Metal-ligand Binding Research Articles

Exploring Interatomic Electron Transfer and Metal-Ligand Binding Mechanism in Trimethylenemethane Iron Tricarbonyl: Insights from Potentials per Electron and Corresponding Force Density Fields.

This study employs an analysis of the per-electron potentials and the superposition of the electrostatic and kinetic force fields, Fes(r) and Fk(r), and the gradients of the potential energy and one-electron densities to investigate the binding mechanism in trimethylenemethane iron tricarbonyl complex (TMM)Fe(CO)3. Our approach permits the delineation of the "ligand-binding" force field generated by the metal nucleus but partially operating within the ligand atoms. A mechanical rationale for metal-ligand interactions is thus presented: In the corresponding area, the attractive force Fes(r) provides the backdrop against which the homotropic static force (r) and the heterotropic kinetic force Fk(r) exert attractive and repulsive influences, respectively, toward the metal nucleus on a portion of the electrons belonging to the ligand atoms. This area thus represents electron sharing, which emerges as a quantum chemical response against the metal-to-ligand electron transfer. It has been demonstrated that the response is facilitated by the decreased potential energy density in the vicinity of the interatomic surface. Our findings indicate that the polar coordination bonds in (TMM)Fe(CO)3 exhibit notable quantum chemical responses. However, the previously described nonbonded contact also features an unexpectedly pronounced response, despite the absence of a bond path. It can be proposed that the unforeseen response is a consequence of the formation of the 18-electron, closed valence shell, rather than an indication of the establishment of an organometallic chemical bond.

Single-Atom Catalysts through Pressure-Controlled Metal Diffusion.

Single-atom catalysts (SACs) open up new possibilities for advanced technologies. However, a major complication in preparing high-density single-atom sites is the aggregation of single atoms into clusters. This complication stems from the delicate balance between the diffusion and stabilization of metal atoms during pyrolysis. Here, we present pressure-controlled metal diffusion as a new concept for fabricating ultra-high-density SACs. Reducing the pressure inhibits aggregation substantially, resulting in almost three times higher single-atom loadings than those obtained at ambient pressure. Molecular dynamics and computational fluid dynamics simulations reveal the role of a metal hopping mechanism, maximizing the metal atom distribution through an increased probability of metal-ligand binding. The investigation of the active site density by electrocatalytic oxygen reduction validates the robustness of our approach. The first realization of Ullmann-type carbon-oxygen couplings catalyzed on single Cu sites demonstrates further options for efficient heterogeneous catalysis.

Mining for Metal-Organic Systems: Chemistry Frontiers of Th-, U-, and Zr-Materials.

The conceptual framework presented in this Perspective overviews the design principles of innovative thorium-based materials that could address urgent needs of the medicinal, nuclear energy, and waste remediation sectors from the lens of zirconium and uranium analogs. We survey the intersections of Zr, Th, and U chemistry with a focus on how the intrinsic behavior of each metal translates to broader material properties, including, but not limited to, structural and topological diversity, preferential metal-ligand binding, and reactivity. On the example of several classes of materials, including organometallic complexes, polyoxometalates, and the primary focus of this Perspective, metal-organic frameworks (MOFs), the design principles that govern the preparation of Zr-, Th-, and U-compounds, including oxophilicity, variation in oxidation states, and stable coordination environments have been considered. Further, we highlight how the impact of the mentioned variables may shift throughout the progression from discrete molecular systems to extended structures. We discuss the common assumption that zirconium-organic materials are typically considered a close analog of thorium-based congeners in areas such as material design and preparation. Through consideration of fundamental chemistry principles, we shed light on the relationships between Zr-, Th-, and U-based materials and highlight how a critical analysis of their distinct properties can be used to target a desired material performance. As a result, we provide a detailed understanding of Th-based materials chemistry by anchoring their fundamental properties between two well-studied reference points, zirconium- and uranium-containing analogs.

Synthesis, Characterization, and Cytotoxicity of a Ga(III) Complex with Warfarin

The gallium(III) complex of warfarin was synthesized, and its structure was determined by means of theoretical, analytical, and spectral analyses. Significant differences in the IR and Raman spectra of the complex were observed as compared to the spectra of the ligand and confirmed the suggested metal-ligand binding mode. The theoretical study of the Ga(III) complex of warfarin has been done to elucidate the structure-activity relation, inter- and intra-molecular interactions, and frontier molecular orbital energy analysis based on DFT computations. A molecular docking study has been performed to predict the biological activity of the molecule. In this paper, we report preliminary results about the cytotoxicity of the investigated compounds. The cytotoxic effects of the ligand and its Ga(III) complex were determined using the MTT method on different tumor cell lines. The screening performed revealed that the tested compounds exerted cytotoxic activity on the evaluated cell lines.

