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89Zr−immunoPET is a hot topic as 89Zr cumulates the advantages of 64Cu and 124I without their drawbacks. We report the synthesis of a model ligand of a chiral bioconjugable tetrahydroxamic chelator combining the desferriferrioxamine B siderophore and 1‐hydroxy‐2‐piperidone ((PIPO)H), a chiral cyclic hydroxamic acid derivative, and the study by NMR spectroscopy of its zirconium complex. Nuclear Overhauser effect measurements (ROESY) indicated that the complex exists in the form of two diastereomers, in 77 : 23 ratio, resulting from the combination of the central chiralities at the 3‐C of the (PIPO)H component and at the Zr4+ cation. The 44 lowest energy structures out of more than 1000 configurations/conformations returned by calculations based on density functional theory were examined. Comparison of the ROESY data and the calculated interatomic H⋅⋅⋅H distances allowed us to select the most probable configuration and conformations of the major complex. [ABSTRACT FROM AUTHOR]

Two different alkynyl-substituted C3-symmetric cyclotribenzylenes (CTB) were synthesized in racemic and enantiomerically pure forms, and six gold(I) phosphine complexes differing by the nature of the CTB and the phosphine were prepared and characterized, in particular by NMR spectroscopy, DOSY, electronic circular dichroism (ECD), and electrospray ionization mass spectrometry (ESI-MS). Their ECD patterns depended on the substitution of the starting CTBs and were shifted bathochromically by comparison with the latter. ESI-MS in the presence of HCO2H allowed us to detect the complexes as proton adducts. The intensities of the signals were stronger when the phosphine was more electron-rich. This technique was also used to investigate the exchange of phosphine betweeen pairs of CTB complexes. The scrambling reaction was demonstrated by the higher intensity of the signals of the complexes subjected to the exchange of a single phosphine ligand by comparison with the intensity of the signals of the starting complexes. [ABSTRACT FROM AUTHOR]

A series of tetraaza‐expanded calix[4]arene analogues (2–4), in which two of the four aryl groups are ethylene‐protected thiophenol components were prepared from tetraaldehyde 1. Two of these strapped macrocycles were characterized crystallographically, as well as the dipalladium complex of 4. The same tetraaldehyde had been previously used for the synthesis of a macrotricycle (5) and a macropentacycle (6), the coordination properties of which have been investigated. In particular, ligand 6 was shown to be able to encapsulate a Cu+ or a Ag+ ion in the tetrahedral coordination pocket offered by a bridgehead nitrogen atom and the three proximal thioether sulfur atoms. [ABSTRACT FROM AUTHOR]

Cyclotribenzylenes (CTBs) combining carbonitrile (−CN) and alkyne (−C2H) substituents were synthesized as racemic mixtures and resolved by HPLC on chiral stationary phases. Two of these compounds were used to prepare platinum‐bridged CTB dimers, in which PtII is bound to the CTBs via Pt−alkynyl bonds in cis configuration. The organometallic complexes were examined by mass spectrometry and NMR spectroscopy, which indicated that they were obtained as mixtures of diastereoisomers (a meso or syn form and a pair of chiral or anti forms) when racemic CTBs were used. Enantiomerically pure complexes were prepared from resolved CTBs, which allowed us to distinguish the NMR signals of the chiral and meso forms in the diastereoisomeric mixtures. In certain conditions, the platinum complexes played the role of a pincer π‐alkynyl ligand for Cu(I) coming from the copper iodide used as a synthetic auxiliary. The Cu+ cations could be easily removed by treatment with NaCN, affording the mononuclear bis‐cyclotribenzylene complexes. These compounds failed to lead to metallo‐cryptophanes by coordination of two [M(dppp)]2+ complex subunits (M=Pd, Pt; dppp=1,3‐bis(diphenylphosphino)propane), each to two carbonitrile substituents belonging to different CTBs, pointing to the superiority of the one pot self‐assembly processes for the preparation of metallo‐cryptophanes. [ABSTRACT FROM AUTHOR]

