Bone health and skeletal fragility in second- and third-line medical therapies for acromegaly: preliminary results from a pilot single center experience.

INTRODUCTION: Skeletal fragility is a clinically relevant and not-reversible complication of acromegaly, involving around 30-40% of patients since the disease diagnosis. Few studies have investigated the effects on skeletal health of medical therapies for acromegaly. In this retrospective longitudinal monocentre study, we investigated the outcome of skeletal fragility in patients treated with Pasireotide Lar in combination with Pegvisomant (Pasi-Lar + Peg-V), also comparing those observed in patients treated with conventional therapies. RESULTS: We included 6 patients treated with Pasi-Lar + Peg-V, 5 patients treated with Peg-V in monotherapy (m-Peg-V), 16 patients treated with Peg-V plus first-generation somatostatin receptor ligands (fg-SRLs + Peg-V), 9 patients treated with Pasi-Lar. None of the patients treated with Pasi-Lar + Peg-V experienced worsening of spine and femoral bone mineral density (BMD) and incident vertebral fractures (i-VFs). Eight patients experienced i-VFs. The frequency of i-VFs was significantly lower in patients treated with the Pasi-Lar + Peg-V (0/8; 0%), as compared to those observed in m-Peg-V treated patients (4/8; 50%, p = 0.02). The frequency of i-VFs was slightly but not significantly higher in Pasi-Lar treated patients (1/8; 12.5% p = 0.6) and in fg-SRLs + Peg-V treated patients (3/8; 37.5% p = 0.364), concerning those treated with Pasi-Lar + Peg-V (0/8; 0%). I-VFs occurred more frequently in patients with higher GH levels at acromegaly diagnosis (p < 0.001), and in patients who experienced a BMD worsening (p = 0.005). CONCLUSION: Our preliminary data suggested that in conventional and multi-drug resistant acromegaly, the combination therapy Pasi-Lar + Peg-V may prevent the worsening of BMD and the occurrence of i-VFs. Prospective and translational studies should further validate these results and ascertain underlying physiopathology mechanisms.

Pediatric craniopharyngiomas: magnetic resonance imaging assessment for hypothalamus-pituitary axis dysfunction and outcome prediction.

BACKGROUND: In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis. OBJECTIVE: To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas. MATERIALS AND METHODS: We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2min). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes. RESULTS: Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), and between peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34). CONCLUSION: Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2min intensity of the tumor cystic component are independent predictors of extent of adamantinomatous craniopharyngioma excision and recurrence.

The Pathogenic RET Val804Met Variant in Acromegaly: A New Clinical Phenotype?

Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report the first acromegaly patient carrying a RET pathogenic variant: c.2410G>A (rs79658334), p.Val804Met. Alongside the fact that the patient's father and daughter carried the same variant, we investigated the clinical significance of this variant in the context of somatotropinomas and other endocrine tumors, reviewing the RET mutations' oncogenic mechanisms. The aim was to search for new targets to precisely manage and treat acromegaly. Our case describes a new phenotype associated with the RET pathogenic variant, represented by aggressive acromegaly, and suggests consideration for RET mutation screening if NGS for well-established PitNET-associated gene mutations renders negative.

Chemical Tailoring of ß-Cyclodextrin-Graphene Oxide for Enhanced Per- and Polyfluoroalkyl Substances (PFAS) Adsorption from Drinking Water.

We report on the synthesis of ß-cyclodextrin (ßCD) modified graphene oxide (GO) nanosheets, having different sized alkyl linkers (GO-Cn -ßCD) and their exploitation as sorbent of per- and polyfluoroalkyl substances (PFAS) from drinking water. ßCD were functionalized with a pending amino group, and the resulting precursors grafted to GO nanosheets by epoxide ring opening reaction. Loading of ßCD units in the range 12 %-36 % was estimated by combined XPS and elemental analysis. Adsorption tests on perfluorobutanoic acid (PFBA), a particularly persistent PFAS selected as case study, revealed a strong influence of the alkyl linker length on the adsorption efficiency, with the hexyl linker derivative GO-C6 -ßCD outperforming both pristine GO and granular activated carbon (GAC), the standard sorbent benchmark. Molecular dynamic simulations ascribed this evidence to the favorable orientation of the ßCD unit on the surface of GO which enables a strong contaminant molecules retention.