Synthesis, characterization, biological potency, and molecular docking of Co2+, Ni2+ and Cu2+ complexes of a benzoyl isothiocyanate based ligand

The primary objective of the present study was to produce metal complexes of H4DAP ligand (N,N'-((pyridine-2,6-diylbis(azanediyl))bis(carbonothioyl))dibenzamide) derived from 2,6-diaminopyridine and benzoyl isothiocyanate with either ML or M2L stoichiometry. There are three distinct coordination complexes obtained with the formulas [Co(H2DAP)]·H2O, [Ni2(H2DAP)Cl2(H2O)2]·H2O, and [Cu(H4DAP)Cl2]·3H2O. The confirmation of the structures of all derivatives was achieved through the utilization of several analytical techniques, including FT-IR, UV–Vis, NMR, GC–MS, PXRD, SEM, TEM analysis, and QM calculations. Aiming to analyze various noncovalent interactions, topological methods such as QTAIM, NCI, ELF, and LOL were performed. Furthermore, the capacity of metal–ligand binding was examined by fluorescence emission spectroscopy. An in vitro investigation showed that the viability of MDA-MB-231 and HepG-2 cells was lower when exposed to the manufactured Cu2+ complex, in comparison to the normal cis-platin medication. The compounds were further evaluated for their in vitro antibacterial activity. The Ni2+ complex has shown promising activity against all tested pathogens, comparable to the reference drugs Gentamycin and Ketoconazole. Furthermore, a computational docking investigation was conducted to further examine the orientation, interaction, and conformation of the recently created compounds on the active site of the Bcl-2 protein.

Prediction of stability constants of metal-ligand complexes by machine learning for the design of ligands with optimal metal ion selectivity.

The new LOGKPREDICT program integrates HostDesigner molecular design software with the machine learning (ML) program Chemprop. By supplying HostDesigner with predicted logK values, LOGKPREDICT enhances the computer-aided molecular design process by ranking ligands directly by metal-ligand binding strength. Harnessing reliable experimental data from a historic National Institute of Standards and Technology (NIST) database and data from the International Union of Pure and Applied Chemistry (IUPAC), we train message passing neural net algorithms. The multi-metal NIST-based ML model has a root mean square error (RMSE) of 0.629 ± 0.044 (R2 of 0.960 ± 0.006), while two versions of lanthanide-only IUPAC-based ML models have, respectively, RMSE of 0.764 ± 0.073 (R2 of 0.976 ± 0.005) and 0.757 ± 0.071 (R2 of 0.959 ± 0.007). For relative logK predictions on an out-of-sample set of six ligands, demonstrating metal ion selectivity, the RMSE value reaches a commendably low 0.25. We showcase the use of LOGKPREDICT in identifying ligands with high selectivity for lanthanides in aqueous solutions, a finding supported by recent experimental evidence. We also predict new ligands yet to be verified experimentally. Therefore, our ML models implemented through LOGKPREDICT and interfaced with the ligand design software HostDesigner pave the way for designing new ligands with predetermined selectivity for competing metal ions in an aqueous solution.

Infrared Spectroscopy of [M(CO2)n]+ (M = Ca, Sr, and Ba; n = 1-4) in the Gas Phase: Solvation-Induced Electron Transfer and Activation of CO2.

Cationic complexes of heavy alkaline earth metal and carbon dioxide [M(CO2)n]+ (M = Ca, Sr, and Ba) are produced by a laser vaporization-supersonic expansion ion source in the gas phase and are studied by infrared photodissociation spectroscopy in conjunction with quantum chemistry calculations. For the n = 1 complexes, the metal-ligand binding arises primarily from the electrostatic interaction with the CO2 ligand bound to the metal (+I) center in an end-on η1-O fashion. The more highly coordinated complexes [M(CO2)n]+ with n ≥ 2 are characterized to involve a [M2+(CO2-)] core ion with the CO2- ligand bound to the metal (+II) center in a bidentate η2-O, O manner. The activation of CO2 in forming a bent CO2- moiety occurs via solvation-induced metal cation-ligand electron transfer reactions. Bonding analyses reveal that the attractive forces between M2+ and CO2- in the core cation come mainly from electrostatic attraction, but the contribution of covalent orbital interactions should not be underestimated. The atomic orbitals of metal dications that are engaged in the orbital interactions are ns and (n - 1)d orbitals.