This paper presents the characterization of a novel solid-phase sorbent for iron(III) and zirconium(IV) obtained by the functionalization of a commercial epoxy methacrylate resin (Purolite® ECR8209) with desferrioxamine B (DFO). The sorption properties of the solid material, named DFO@Purolite, towards Fe(III) and Zr(IV) were investigated in detail. In particular, the sorption kinetics, isotherms and sorption profiles as a function of the solution's pH were studied. The stoichiometry and the complexation constants of both cations with the active sites of the sorbent were determined by applying the Gibbs–Donnan model, i.e., the model used to explain the protonation and the metal sorption on ion exchange resins. While the chelating properties of the solid material investigated herein are in good agreement with those of Fe(III)/DFO and Zr(IV)/DFO previously determined in homogeneous aqueous solutions, the solid/liquid extraction studies further allow to ascertain the speciation model for the latter system that is still subjected to controversy in the literature. [ABSTRACT FROM AUTHOR]

Six‐ and seven‐membered cyclic hydroxamic acids are found as terminal binding units in different families of siderophores, including exochelins and mycobactins. The simplest models of these preorganized chelating ligands were known, but their coordination chemistry with Fe3+, the target metal ion of siderophores, had never been reported. Four complexes were synthesized and studied: two Fe3+ complexes, one with the six‐membered ring hydroxamate PIPO− and one with the seven‐membered ring hydroxamate AZEPO−, and the two corresponding Ga3+ complexes. X‐ray diffraction studies showed that the interligand repulsion energies were better minimized in the case of the AZEPO− complexes whatever the metal cation considered, and that the Fe−O bond distances were shorter in [Fe(AZEPO)3] by comparison with [Fe(PIPO)3]. [ABSTRACT FROM AUTHOR]

This article covers 50 years of coordination chemistry of transition metal complexes and metal‐sulfur aggregates involving thiolate‐incorporating ligands by reviewing selected examples. The studies in the coordination chemistry of sulfur‐rich ligands have been undoubtedly triggered and fed by the concomitant development of bioinorganic chemistry, particularly of iron‐sulfur enzymes. The review is broken down in five sections, which examine complexes of increasing nuclearity, including binuclear complexes based on compartmental macrocyclic ligands. We show also how ligand engineering has allowed the researchers in the field to control the nuclearity of the complexes, which was a particularly difficult task for sulfur‐based ligands, as thiolates show a strong tendency to coordinate to more than one metal cation at once. [ABSTRACT FROM AUTHOR]

The syntheses and properties of expanded 4‐tert‐butyl‐mercaptocalix[4]arenes, in which the methylene linkers are replaced by −CH2NRCH2− or −CH2NRCH2− and −CH2NRCH2CH2CH2NRCH2− units, are described. The new macrocycles were obtained in a step‐wise manner, utilizing fully protected, i. e. S‐alkylated, derivatives of the oxidation‐sensitive thiophenols in the cyclisation steps. Reductive cleavage of the macrobicyclic or macrotricyclic intermediates (6, 7, 11) afforded the free thiophenols (H48, H49, and H412) in preparative yields as their hydrochloride salts. The protected proligands can exist in two conformations, resembling the "cone" and "1,3‐alternate" conformations found for the parent calix[4]arenes. The free macrocycles do not show conformational isomerism, but are readily oxidized forming intramolecular disulfide linkages. Preliminary complexation experiments show that these expanded mercaptocalixarenes can serve as supporting ligands for tetranuclear thiolato clusters. [ABSTRACT FROM AUTHOR]

Chiral gold(I) acetylide trinuclear complexes 1–3 based on the cyclotribenzylene platform and terminal PR3 ligands (R=Ph, Et, and Cy, respectively), were characterized and their light emission studied. They exhibited long‐lived blue phosphorescence in CHCl3 and a weak fluorescence in the UV. In MeOH/CHCl3 mixtures of >1:1 volume ratio, 1 and 2 exhibited a new emission band at ca. 540 nm that developed at the expense of the UV emission. DLS studies demonstrated the presence of molecular aggregates of Ø 30–80 nm. The green emission observed in MeOH‐rich solvent mixtures was therefore induced by aggregation, and could originate from Au⋅⋅⋅Au interactions. The AIE spectrum of 3 was observed only in solutions containing 99 % of MeOH, and correlated with its solid state emission. The AIE profiles of the enantiomers of 1 differed from that of rac‐1, suggesting that the latter is a true racemate. [ABSTRACT FROM AUTHOR]

