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

Novel insights on saccharin- and acesulfame-based carbonic anhydrase inhibitors: design, synthesis, modelling investigations and biological activity evaluation

A large library of saccharin and acesulfame derivatives has been synthesised and evaluated against four isoforms of human carbonic anhydrase, the two off-targets hCA I/II and the tumour related isoforms hCA IX/XII. Different strategies of scaffold modification have been attempted on both saccharin as well as acesulfame core leading to the obtainment of 60 compounds. Some of them exhibited inhibitory activity in the nanomolar range, albeit some of the performed changes led to either micromolar activity or to its absence, against hCA IX/XII. Molecular modelling studies focused the attention on the binding mode of these compounds to the enzyme. The proposed inhibition mechanism is the anchoring to zinc-bound water molecule. Docking studies along with molecular dynamics also underlined the importance of the compounds flexibility (e.g. achieved through the insertion of methylene group) which favoured potent and selective hCA inhibition

4-Hydroxy-3-nitro-5-ureido-benzenesulfonamides selectively target the tumor-associated carbonic anhydrase isoforms IX and XII showing hypoxia-enhanced anti-proliferative profiles.

Human carbonic anhydrases (CA, EC, 4.2.1.1) IX and XII are overexpressed in cancer cells as adaptive response to hypoxia and acidic conditions characteristic of many tumors. In addition, hypoxia facilitates the activity of specific oxido-reductases that may be exploited to selectively activate bioreductive prodrugs. Here, new selective CA IX/XII inhibitors, as analogues of the antitumor phase II drug SLC-0111 are described, namely ureido-substituted benzenesulfonamides appended with a nitro-aromatic moiety to yield an antiproliferative action increased by hypoxia. These compounds were screened for the inhibition of the ubiquitous hCA I/II and the target hCA IX/XII. Six X-ray crystallographies with CA II and IX/mimic allowed for the rationalization of the compounds inhibitory activity. The effects of some such compounds on the viability of HT-29, MDA-MB-231, and PC-3 human cancer cell lines in both normoxic and hypoxic conditions were examined, providing the initiation toward the development of hypoxia-activated antitumor CAIs

Induction of a Four‐Way Junction Structure in the DNA Palindromic Hexanucleotide 5′‐d(CGTACG)‐3′ by a Mononuclear Platinum Complex

Four‐way junctions (4WJs) are supramolecular DNA assemblies comprising four interacting DNA strands that in biology are involved in DNA‐damage repair. In this study, a new mononuclear platinum(II) complex 1 was prepared that is capable of driving the crystallization of the DNA oligomer 5′‐d(CGTACG)‐3′ specifically into a 4WJ‐like motif. In the crystal structure of the 1–CGTACG adduct, the distorted‐square‐planar platinum complex binds to the core of the 4WJ‐like motif through π–π stacking and hydrogen bonding, without forming any platinum–nitrogen coordination bonds. Our observations suggest that the specific molecular properties of the metal complex are crucially responsible for triggering the selective assembly of this peculiar DNA superstructure.Metals in Catalysis, Biomimetics & Inorganic Material

Induction of a four-way junction structure in the DNA palindromic hexanucleotide 5 '-d(CGTACG)-3 ' by a mononuclear platinum complex

Four-way junctions (4WJs) are supramolecular DNA assemblies comprising four interacting DNA strands that in biology are involved in DNA-damage repair. In this study, a new mononuclear platinum(II) complex 1 was prepared that is capable of driving the crystallization of the DNA oligomer 5 '-d(CGTACG)-3 ' specifically into a 4WJ-like motif. In the crystal structure of the 1-CGTACG adduct, the distorted-square-planar platinum complex binds to the core of the 4WJ-like motif through pi-pi stacking and hydrogen bonding, without forming any platinum-nitrogen coordination bonds. Our observations suggest that the specific molecular properties of the metal complex are crucially responsible for triggering the selective assembly of this peculiar DNA superstructure.Metals in Catalysis, Biomimetics & Inorganic Material

The evolution of the Australian ‘ndrangheta. An historical perspective

This paper explores the phenomenon of the ‘ndrangheta – a criminal organisation from Calabria, South of Italy and allegedly the most powerful among the Italian mafias – through its migrating routes. In particular, by focusing on the peculiar case of Australia, the paper aims to show the overlapping of migrating flows with criminal colonisation, which has proven to be a strategy of this particular mafia. The paper uses the very thin literature on the subject alongside official reports and newspaper articles on migration and crime, mainly from Italian sources, to trace an historical journey on the migration of people from Calabria to Australia in various moments of the last century. The aim is to present the evolution and growth of Calabrian clans in Australia. The topic is largely unexplored and is still underreported among Australian institutions and scholars, which is why the paper chooses an historical approach to describe the principal paths in this very new field of research