Degradation and Erosion of Metal-Organic Frameworks: Comparative Study of a NanoMIL-100 Drug Delivery System.

To make a drug work better, the active substance can be incorporated into a vehicle for optimal protection and control of the drug delivery time and space. For making the drug carrier, the porous metal-organic framework (MOF) can offer high drug-loading capacity and various designs for effective drug delivery performance, biocompatibility, and biodegradability. Nevertheless, its degradation process is complex and not easily predictable, and the toxicity concern related to the MOF degradation products remains a challenge for their clinical translation. Here, we describe an in-depth molecular and nanoscale degradation mechanism of aluminum- and iron-based nanoMIL-100 materials exposed to phosphate-buffered saline. Using a combination of analytical tools, including X-ray photoelectron spectroscopy, nuclear magnetic resonance spectroscopy, small-angle X-ray scattering, and electron microscopy, we demonstrate qualitatively and quantitatively the formation of a new coordination bond between metal(III) and phosphate, trimesate release, and correlation between these two processes. Moreover, the extent of material erosion, i.e., bulk or surface erosion, was examined from the transformation of nanoparticles' surface, morphology, and interaction with water. Similar analyses show the impact of drug loading and surface coating on nanoMIL-100 degradation and drug release as a function of the metal-ligand binding strength. Our results indicate how the chemistry of nanoMIL-100(Al) and nanoMIL-100(Fe) drug carriers affects their degradation behaviors in a simulated physiological medium. This difference in behavior between the two nanoMIL-100s enables us to better correlate the nanoscale and atomic-scale mechanisms of the observed phenomena, thus validating the presented multiscale approach.

Quantitative measurement of cation-mediated adhesion of DNA to anionic surfaces.

Anionic polyelectrolytes, such as DNA, are attracted to anionic surfaces in the presence of multivalent cations. A major barrier toward molecular-level understanding of these attractive interactions is the paucity of measurements of the binding strength. Here, atomic force microscopy-based single molecule force spectroscopy was used to quantify the binding free energy of double-stranded DNA to an anionic surface, with complementary density functional theory calculations of the binding energies of metal ion-ligand complexes. The results support both electrostatic attraction and ion-specific binding. Our study suggests that the correlated interactions between counterions are responsible for attraction between DNA and an anionic surface, but the strength of this attraction is modulated by the identity of the metal ion. We propose a mechanism in which the strength of metal-ligand binding, as well as the preference for particular binding sites, influence both the concentration dependence and the strength of the DNA-surface interactions.

Three derivatives of phenacyldiphenylphosphine oxide: influence of aromatic and alkyl substituents on the luminescence sensitization of four Ln(NO3)3 salts.

A series of four β-carbonylphosphine oxide compounds have been synthesized, and their complexes with the nitrate salts of Sm3+, Eu3+, Tb3+ and Dy3+ have been characterized in solution and in the solid state. Analysis of the complexes using IR and NMR suggests that metal-ligand binding occurs mainly through the phosphine oxide group of the ligand, with some involvement of the carbonyl group. All 16 complexes luminesce in solutions of acetonitrile, albeit with varying degrees of intensity. The highest quantum yield values obtained for this series are those where the ligand contains an aryl carbonyl group paired with an electron rich phosphine oxide group (29.8 and 11% for the Tb3+ and Eu3+ complexes, respectively). In contrast, the longest emission lifetime values were found for complexes where the ligand contains a bulky substituent on the carbonyl group paired with an electron rich phosphine oxide (1.86, 1.402, 0.045 ms for the Tb3+, Eu3+ and Sm3+ complexes, respectively).