During the synthesis of 1,10‐phenanthroline derivatives sterically hindered in the 2 and/or 9 positions, serendipity led to the discovery of a new substitution pattern on phenanthroline with good and reproducible yields. When toluene was used as a solvent and the aryl‐lithio reagents generated with tBuLi, after a first substitution at the 2 position, a benzyl substituent was regioselectively introduced at the 7 position. It is proposed that the benzyllithium reagent is formed by reaction with the solvent and that the steric hindrance on the intermediates controls the nucleophilic addition. Among the complexes prepared (Pd(II), Cu(I)) with these new ligands, a chiral copper(I) complex exhibits spontaneous resolution in the solid state. [ABSTRACT FROM AUTHOR]

Purpose: Currently, the most commonly used chelator for labelling antibodies with 89Zr for immunoPET is desferrioxamine B (DFO). However, preclinical studies have shown that the limited in vivo stability of the 89Zr-DFO complex results in release of 89Zr, which accumulates in mineral bone. Here we report a novel chelator DFOcyclo*, a preorganized extended DFO derivative that enables octacoordination of the 89Zr radiometal. The aim was to compare the in vitro and in vivo stability of [89Zr]Zr-DFOcyclo*, [89Zr]Zr-DFO* and [89Zr]Zr-DFO. Methods: The stability of 89Zr-labelled chelators alone and after conjugation to trastuzumab was evaluated in human plasma and PBS, and in the presence of excess EDTA or DFO. The immunoreactive fraction, IC50, and internalization rate of the conjugates were evaluated using HER2-expressing SKOV-3 cells. The in vivo distribution was investigated in mice with subcutaneous HER2+ SKOV-3 or HER2− MDA-MB-231 xenografts by PET/CT imaging and quantitative ex vivo tissue analyses 7 days after injection. Results: 89Zr-labelled DFO, DFO* and DFOcyclo* were stable in human plasma for up to 7 days. In competition with EDTA, DFO* and DFOcyclo* showed higher stability than DFO. In competition with excess DFO, DFOcyclo*-trastuzumab was significantly more stable than the corresponding DFO and DFO* conjugates (p < 0.001). Cell binding and internalization were similar for the three conjugates. In in vivo studies, HER2+ SKOV-3 tumour-bearing mice showed significantly lower bone uptake (p < 0.001) 168 h after injection with [89Zr]Zr-DFOcyclo*-trastuzumab (femur 1.5 ± 0.3%ID/g, knee 2.1 ± 0.4%ID/g) or [89Zr]Zr-DFO*-trastuzumab (femur 2.0 ± 0.3%ID/g, knee 2.68 ± 0.4%ID/g) than after injection with [89Zr]Zr-DFO-trastuzumab (femur 4.5 ± 0.6%ID/g, knee 7.8 ± 0.6%ID/g). Blood levels, tumour uptake and uptake in other organs were not significantly different at 168 h after injection. HER2− MDA-MB-231 tumour-bearing mice showed significantly lower tumour uptake (p < 0.001) after injection with [89Zr]Zr-DFOcyclo*-trastuzumab (16.2 ± 10.1%ID/g) and [89Zr]Zr-DFO-trastuzumab (19.6 ± 3.2%ID/g) than HER2+ SKOV-3 tumour-bearing mice (72.1 ± 14.6%ID/g and 93.1 ± 20.9%ID/g, respectively), while bone uptake was similar. Conclusion: 89Zr-labelled DFOcyclo* and DFOcyclo*-trastuzumab showed higher in vitro and in vivo stability than the current commonly used 89Zr-DFO-trastuzumab. DFOcyclo* is a promising candidate to become the new clinically used standard chelator for 89Zr immunoPET. [ABSTRACT FROM AUTHOR]

Cyclotricyanobenzylene (CTB) 1 was resolved by HPLC on chiral stationary phase and the absolute configurations of its enantiomers were determined. Optically‐active pallado‐ and platinocryptophanes assembled separately from (+)‐1 and (–)‐1, and the optical properties of [M3(dppp)3((+)‐1)2](OTf)6 and [M3(dppp)3((–)‐1)2](OTf)6 (M = Pd and Pt; dppp = 1,3‐bis(diphenylphosphanyl)propane) were studied by polarimetry and electronic circular dichroism (ECD). The enantiomerization barriers of the metallocryptophanes depend only weakly on the nature of the metal. TD‐DFT calculations demonstrated the occurence of induced ECD effects from the optically active CTB 1 to the metal complex fragments. Comparison of the 1H NMR spectra of the optically‐pure and racemic metallocryptophanes confirmed that the latter formed diastereoselectively and enantioselectively. Self‐assembly of metallocryptophanes from two different CTBs (1 and 2) gave clear evidence of chemoselectivity for the process, using 1H NMR spectroscopy and ESI‐MS. [ABSTRACT FROM AUTHOR]