Safety and efficacy of endoscopic ultrasound-guided radiofrequency ablation for pancreatic insulinoma: A single-center experience.

BACKGROUND/OBJECTIVES: Insulinomas are rare, functioning pancreatic neuroendocrine neoplasms (pNEN), whose gold standard therapy is surgical resection. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a recent technique that has emerged as a minimally invasive therapeutic option for patients with pancreatic lesions not eligible for surgery. In this study, we aimed to describe a series of patients with unresectable pancreatic insulinoma treated with EUS-RFA. METHODS: This is a single-center, retrospective study including all consecutive patients with functioning pancreatic insulinoma undergoing EUS-RFA for surgical unfitness or surgery refusal, between March 2017 and September 2021. Technical success (i.e., complete mass ablation), adverse event rate and severity, clinical and radiologic outcomes (i.e., symptom remission with a normal concentration of blood glucose, and the presence of intralesional necrosis), and post-procedural follow-up were assessed. RESULTS: A total of 10 patients (mean age: 67.1 ± 10.1years; F:M 7:3) were included. The mean size of insulinoma was 11.9 ± 3.3 mm. Technical success and clinical remission were achieved in 100% of patients. Only one (10%) patient was successfully treated with two RFA sessions. Two procedure-related early adverse events occurred, including two (20%) cases of mild abdominal pain. No major complications were observed. The complete radiologic response within 3 months after EUS-RFA was observed in all patients (100%). After a median follow-up of 19.5 (range12-59) months, symptom remission and persistent euglycemia were assessed in all the patients. CONCLUSIONS: Data from this case series suggest that EUS-RFA is a feasible and safe therapeutic approach for pancreatic insulinomas in patients unwilling or unable to undergo surgery with medium-term efficacy.

Selective recognition of neurotransmitters in aqueous solution by hydroxyphenyl aza-scorpiand ligands.

The synthesis, acid-base behaviour and anion recognition of neurotransmitters (dopamine, tyramine and serotonin) in aqueous solution of different aza-scorpiand ligands functionalized with hydroxyphenyl and phenyl moieties (L1-L3 and L4, respectively) have been studied by potentiometry, NMR, UV-Vis and fluorescence spectroscopy and isothermal titration calorimetry (ITC). The analysis of the potentiometric results shows the selective recognition of serotonin at physiological pH (Keff = 8.64 × 104) by L1. This selectivity has an entropic origin probably coming from a fine pre-organization of the interacting partners. Thus, the complementarity of the receptor and the substrate allows the reciprocal formation of hydrogen bonds, π-π and cation-π interactions, stabilizing the receptors and slowing the rate of oxidative degradation, and satisfactory results are obtained at acidic and neutral pH values. NMR and molecular dynamics studies reveal the rotation blockage in the neurotransmitter side chain once complexed with L1.

Aggressive PitNETs and Potential Target Therapies: A Systematic Review of Molecular and Genetic Pathways.

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.

A Norbornadiene-Based Molecular System for the Storage of Solar-Thermal Energy in an Aqueous Solution: Study of the Heat-Release Process Triggered by a Co(II)-Complex.