Indole-based Fluorometric and Colorimetric Chemosensors for the Selective Detection of Cu2+: A Brief Review From the Year 2011-2021

The development of chemosensors has been driven by concurrently advanced research in fluorescence and colorimetric chemosensing. Over the last few decades, the development of copper ion-selective fluorogenic and chromogenic chemosensors has been extensively studied due to their high sensitivity, low cost, and simplicity. They can interact with the metal ion in a unique manner and create measurable color, fluorescence, or redox potential changes. Copper (Cu2+) ion is deemed the third most prevalent transition metal in human beings owing to its various biological and physiological processes. It has drawn a great deal of attention from many researchers in various disciplines such as biology, medicine, and environmental studies. However, an excessive buildup of copper in the body has been linked to several diseases. Thus, more recent research is being focused on developing fluorometric and colorimetric chemosensors for the selective detection of copper ions. Recently, there have been a lot of studies reported in this field of study that describe highly sensitive and sophisticated indole-based chemosensors for various metal ions of interest. In addition, indole derivatives possess inherent fluorescence properties due to their electron-rich nature caused by the π-excessive system of indole, and therefore they can be employed in chemosensors for metal ion detection. Both cations and anions employ it as a molecular recognition system. This review summarizes selective and sensitive Cu2+ ion detection accomplished byvarious indole-based chemosensors between the years 2011 to 2021. Furthermore, sensor design, sensing methods, ligand-metal binding stoichiometry, association constant, and the detection limit by the chemosensors are all summarized and explored.
 Keywords: Indole, Fluorescent chemosensors, Colorimetric chemosensors, Cu2+, Turn-on, Turn-off

Ligand-Aided Glycolysis of PET Using Functionalized Silica-Supported Fe2O3 Nanoparticles.

The development of efficient catalysts for the chemical recycling of poly(ethylene terephthalate) (PET) is essential to tackling the global issue of plastic waste. There has been intense interest in heterogeneous catalysts as a sustainable catalyst system for PET depolymerization, having the advantage of easy separation and reuse after the reaction. In this work, we explore heterogeneous catalyst design by comparing metal-ion (Fe3+) and metal-oxide nanoparticle (Fe2O3 NP) catalysts immobilized on mesoporous silica (SiO2) functionalized with different N-containing amine ligands. Quantitative solid-state nuclear magnetic resonance (NMR) spectroscopy confirms successful grafting and elucidates the bonding mode of the organic ligands on the SiO2 surface. The surface amine ligands act as organocatalysts, enhancing the catalytic activity of the active metal species. The Fe2O3 NP catalysts in the presence of organic ligands outperform bare Fe2O3 NPs, Fe3+-ion-immobilized catalysts and homogeneous FeCl3 salts, with equivalent Fe loading. X-ray photoelectron spectroscopy analysis indicates charge transfer between the amine ligands and Fe2O3 NPs and the electron-donating ability of the N groups and hydrogen bonding may also play a role in the higher performance of the amine-ligand-assisted Fe2O3 NP catalysts. Density functional theory (DFT) calculations also reveal that the reactivity of the ion-immobilized catalysts is strongly correlated to the ligand-metal binding energy and that the products in the glycolysis reaction catalyzed by the NP catalysts are stabilized, showing a significant exergonic character compared to single ion-immobilized Fe3+ ions.

Interplay between different metal–ligand binding modes in tin(II) complexes with pyridine

In this work, the π-complexation interaction between simple tin(II) molecules SnX2 (X = H, F, Cl, Br, I) and the π-cloud of pyridine (py) in a series of their model complexes SnX2·py was characterized using a variety of quantum chemical methods. Moreover, the coexistence of this interaction and the well-known σ-complexation interaction between the lone pair on the N atom of py and another SnX2 molecule was studied in the corresponding series of model complexes SnX2·py·SnX2. The interplay between the two metal–ligand binding modes was established in terms of structural changes, interaction energies, interaction energy components and topological electron density parameters. The interaction between SnX2 and py in their SnX2·py π-complexes is weak and its strength is further diminished by the σ-complexation of another SnX2 molecule, forming the SnX2·py·SnX2 complexes. The weakening is in fact mutual yet the strength of the σ-complexation interaction is reduced only marginally.