This study compares the binding properties towards the uranyl cation of three hydroxamates derived from benzohydroxamic acid (BHAH), N-methylacetohydroxamic acid (NMAH) and 1-hydroxypiperidine-2-one (PIPOH), as models of the binding sites found in natural chelators that could be involved in the mobilization of uranyl in the vicinity of abandoned mines. Solution speciation studies of the UO22+/BHAH system by affinity capillary electrophoresis allowed to estimate stability constants for both ML [log K110 = 7.4(1)] and ML2 [log K120 = 7.0(1)] species in aqueous media [0.1 M (H,Na)ClO4, 25 °C], which lie in-between those reported by us elsewhere for NMA− and PIPO−. By contrast, gas phase studies demonstrate that one of the U=O bonds can be activated in the NMA− and PIPO− complexes, whereas this is not the case for the BHA− complex. [ABSTRACT FROM AUTHOR]

Many siderophores incorporate as bidentate chelating subunits linear and more seldomly cyclic hydroxamate groups. In this work, a comparative study of the uranyl binding properties in aqueous solution of two monohydroxamic acids, the prototypical linear N-methylacetohydroxamic acid (NMAH) and the cyclic analog 1-hydroxypiperidine-2-one (PIPOH), has been carried out. The complex [UO2(PIPO)2(H2O)] crystallized from slightly acidic water solutions (pH ＜ 5), and its molecular structure was determined by X-ray diffraction. The uranyl speciation in the presence of both ligands has been thoroughly investigated in a 0.1 M KNO3 medium at 298.2 K by the combined use of four complementary techniques, i.e., potentiometry, spectrophotometry, Raman spectroscopy, and affinity capillary electrophoresis. Preorganization of the hydroxamate ligand for chelation by incorporation into a cyclic structure, as in PIPO−, results in an increase of nearly one order of magnitude in the formation constants of the uranyl complexes of 1 : 1 and 1 : 2 metal/ligand stoichiometries. [ABSTRACT FROM AUTHOR]

Cryptophanes are receptors consisting of two bridging concave cyclotribenzylene (CTB) subunits. The formation of cryptophanes in basic aqueous solutions (0.1 m MOD; M = Li, Na, K, and Cs) by disulfide bridge formation has been investigated. Two original CTBs, 1H6 and 2H6, derived from cyclotriphenolene through the introduction of mercaptomethyl and mercapto substituents, respectively, were synthesized. Cryptophane formation by slow oxygenation of 16- was observed only in the presence of Me4N+ as template, which yielded the diastereomeric forms in a ratio of around 82:18. By contrast, the rigid CTB 2H6 yielded a cryptophane stereoselectively without a template. Interestingly, air oxidation of a 1:1 mixture of 16- and 26- in the presence of Me4N+ (0.5-1 equiv./ 16-) in 0.1 m LiOD led to the exclusive formation of the cryptophane complex [( 1·1)6-⊃+NMe4], ( 2·2)6- being formed only in very minor amounts. No mixed species were detected in the reaction mixtures. The stabilities of the diastereomers of the protonated cryptophanes were calculated in the gas phase by DFT at the ωB97XD 6-311G(d,p) level of theory. [ABSTRACT FROM AUTHOR]