It is urgent yet challenging to develop new environmentally friendly and cost-effective sources of energy. Molecular solar thermal (MOST) systems for energy capture and storage are a promising option. With this in mind, we have prepared a new water-soluble (pH > 6) norbornadiene derivative (HNBD1) whose MOST properties are reported here. HNBD1 shows a better matching to the solar spectrum compared to unmodified norbornadiene, with an onset absorbance of λonset = 364 nm. The corresponding quadricyclane photoisomer (HQC1) is quantitatively generated through the light irradiation of HNBD1. In an alkaline aqueous solution, the MOST system consists of the NBD1-/QC1- pair of deprotonated species. QC1- is very stable toward thermal back-conversion to NBD1-; it is absolutely stable at 298 K for three months and shows a marked resistance to temperature increase (half-life t½ = 587 h at 371 K). Yet, it rapidly (t½ = 11 min) releases the stored energy in the presence of the Co(II) porphyrin catalyst Co-TPPC (ΔHstorage = 65(2) kJ∙mol-1). Under the explored conditions, Co-TPPC maintains its catalytic activity for at least 200 turnovers. These results are very promising for the creation of MOST systems that work in water, a very interesting solvent for environmental sustainability, and offer a strong incentive to continue research towards this goal.

Assembly of Polyiodide Networks with Cu(II) Complexes of Pyridinol-Based Tetraaza Macrocycles.

Polyiodide networks are currently of great practical interest for the preparation of new electronic materials. The participation of metals in the formation of these networks is believed to improve their mechanical performance and thermal stability. Here we report the results on the construction of polyiodide networks obtained using Cu(II) complexes of a series of pyridinol-based tetraazacyclophanes as countercations. The assembly of these crystalline polyiodides takes place from aqueous solutions on the basis of similar structural elements, the [CuL]2+ and [Cu(H-1L)]+ (L = L2, L2-Me, L2-Me3) complex cations, so that the peculiarities induced by the increase of N-methylation of ligands, the structural variable of ligands, can be highlighted. First, solution equilibria involving ligands and complexes were analyzed (potentiometry, NMR, UV-vis, ITC). Then, the appropriate conditions could be selected to prepare polyiodides based on the above complex cations. Single-crystal XRD analysis showed that the coordination of pyridinol units to two metal ions is a prime feature of these ligands, leading to polymeric coordination chains of general formula {[Cu(H-1L)]}nn+ (L = L2-Me, L2-Me3). In the presence of the I-/I2 couple, the polymerization tendency stops with the formation of [(CuL)(CuH-1L)]3+ (L = L2-Me, L2-Me3) dimers which are surrounded by polyiodide networks. Moreover, coordination of the pyridinol group to two metal ions transforms the surface charge of the ring from negative to markedly positive, generating a suitable environment for the assembly of polyiodide anions, while N-methylation shifts the directional control of the assembly from H-bonds to I···I interactions. In fact, an extended concatenation of iodine atoms occurs around the complex dimeric cations, the supramolecular I···I interactions become shorter and shorter, fading into stronger forces dominated by the orbital overlap, which is promising for effective electronic materials.

Noncovalent Assembly and Catalytic Activity of Hybrid Materials Based on Pd Complexes Adsorbed on Multiwalled Carbon Nanotubes, Graphene, and Graphene Nanoplatelets.

Green catalysts with excellent performance in Cu-free Sonogashira coupling reactions can be prepared by the supramolecular decoration of graphene surfaces with Pd(II) complexes. Here we report the synthesis, characterization, and catalytic properties of new catalysts obtained by the surface decoration of multiwalled carbon nanotubes (MWCNTs), graphene (G), and graphene nanoplatelets (GNPTs) with Pd(II) complexes of tetraaza-macrocyclic ligands bearing one or two anchor functionalities. The decoration of these carbon surfaces takes place under environmentally friendly conditions (water, room temperature, aerobic) in two steps: (i) π-π stacking attachment of the ligand via electron-poor anchor group 6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxo-pyrimidine and (ii) Pd(II) coordination from PdCl42-. Ligands are more efficiently adsorbed on the flat surfaces of G and GNPTs than on the curved surfaces of MWCNTs. All catalysts work very efficiently under mild conditions (50 °C, aerobic, 7 h), giving a similar high yield (90% or greater) in the coupling of iodobenzene with phenylacetylene to form diphenylacetylene in one catalytic cycle, but catalysts based on G and GNPTs (especially on GNPTs) provide greater catalytic efficiency in reuse (four cycles). The study also revealed that the active centers of the ligand-Pd type decorating the support surfaces are much more efficient than the Pd(0) and PdCl42- centers sharing the same surfaces. All of the results allow a better understanding of the structural factors to be controlled in order to obtain an optimal efficiency from similar catalysts based on graphene supports.