Green-emitting functionalized silicon nanoparticles as an “off-on” fluorescence bio-probe for the sensitive and selective detection of mercury (II) and 3-mercaptopropionic acid

Herein, we developed a class of functionalized silicon nanoparticles (F-SiNPs) bio-probes named thiol-conjugated F-SiNPs. They combine excellent biocompatibility with small dimensions (<10 nm) and biological usefulness with sustained and robust fluorescence (3.32% photoluminescent quantum yield). Identifying 3-Mercaptopropionic acid (3-MPA), which lowers the quantity of gamma-aminobutyric acid in the brain, and mercury (Hg2+) was a crucially important step since their excessive levels are a sign of several disorders. Using F-SiNPs as a fluorescent bio-probe, we provided an “off-on” technique for sensitively and selectively determining Hg2+ and 3-MPA in this study. The 3-(2-aminoethylamino) propyl (dimethoxymethylsilane) and basic fuchsin as precursors were hydrothermally treated to produce the F-SiNPs exhibiting green fluorescence. Our results suggest that Hg2+ reduced the fluorescence of F-SiNPs because of strong ionic interactions and metal-ligand binding among many thiols and carboxyl groupings at the surface of Hg2+ and F-SiNPs. Additionally, the resultants demonstrated that after being quenched by Hg2+, the produced F-SiNPs led to the distinctive “off-on” response to 3-MPA. Moreover, the method could detect Hg2+ and 3-MPA with limits of detection of 0.065 μM and 0.017 μM, respectively. The technique employed is quick, easy, affordable, and environmentally friendly. The sensing platform has successfully determined Hg2+ and 3-MPA in urine, water, and human serum samples.

Platinum(II) terpyridine-based supramolecular polymer gels with induced chirality.

Metal-ligand binding plays a crucial role in regulating the photophysical properties of supramolecular gels. In this study, we designed 1-Pt complexes comprising a central benzene-1,3,5-tricarboxamide unit functionalized with three terpyridines, which can form supramolecular gels with Pt(II). The resulting supramolecular gel of 1-Pt exhibited strong orange emission, which was attributed to the metal-to-metal ligand charge transfer during gel formation. Furthermore, the temperature-dependent absorption spectrum changes of the supramolecular polymer 1-Pt exhibited a nonsigmoidal transition, following a cooperative pathway involving a nucleation-elongation mechanism. Additionally, the strategy for the co-assembling system involving 1-Pt with chiral molecules (D-form and L-form) induced the helical arrangement of 1-Ptvia chiral additives in supramolecular metallogels.

Benchmarking biomolecular force field-based Zn2+ for mono- and bimetallic ligand binding sites.

Zn2+ is one of the most versatile biologically available metal ions, but accurate modeling of Zn2+ -containing metalloproteins at the biomolecular force field level can be challenging. Since most Zn2+ models are parameterized in bulk solvent, in-depth knowledge about their performance in a protein environment is limited. Thus, we systematically investigate here the behavior of non-polarizable Zn2+ models for their ability to reproduce experimentally determined metal coordination and ligand binding in metalloproteins. The benchmarking is performed in challenging environments, including mono- (carbonic anhydrase II) and bimetallic (metallo-β-lactamase VIM-2) ligand binding sites. We identify key differences in the performance between the Zn2+ models with regard to the preferred ligating atoms (charged/non-charged), attraction of water molecules, and the preferred coordination geometry. Based on these results, we suggest suitable simulation conditions for varying Zn2+ site geometries that could guide the further development of biomolecular Zn2+ models.

CuAAC-Derived Selective Fluorescent Probe as a Recognition Agent for Pb(II) and Hg(II): DFT and Docking Studies.

Copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) is a resourceful and stereospecific methodology that has considerably yielded promising 1,2,3-triazole-appended "click" scaffolds with the potential for selective metal ion recognition. Based on "click" methodology, this report presents a chemosensor probe (TCT) based on 4-tert-butylcatechol architecture, via the CuAAC pathway, as a selective and efficient sensor for Pb(II) and Hg(II) ions, categorized as the most toxic and alarming environmental contaminants among the heavy metal ions. The synthesized probe was successfully characterized by spectroscopy [IR and NMR (1H and 13C)] and mass spectrometry. The chemosensing study performed in acetonitrile/water (4:1) solvent media, via UV-vis and fluorescence spectroscopy, established its selective sensitivity for Pb(II) and Hg(II) species among the list of explored metal ions with the limits of detection being 8.6 and 11 μM, respectively. Additionally, the 1H NMR and IR spectra of the synthesized TCT-metal complex also confirmed the metal-ligand binding. Besides, the effect of time and temperature on the binding ability of TCT with Pb(II) and Hg(II) was also studied via UV-vis spectroscopy. Furthermore, density functional theory studies put forward the structural comprehension of the sensor by availing the hybrid density functional (B3LYP)/6311G++(d,p) basis set of theory which was subsequently utilized for investigating its anti-inflammatory potential by performing docking analysis with human leukotriene b4 protein.