Cryptophanes are macropolycyclic cyclophanes constructed from two triply bridged concave cyclotriveratrylene analogues that encapsulate a large range of molecular and monoatomic substrates. Self-assembled metallo-organic cryptophanes based on M2+-carbonitrile (M = Pd or Pt) interactions have been obtained through the reactions of chiral nitrile-substituted cyclotribenzylenes (CTBs) 1 and 2 with [M(dppp)][OTf]2 (dppp = 1,3-bisdiphenylphosphinopropane, OTf = triflate) in 2:3 ratios in chlorinated solvents. The cryptophanes [Pd3(dppp)3( 1)2]6+ and [Pd3(dppp)3( 2)2]6+ were obtained exclusively in the chiral anti form in solution at room temperature whatever solvent was used; however the meso, syn form was identified as the major isomer of [Pd3(dppp)3( 1)2]6+ at low temperature in CD2Cl2, and - in the case of [Pt3(dppp)3( 1)2]6+ - it formed in a minor amount at room temperature. [Pd3(dppp)3( 1)2][OTf]6 and [Pt3(dppp)3( 1)2][OTf]6 crystallized in the anti forms with an encapsulated chloroform molecule, and gas-phase DFT calculations with the dispersion-corrected B97-D3 functional show that it is stabilized by 34.6 kJ mol-1. Interestingly, the heteroleptic cryptophane [Pd3(dppp)3( 1)( 2)]6+ was not detected in mixtures of [Pd(dppp)]2+ and CTBs 1 and 2 in a 3:1:1 ratio or through the equilibration of a 1:1 mixture of the preformed homoleptic cryptophanes; this points to favored self-sorting processes. [ABSTRACT FROM AUTHOR]

Six- and seven-membered cyclic hydroxamic acids, such as 1-hydroxypiperidine-2-one ( 1H, 1,2-PIPOH) and 1-hydroxyazepan-2-one ( 2H), have recently been identified in some mixed siderophores as one of their three chelating subunits. Compared to their ubiquitous noncyclic counterparts, cyclic hydroxamates are preorganized for metal binding. Surprisingly, the coordination chemistry of these bidentate, monoanionic ligands remains virtually unknown, even in the case of iron(III). We report herein the first structural study of the complexes of 1- and of 6-, an unsaturated seven-membered ring analog of 2-, with tetravalent cations of transition metals (zirconium and hafnium), lanthanide (cerium), and actinides (thorium and uranium). Structural characterization by means of X-ray crystallography of the corresponding ML4 complexes evidenced distorted square antiprismatic coordination geometries with the exception of U4+, which favors a dodecahedral arrangement. [ABSTRACT FROM AUTHOR]

Disulfide-bond formation is an expeditious coupling reaction to make macropolycyclic symmetrical receptors. It is used here for the preparation of unsymmetrical cavitands based on α-cyclodextrin (α-CDX) and cyclotriveratrylene (CTV) analogues. Accordingly, diastereomeric hemicryptophanes 2a and 2b were obtained in 11 % isolated yield by the iodine oxidation of a 1:1 mixture of racemic cyclotrithiophenolene ( 3) and the C3-symmetric trithiol derivative of permethylated α-cyclodextrin (PM α-CDX) 4. Remarkably, the target hemicryptophanes were obtained in a 5:3 diastereomeric ratio. The reaction produced mainly (34 %) a singly disulfide-bridged PM α-CDX dimer 7, however no traces of triply disulfide-bridged head-to-head PM α-CDX dimer were detected. In addition, the formation of the known S-cryptophane-0.0.0 was observed. [ABSTRACT FROM AUTHOR]

Topological constructions made from closed curves range from simple links to intricate knots and started to capture the chemists' attention in the early sixties. These mathematical objects result from particular embeddings of a single or a set of closed curves in the three-dimensional space that show an infinite variety of presentations. Simple catenanes, higher order interlocked macrocycles, and molecular knots can be synthesized via the metal template approach, just as simple macrocycles. However, this requires that rigid presentations with appropriate geometrical characteristics be identified prior to molecular design, and those selected for the metal-templated synthesis of some of these fascinating molecules are reviewed here. [ABSTRACT FROM AUTHOR]

In DFO*, the trihydroxamate DFO is elongated with an extra hydroxamate group, exactly the same as present in DFO. Initially the in vivo stability of [ SP 89 sp Zr]Zr-DFOcyclo*-trastuzumab was compared with [ SP 89 sp Zr]Zr-DFO-trastuzumab, of which the results are depicted in Fig. [Extracted from the article]

Cover Feature: A New Phenanthroline Ligand and the Spontaneous Resolution of its Homoleptic Copper(I) Complex (Eur. J. Org. B The Cover Feature b shows a new substitution pattern obtained when reacting phenanthrolines with organolithium compounds. More information can be found in the Full Paper by R. Ruppert et al. GLO:5AG/20dec20:ejoc202001375-toc-0001.jpg PHOTO (COLOR): . gl B The Cover Feature b shows a new substitution pattern obtained when reacting phenanthrolines with organolithium compounds. [Extracted from the article]