Impact of the diagnostic delay of acromegaly on bone health: data from a real life and long term follow-up experience.

INTRODUCTION: Acromegaly is a chronic disease with systemic complications. Disease onset is insidious and consequently typically burdened by diagnostic delay. A longer diagnostic delay induces more frequently cardiovascular, respiratory, metabolic, neuropsychiatric and musculoskeletal comorbidities. No data are available on the effect of diagnostic delay on skeletal fragility. We aimed to evaluate the effect of diagnostic delay on the frequency of incident and prevalent of vertebral fractures (i-VFs and p-VFs) in a large cohort of acromegaly patients. PATIENTS AND METHODS: A longitudinal, retrospective and multicenter study was conducted on 172 acromegaly patients. RESULTS: Median diagnostic delay and duration of follow-up were respectively 10 years (IQR: 6) and 10 years (IQR: 8). P-VFs were observed in 18.6% and i-VFs occurred in 34.3% of patients. The median estimated diagnostic delay was longer in patients with i-VFs (median: 11 years, IQR: 3), in comparison to those without i-VFs (median: 8 years, IQR: 7; p = 0.02). Age at acromegaly diagnosis and at last follow-up were higher in patients with i-VFs, with respect to those without i-VFs. The age at acromegaly diagnosis was positively associated with the diagnostic delay (p < 0.001, r = 0.216). A longer history of active acromegaly was associated with a high frequency of i-VFs (p = 0.03). The logistic regression confirmed that patients with a diagnostic delay > 10 years had 1.5-folds increased risk of developing i-VFs (OR: 1.5; 95%CI: 1.1-2; p = 0.017). CONCLUSION: Our data showed that the diagnostic delay in acromegaly has a significant impact on VF risk, further supporting the clinical relevance of an early acromegaly diagnosis.

Core-shell graphene oxide-polymer hollow fibers as water filters with enhanced performance and selectivity.

Commercial hollow fiber filters for micro- and ultrafiltration are based on size exclusion and do not allow the removal of small molecules such as antibiotics. Here, we demonstrate that a graphene oxide (GO) layer can be firmly immobilized either inside or outside polyethersulfone-polyvinylpyrrolidone hollow fiber (Versatile PES®, hereafter PES) modules and that the resulting core-shell fibers inherits the microfiltration ability of the pristine PES fibers and the adsorption selectivity of GO. GO nanosheets were deposited on the fiber surface by filtration of a GO suspension through a PES cartridge (cut-off 0.1-0.2 µm), then fixed by thermal annealing at 80 °C, rendering the GO coating stably fixed and unsoluble. The filtration cut-off, retention selectivity and efficiency of the resulting inner and outer modified hollow fibers (HF-GO) were tested by performing filtration on water and bovine plasma spiked with bovine serum albumin (BSA, 66 kDa, ≈15 nm size), monodisperse polystyrene nanoparticles (52 nm and 303 nm sizes), with two quinolonic antibiotics (ciprofloxacin and ofloxacin) and rhodamine B (RhB). These tests showed that the microfiltration capability of PES was retained by HF-GO, and in addition the GO coating can capture the molecular contaminants while letting through BSA and smaller polystyrene nanoparticles. Combined XRD, molecular modelling and adsorption experiments show that the separation mechanism does not rely only on physical size exclusion, but involves intercalation of solute molecules between the GO layers.

Multidimensional geriatric evaluation in acromegaly: a comparative cross-sectional study.

