Tales of the unexpected: The case of zirconium(IV) complexes with desferrioxamine

The Zr4+ complexes with desferrioxamine (H3DFO) and its derivatives are the only 89Zr-based imaging agents for proton emission tomography (PET) that have been used so far in clinical trials. Nevertheless, a complete speciation of the Zr4+/H3DFO system in solution has never been performed and the stability constants of the relevant complexes are still unknown. Here we report, for the first time, the speciation of this system in water, performed by potentiometric titrations, and the determination of the stability constants of all complexes formed in the pH range 2.5–11.5. Surprisingly, although desferrioxamine gives rise to very stable 1:1 complexes with Zr4+ (logK = 36.14 for Zr4+ + DFO3− = [ZrDFO]+), 2:2 and 2:3 ones are also formed in solution. Depending on the conditions, these binuclear complexes can be main species in solution. These results were corroborated by small-angle X-ray scattering (SAXS) and MALDI mass spectrometry analyses of complex solutions. Information on complex structures was obtained by means of density functional theory (DFT) calculations

Supramolecular forces and their interplay in stabilizing complexes of organic anions: tuning binding selectivity in water

How do different supramolecular forces contribute to the stabilization of complexes of organic anions in water? Oftentimes, when debating such a theme, we refer to broad concepts like positive or negative cooperative effects; the focus of the present work is rather on their interplay, i.e. on the way different kinds of stabilizing interactions (salt bridges, H-bonds, anion–π interactions, π–π stacking, solvent effects, etc.) dialogue among themselves. What happens if we tune the strengths of salt bridges by altering the basicity of the anion? What if we change the geometry of the charged group? How does shifting towards more hydrophilic or hydrophobic anions impact the stability of complexes in water? What happens in the solid state? Will aromatic anions go for a π–π stacking or an anion–π interaction mode and do they all behave in the same manner? Does the host/guest size make any difference? What if we play with regiochemistry: will one of the isomers be selectively recognized? Here we present a case study featuring the tetrazine-based ligands L1 and L2 and a series of selected organic anions; potentiometric, NMR, and XRD data and in silico simulations are employed to render such a complex picture.Financial support from the Italian MIUR (project 2015MP34H3) and from the Spanish MINECO (project MAT2014-60104-C2-2-R) is gratefully acknowledged

Crystal engineering of high explosives through lone pair-p interactions: Insights for improving thermal safety

In this high-risk/high-reward study, we prepared complexes of a high explosive anion (picrate) with potentially explosive s-tetrazine-based ligands with the sole purpose of advancing the understanding of one of the weakest supramolecular forces: the lone pair-p interaction. This is a proof-of-concept study showing how lone pair-p contacts can be effectively used in crystal engineering, even of high explosives, and how the supramolecular architecture of the resulting crystalline phases influences their experimental thermokinetic properties. Herein we present XRD structures of 4 novel detonating compounds, all showcasing lone pair-p interactions, their thermal characterization (DSC, TGA), including the correlation of experimental thermokinetic parameters with crystal packing, and in silico explosion properties. This last aspect is relevant for improving the safety of high-energy materials.The financial support provided by the MUR - Dipartimenti di Eccellenza 2023–2027 (DICUS 2.0) to the Department of Chemistry ‘‘Ugo Schiff’’ of the University of Florence is acknowledged

Sensing Zn2+ in aqueous solution with a fluorescent scorpiand macrocyclic ligand decorated with an anthracene bearing tail

Synthesis of the new scorpiand ligand L composed of a [9]aneN3 macrocyclic ring bearing a CH2CH2NHCH2-anthracene tail is reported. L forms both cation (Zn2+) and anion (phosphate, benzoate) complexes. In addition, the zinc complexes of L bind these anions. The equilibrium constants for ligand protonation and complex formation were determined in 0.1 M NaCl aqueous solution at 298.1 ± 0.1 K by means of potentiometric (pH-metric) titrations. pH Controlled coordination/detachment of the ligand tail to Zn2+ switch on and off the fluorescence emission from the anthracene fluorophore. Accordingly, L is able to sense Zn2+ in the pH range 6–10 down to nM concentrations of the metal ion. L can efficiently sense Zn2+ even in the presence of large excess of coordinating anions, such as cyanide, sulphide, phosphate and benzoate, despite their ability to bind the metal ion

Anion-π and lone pair-π interactions with s-tetrazine-based ligands

Most of traditional and contemporary interest in s-tetrazine derivatives focuses onto their redox properties, reactivity and energy density. In recent times, however, an increasing number of reports highlighted the possible usefulness of the s-tetrazine moiety as a binding site for anionic and electron rich species, according to the high and positive quadrupolar moment of this heterocycle and the consequent strength of anion-π and lone pair-π interactions. Herein, after giving a quick perspective on s-tetrazine properties and on how they foster these types of π interactions, we present statistical and critical examination of the available structural data, doing justice to the debated topic of the existence and directionality of anion- and lone pair-π interactions. Finally, available literature material concerning the usage of s-tetrazine as supramolecular binding site in solution, i.e. paving the way to applications such as molecular recognition and sensing, is presented and discussed.Financial support from the Spanish MINECO (project MAT2014- 60104-C2-2-R) and MCIU (RTI2018-101558-B-C21) and from Italian MIUR (project 2015MP34H3) are gratefully acknowledged

Halide and hydroxide anion binding in water

The formation of halide and hydroxide anion complexes with two ligands L1 (3,6-bis(morpholin-4- ylmethyl)-1,2,4,5-tetrazine) and L2 (3,6-bis(morpholin-4-ylethyl)-1,2,4,5-tetrazine) was studied in aqueous solution, by means of potentiometric and ITC procedures. In the solid state, HF2 −, Cl− and Br− complexes of H2L22+ were analysed by single crystal XRD measurements. Further information on the latter was obtained with the use of density functional theory (DFT) calculations in combination with the polarizable continuum model (PCM). The presence of two halide or bifluoride HF2 − (F–H–F−) anions forming anion–π interactions, respectively above and below the ligand tetrazine ring, is the leitmotiv of the [(H2L2)X2] (X = HF2, Cl, Br, I) complexes in the solid state, while hydrogen bonding between the anions and protonated morpholine ligand groups contributes to strengthen the anion–ligand interaction, in particular in the case of Cl− and Br−. In contrast to the solid state, only the anion : ligand complexes of 1 : 1 stoichiometry were found in solution. The stability of these complexes displays the peculiar trend I− > F− > Br− > Cl− which was rationalized in terms of electrostatic, hydrogen bond, anion–π interactions and solvent effects. DFT calculations performed on [(H2L2)X]+ (X = F, Cl, Br, I) in PCM water suggested that the ligand assumes a U-shaped conformation to form one anion–π and two salt bridge interactions with the included anions and furnished structural information to interpret the solvation effects affecting complex formation. The formation of hydroxide anion complexes with neutral (not protonated) L1 and L2 molecules represents an unprecedented case in water. The stability of the [L(OH)]− (L = L1, L2) complexes is comparable to or higher than the stability of halide complexes with protonated ligand molecules, their formation being promoted by largely favourable enthalpic contributions that prevail over unfavourable entropic changes.Financial support from the Italian MIUR (project 2015MP34H3) and from the Spanish MINECO (project MAT2014-60104-C2-2-R) is gratefully acknowledged. The centre of instrumental facilities, STI, of the University of Jaén is acknowledged for technical assistance. FP acknowledges the Department of Applied Chemistry of the Graduate School of Engineering of Tohoku University for financial support