Mechanistic study of Hg(II) interaction with three different α-aminophosphonate adsorbents: Insights from batch experiments and theoretical calculations.

Herein, efficient and potential chelating α-aminophosphonate based sorbents (AP-) derived from three different amine origins (aniline/anthranilic acid/O-phenylenediamine) to form AP-H, carboxylated and aminated enhanced aminophosphonate as AP-H, AP-COOH, and AP-NH2 were synthesized via a facile method. The structure of the synthesized sorbents was elucidated using different techniques; elemental analysis (CHNP/O), FT-IR, NMR (1H-, 13C and 31P NMR), TGA and BET. The fabricated sorbents were exploited for Hg(II) removal from aqueous solution via sorption properties. Isotherm fitted by Langmuir equation: the maximum sorption capacities at optimum pH 5.5, and T:25±1°C, were found to be 1.33, 1.23, and 1.15mmol Hg g-1 for AP-COOH, AP-NH2, AP-H, respectively, which is roughly correlated with the active sites density and the hard/soft characteristics of adsorbents' reactive groups. Metal-ligand binding affinities are qualitatively rationalized in terms of hard and soft acids and bases (HSAB) theory. The interaction of Hg(II) (soft) has a stronger affinity to AP-COOH can be considered a softer base compared with reference material (AP-H) over than AP-NH2 (hard). This sequence result showed opposite trends consistent with their reciprocal properties according to the steric effect modulates and the specific surface area. Thermodynamics analysis for absolute values of ΔH°, ΔS° and ΔG° afford the selectivity towards Hg(II) sorption with the following order: AP-COOH>AP-NH2 >AP-H. Elution and regeneration was carried out by HCl solution and recycled for a minimum of five cycles, the sorption and desorption efficiencies are greater than 91%. Such sorbents exhibit good durability, stability and promising potential for Hg(II) removal. Finally, a new modelling technique for quantitative non-linear description and comparison of equivalent geographical positions in 3D space of extended relationships. Exothermic and spontaneous behavior were observed using a proposed Floatotherm that included the Van't Hoff parameters model.

Synthesis and Chemosensory Properties of New Cyanosubstituted 2,2'-Bipyridine Derivatives

A series of novel 6-oxo-1,6-dihydro-[2,2'-bipyridine]-5-carbonitriles has been synthesized and characterized. Their photophysical properties in DMSO solution and aqueous medium as well as fluorescence response to the presence of metal ions have been investigated. The obtained 4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-[2,2'-bipyridine]-5-carbonitrile has been shown as a selective fluorescent "turn-ON" probe for Cd2+ ions with LoD 0.359µM, 1:1 metal-ligand ratio and binding constant of 5.2 × 104M-1.

Peroxide-Selective Reduction of O2 at Redox-Inactive Rare-Earth(III) Triflates Generates an Ambiphilic Peroxide.

Metal peroxides are key species involved in a range of critical biological and synthetic processes. Rare-earth (group III and the lanthanides; Sc, Y, La-Lu) peroxides have been implicated as reactive intermediates in catalysis; however, reactivity studies of isolated, structurally characterized rare-earth peroxides have been limited. Herein, we report the peroxide-selective (93-99% O22-) reduction of dioxygen (O2) at redox-inactive rare-earth triflates in methanol using a mild metallocene reductant, decamethylferrocene (Fc*). The first molecular praseodymium peroxide ([PrIII2(O22-)(18C6)2(EG)2][OTf]4; 18C6 = 18-crown-6, EG = ethylene glycol, -OTf = -O3SCF3; 2-Pr) was isolated and characterized by single-crystal X-ray diffraction, Raman spectroscopy, and NMR spectroscopy. 2-Pr displays high thermal stability (120 °C, 50 mTorr), is protonated by mild organic acids [pKa1(MeOH) = 5.09 ± 0.23], and engages in electrophilic (e.g., oxygen atom transfer) and nucleophilic (e.g., phosphate-ester cleavage) reactivity. Our mechanistic studies reveal that the rate of oxygen reduction is dictated by metal-ion accessibility, rather than Lewis acidity, and suggest new opportunities for differentiated reactivity of redox-inactive metal ions by leveraging weak metal-ligand binding events preceding electron transfer.