BACKGROUND: Improvement in acromegaly management increased disease survival and prevalence. Evidence regarding acromegaly in older adults are sparse. We aim to explore acromegaly impact on aging process quality. METHODS: Multicenter case-control study conducted on 42 older adults (≥ 65 years) acromegaly patients (ACRO) compared to an age- and gender-matched control group (CTR). Each participant underwent a multidimensional geriatric evaluation. RESULTS: Mean age in both groups was 73 ± 6 years and female gender was most represented (69%). All comorbidities were more frequent in ACRO than CTR. Thirteen ACRO were in remission and 29 had active disease controlled by medical therapy except for one patient. ACRO showed worse physical performance and mobility skills worsening with age as compared to CTR. ACRO performed poorly in functional status assessment, and age negatively correlated with instrumental and basic daily activities execution. Cognitive evaluation scores were significantly lower in ACRO vs. CTR, worsening with age. No difference was found concerning nutritional and psychological status. Musculoskeletal and bone diseases were more frequent in ACRO than in CTR (52% vs. 12%; 64% vs. 10%; P < 0.05) and independently associated with geriatric outcomes in ACRO. ACRO reported a less satisfactory quality of life concerning physical activity and pain, general health, vitality, social activities. CONCLUSIONS: Our study demonstrates increased frailty of older acromegaly patients as compared to non-acromegaly patients with a consequent negative impact on their quality of life. Therefore, it seems advisable to include physical, functional, cognitive, nutritional, and psychological status assessments in routine clinical practice. Further studies are needed to identify the most appropriate geriatric tools.

Metal Coordination Properties of a Chromophoric Desferrioxamine (DFO) Derivative: Insight on the Coordination Stoichiometry and Thermodynamic Stability of Zr4+ Complexes.

Desferrioxamine (DFO) is the current "gold standard" chelator for 89Zr4+, which is used to label monoclonal antibodies for applications in immunopositron emission tomography. Recently, controversial data have been reported regarding the speciation and the stability of the complexes formed by DFO with Zr4+ in solution. To shed some light on this point, we studied the coordination properties in solution ofa chromophoric DFO derivative bearing a substituted pyrimidine residue (DFO-Pm) toward several metal ions (Zr4+, Cu2+, Zn2+, Mg2+, Ca2+, Na+, K+). Potentiometric titrations showed that DFO-Pm and pristine DFO form complexes with very similar stoichiometry and stability. DFO-Pm, which can consequently be taken as a model system for DFO, provides a photochemical response to metal coordination that can be used to further define the complexes formed. In the critical case of Zr4+, spectrophotometric measurements allowed the verification of the formation of 1:1 and 2:3 complexes that, together with 2:2 complexes form the coordination model that was obtained through the use of our potentiometric measurements. Additionally, mass spectrometry measurements verified the formation of 1:1 and 2:3 complexes and showed that 1:2 species can be easily generated through the fragmentation of the 2:3 species. In conclusion, the results obtained with DFO-Pm validate the complexation model of Zr4+/DFO composed of 1:1, 2:2, and 2:3 metal-to-ligand complexes. Convergences and conflicts with other works are addressed.

Porous Frameworks Based on Supramolecular Ball Joints: Bringing Flexibility to Ordered 3D Lattices.

XOFs-type materials (X=M, C, S, that is, metal-organic frameworks, covalent organic frameworks and supramolecular organic frameworks, respectively) share a common unifying feature: mutual spatial orientation of constituting components is strictly directional and unchanging by design. Herein, we illustrate an alternate design for porous architectures, as rigid joints constituted by coordinative (MOFs), covalent (COFs), or hydrogen-donor/acceptor (SOFs) bonds, are replaced by supramolecular ball joints, which confer unprecedented flexibility, especially angular, to porous networks. The obtained frameworks remain highly organized but are also permutable: lacking a forced convergence towards an immutable minimum energy structure, these systems remain able to adjust depending on external conditions. Results of POF (permutable organized framework) synthesis is a family of structures rather than a single pre-determined three-dimensional arrangement, as we demonstrate with an illustrative set of 5 XRD structures.

SPONTANEOUS THYROID NODULE HEMORRHAGE IN THE EMERGENCY DEPARTMENT.

