the blue emission are attributed to Eu-Al trans-metalation, as supported by Raman data that show the emergence of Al-O vibrations at 418, 495, and 608 cm⁻¹ concomitant with the disappearance of Eu-O and Eu-N bond vibrations. Most aluminum sensors are known to suffer from interferences from other metals including Cu²⁺, Co²⁺, and Cd²⁺. However, the sensor reported here is tested for 11 common cations and shows no interference on sensitivity. To the best of our knowledge, this is the first known Eu-based luminescence sensor that successfully exhibited the ability to detect aluminum ions in ppb levels in aqueous environments. The calculated Al³⁺ binding constant is 2.496 × 10³ ± 172. The complex shows a linear relationship in the range of 0–47.6 ppb (1.76 × 10⁻⁶ M) Al³⁺ and the limit of detection (LOD) is 4.79 ppb (1.77 × 10⁻⁷ M) in MeOH. ICP-OES is used for validation of the sensor complex in water and then it was used for quantitative detection of Al³⁺ ions in water as a real-life application. The complex can accurately detect Al³⁺ ions in the range of 4.97–24.9 ppb (1.84 × 10⁻⁷ M–9.2 × 10⁻⁷ M) with an LOD of 8.11 ppb (2.99 × 10⁻⁷ M). Considering that the aluminum ion serves no recognized function within the human body, its accumulation can lead to severe neurological disorders, including Parkinson’s and Alzheimer’s diseases. With the LOD value significantly lower than the WHO-recommended maximum permissible level of 200 ppb for aluminum in drinking water, even without high-power laser-aided signal enhancement, the sensor shows promise for detecting trace amounts of aluminum contamination in water. Therefore, it can significantly aid in the monitoring of even the smallest aluminum ion contamination in drinking water, industrial effluents, and natural water bodies. Full article

Al(III) complexes have been recently investigated for their potential use in imaging with positron emission tomography (PET) by formation of ternary complexes with the radioisotope fluorine-18 (¹⁸F). Although the derivatives of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) are the most applied chelators for [Al¹⁸F]²⁺ labelling and (pre)clinical PET imaging, non-macrocyclic, semi-rigid pentadentate chelators having two N- and three O-donor atoms such as RESCA1 and AMPDA-HB have been proposed with the aim to allow room temperature labelling of temperature-sensitive biomolecules. The paucity of stability data on Al(III) complexes used for PET imaging instigated a complete thermodynamic and kinetic solution study on Al(III) complexes with aminomethylpiperidine (AMP) derivatives AMPTA and AMPDA-HB and the comparison with a RESCA1-like chelator CD3A-Bn (trans-1,2-diaminocyclohexane-N-benzyl-N,N′,N′-triacetic acid). The stability constant of [Al(AMPDA-HB)] is about four orders of magnitude higher than that of [Al(AMPTA)] and [Al(CD3A-Bn)], highlighting the greater affinity of phenolates with respect to acetate O-donors. On the other hand, the kinetic inertness of the complexes, determined by following the Cu²⁺-mediated transmetallation reactions in the 7.5–10.5 pH range, resulted in a spontaneous and hydroxide-assisted dissociation slightly faster for [Al(AMPTA)] than for the other two complexes (t_1/2 = 4.5 h for [Al(AMPTA)], 12.4 h for [Al(AMPDA-HB)], and 24.1 h for [Al(CD3A-Bn)] at pH 7.4 and 25 °C). Finally, the [AlF]²⁺ ternary complexes were prepared and their stability in reconstituted human serum was determined by ¹⁹F NMR experiments. Full article

Serine protease is linked to a wide range of diseases, prompting the development of robust, selective, and sensitive protease assays and sensing methods. However, the clinical needs for serine protease activity imaging have not yet been met, and the efficient in vivo detection and imaging of serine protease remain challenging. Here, we report the development of the gadolinium-cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-click-Sulfonyl Fluoride (Gd-DOTA-click-SF) MRI contrast agent targeting serine protease. The HR-FAB mass spectrum confirmed the successful formation of our designed chelate. The molar longitudinal relaxivity (r₁) of the Gd-DOTA-click-SF probe (r₁ = 6.82 mM⁻¹ s⁻¹) was significantly higher than that of Dotarem (r₁ = 4.63 mM⁻¹ s⁻¹), in the range of 0.01–0.64 mM at 9.4 T. The in vitro cellular study and the transmetallation kinetics study showed that the safety and stability of this probe are comparable to those of conventional Dotarem. Ex vivo abdominal aortic aneurysm (AAA) MRI revealed that this probe has a contrast-agent-to-noise ratio (CNR) that is approximately 51 ± 23 times greater than that of Dotarem. This study of superior visualization of AAA suggests that it has the potential to detect elastase in vivo and supports the feasibility of probing serine protease activity in T1-weighted MRI. Full article

The development of chemosensors able to detect analytes in a variety of sample matrices through a low-cost, fast, and direct approach is of current interest in food, health, industrial, and environmental fields. This contribution presents a simple approach for the selective and sensitive detection of Cu²⁺ ions in aqueous solution based on a transmetalation process of a fluorescent substituted Zn(salmal) complex. Transmetalation is accompanied by relevant optical absorption changes and quenching of the fluorescence emission, leading to high selectivity and sensitivity of the chemosensor, with the advantage of not requiring any sample pretreatment or pH adjustment. Competitive experiments demonstrate a high selectivity of the chemosensor towards Cu²⁺ with respect to the most common metal cations as potential interferents. A limit of detection down to 0.20 μM and a dynamic linear range up to 40 μM are achieved from fluorometric data. By exploiting the fluorescence quenching upon formation of the copper(II) complex, simple paper-based sensor strips, visible to naked eyes under UV light, are used for the rapid, qualitative, and quantitative in situ detection of Cu²⁺ ions in aqueous solution over a wide concentration range, up to 10.0 mM, in specific environments, such as in industrial wastewater, where higher concentrations of Cu²⁺ ions can occur. Full article

A variety of coinage-metal complexes containing perfluorinated carboxylate ligands, together with their structures and thermal behavior, are reported. The silver(I) salts were accessible from the direct reaction of Ag₂O with the acids in toluene. Their gold(I) phosphine counterparts formed in high yields by transmetallation using the silver(I) salts. Some structurally unique, mixed-metal (Au,Ag) complexes formed upon combining solutions of the silver(I) salts with the gold(I) phosphine carboxylates. The reduction of dinuclear copper(II) compounds containing perfluorinated carboxylates with triphenylphosphine resulted in the formation of the corresponding copper(I) tris(phosphine) complexes. X-ray structures of representative complexes, together with IR- and TGA data, are reported. Full article