Objective: Spontaneous thyroid gland hemorrhage is a rare event. The present retrospective study considered its clinical impact and management in a referral center. Methods: Clinical records of adult patients accessed in the last 10 years (2009-2018) in the Emergency Department of Policlinico Gemelli IRCCS were reviewed to study patients with spontaneous thyroid nodule hemorrhage. All demographic and radiologic or surgical parameters were included, with special attention to the characteristics of thyroid disease and clinical management. Results: Among the 631,129 adults who were registered during the period considered, 59 consecutive patients were included in the study. The mean age was 48.3 ± 14.3 years, with a prevalence of females. The main symptoms were acute neck pain, dyspnea, and dysphagia. All patients underwent ultrasound evaluation; computed tomography scan was performed on only 3 patients, finding one case of active intranodular bleeding requiring urgent surgery. Six patients required hospitalization; the others were discharged and referred for ambulatory endocrinology follow-up. Among them, 7 patients underwent surgery in the next 6 months, with malignant disease found in 3 cases (5.1%). Conclusion: Intrathyroidal spontaneous hemorrhage is a rare event, occurring in multinodular as well as in single-nodule thyroid disease. Although the clinical course is mostly benign, this condition should be carefully evaluated as, in rare circumstances, active bleeding could induce airway obstruction with the need for emergency surgery. Patients should be referred to endocrinology ambulatory follow-up because bleeding could arise as the first sign of malignant lesions in some cases. Abbreviations: CT = computed tomography; ED = emergency department; FNA = fine-needle aspiration; US = ultrasound.

Stabilisation of Exotic Tribromide (Br3-) Anions via Supramolecular Interaction with A Tosylated Macrocyclic Pyridinophane. A Serendipitous Case.

Tetraaza-macrocyclic pyridinophane L-Ts, decorated with a p-toluenesulfonyl (tosyl; Ts) group, appear to be a useful tool to provide evidence on how the interplay of various supramolecular forces can help stabilise exotic anionic species such as tribromide (Br3-) anions. Indeed, crystals of (H2L-Ts)(Br3)1.5(NO3)0.5 unexpectedly grew from an acidic (HNO3) aqueous solution of L-Ts in the presence of Br- anions. The crystal structure of this compound was determined by single crystal XRD analysis. Hydrogen bonds, salt-bridges, anion-, - stacking, and van der Waals interactions contribute to stabilising the crystal lattice. The observation of two independent Br3- anions stuck over the π-electron densities of pyridine and tosyl ligand groups, one of them being sandwiched between two pyridine rings, corroborates the significance of anion-π interactions for N-containing heterocycles. We show herein the possibility of detecting anion-π contacts from fingerprint plots generated by Hirshfeld surface analysis, demonstrating the effective usage of this structural investigation technique to further dissect individual contributions of stabilising supramolecular forces.

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.

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.

Solid State and Solution Study on the Formation of Inorganic Anion Complexes with a Series of Tetrazine-Based Ligands.

Four molecules (L1-L4) constituted by an s-tetrazine ring appended with two identical aliphatic chains of increasing length bearing terminal morpholine groups were studied as anion receptors in water. The basicity properties of these molecules were also investigated. Speciation of the anion complexes formed in solution and determination of their stability constants were performed by means of potentiometric (pH-metric) titrations, while further information was obtained by NMR and isothermal titration calorimetry (ITC) measurements. The crystal structures of two neutral ligands (L3, L4) and of their H2L3(ClO4)2∙2H2O, H2L4(ClO4)2∙2H2O, H2L3(PF6)2, and H2L3(PF6)2∙2H2O anion complexes were determined by single crystal X-ray diffraction. The formation of anion-π interactions is the leitmotiv of these complexes, both in solution and in the solid state, although hydrogen bonding and/or formation of salt-bridges can contribute to their stability. Evidence of the ability of these ligands to form anion-π interactions is given by the observation that even the neutral (not-protonated) molecules bind anions in water to form complexes of significant stability, including elusive OH- anions.