Chiara Massera

Structure, Cytotoxicity, and DNA-Cleavage Properties of the Complex [CuII(pbt)Br2]

The reactions of the ligand 2-(2-pyridyl)benzthiazole (pbt) with CuBr 2 and ZnCl 2 in acetonitrile produce the complexes [Cu(pbt)Br 2] ( 1) and [Zn(pbt)Cl 2] ( 3), respectively. When complex 1 is dissolved in DMF, complex 2 is obtained as light-green crystals. The reaction of pbt with CuBr 2 in DMF also yields the complex [Cu(pbt)Br 2(dmf)] ( 2) (dmf = dimethylformamide). Complexes 1- 3 were characterized by X-ray crystallography. Complexes 1 and 3 have distorted tetrahedral coordination environments, and complex 2 is constituted of two slightly different copper centers, both exhibiting distorted trigonal bipyramidal geometries. Complexes 1 and 2 cleave phiX174 phage DNA, both in the presence and the absence of reductant. The free ligand pbt does not show any DNA-cleaving abilities. The poor solubility of complex 3 makes it not applicable for biological tests. The occurrence of DNA breaks in the presence of various radical scavengers suggests that no diffusible radicals are involved in the DNA cleavage by complex 1, as none of the scavengers inhibit the cleavage reaction. The DNA-cleavage products are not religated with the enzyme T4 DNA ligase, which is an additional proof that the cleavage is nonhydrolytic. Most probably the cleaving reaction involves reactive oxygen species, which could not be trapped, leading to an oxidative mechanism. An easy oxidation of Cu (II)(pbt)Br 2 to Cu (III) in DMF and the reduction of the same to Cu (I), under similar electrochemical conditions may lead to the in situ activation of molecular oxygen, resulting in the formation of metal solvated nondiffusible radicals able to prompt the oxidative cleavage of DNA. Complex 1 and the pure ligand exhibit remarkable cytotoxic effects against the cancer cell lines L1210 and A2780 and also against the corresponding cisplatin-resistant mutants of these cell lines.

Supramolecular Sensing with Phosphonate Cavitands

Phosphonate cavitands are an emerging class of synthetic receptors for supramolecular sensing. The molecular recognition properties of the third-generation tetraphosphonate cavitands toward alcohols and water at the gas-solid interface have been evaluated by means of three complementary techniques and compared to those of the parent mono- and diphosphonate cavitands. The combined use of ESI-MS and X-ray crystallography defined precisely the host-guest association at the interface in terms of type, number, strength, and geometry of interactions. Quartz crystal microbalance (QCM) measurements then validated the predictive value of such information for sensing applications. The importance of energetically equivalent multiple interactions on sensor selectivity and sensitivity has been demonstrated by comparing the molecular recognition properties of tetraphosphonate cavitands with those of their mono- and diphosphonate counterparts.

Design and self-assembly of wide and robust coordination cages

The self-assembly of a new class of coordination cages formed from two tetrapyridyl-substituted cavitands connected through four square-planar palladium or platinum complexes is reported. The shape of the internal cavity resembles an ellipsoid with a calculated volume of 840 Å3. The four lateral portals have a diameter of about 6 Å, large enough to allow the fast entrance/egress of counterions in solution. The platinum cages 3a,e cannot be disassembled using triethylamine as competitive ligand and they are kinetically stable at room temperature, whereas the palladium cages 3b-d, 3f-h are disassembled and kinetically labile under the same conditions. The different solubility properties of the cage components have allowed the extension of this self-assembly protocol to the liquid–liquid interface.

Stereoselective Synthesis of (E)‐3‐(Methoxycarbonyl)methylene‐1,3‐dihydroindol‐2‐ones by Palladium‐Catalyzed Oxidative Carbonylation of 2‐Ethynylanilines

A direct synthesis of (E)-3-(methoxycarbonyl)methylene-1,3-dihydroindol-2-ones 2 by palladium-catalyzed oxidative carbonylation of 2-ethynylanilines 1 is reported. Reactions were carried out in MeOH as the solvent at 50−70 °C in the presence of catalytic amounts of PdI2 in conjunction with KI under a 4:1 CO/air mixture (20 atm total pressure at 25 °C). When the reaction was applied to 2-alkynylanilines with internal triple bonds, the reaction course changed completely, with formation of carbamates 4.

Exploration of CH⋯π interactions involving the π-system of pseudohalide coligands in metal complexes of a Schiff-base ligand

A series of four mononuclear Schiff-base complexes, namely, [Zn(L)(NCS)2] (1), [Zn(L)(N3)2] (2), [Cu(L)(NCS)2] (3) and [Ni (L)(2bpy)(NCS)](ClO4) (4), [where L = N,N-dimethyl-N′-(phenyl-pyridin-2-yl-methylene)-ethane-1,2-diamine and 2bpy = 2-benzoylpyridine] were synthesized with the aim of investigating the role of different non-covalent weak interactions responsible for the crystal packing of the complexes. All of them were structurally characterised by X-ray diffraction analysis. In addition to conventional CH3⋯π and π⋯π interactions, the importance of unconventional C–H⋯π interactions in the crystal packing of compounds 1–4 was investigated by means of Hirshfeld surface analysis and DFT calculations. In these unconventional C–H⋯π interactions, the π-system (electron donor) is provided by the pseudohalide coligands. The interactions formed by the π-system depend on the nature of the pseudohalide (N3, NCO, NCS or NCSe) as demonstrated by molecular electrostatic potential calculations. Additionally, we have explored the photophysical properties of these complexes. Finally, we have combined a search in the Cambridge Structural Database and DFT energy calculations to analyse the rare ambidentate behaviour of SCN within the same complex.

Monotopic and heteroditopic calix[4]arene receptors as hosts for pyridinium and viologen ion pairs: a solution and solid-state study

The binding efficiency of a series of monotopic () and heteroditopic () calix[4]arene-based receptors has been evaluated in chloroform solution toward N-methylpyridinium ion pairs using NMR and UV/vis spectroscopic techniques. These experiments provided evidence that, due to a positive cooperative effect, the presence of a phenylurea H-bond donor group on the upper rim of the calix[4]arene macrocycle increases the recognition abilities of the heteroditopic receptors by up to two orders of magnitude with respect to the monotopic receptors. The heteroditopic receptors are also able to form 2:1 host-guest inclusion complexes with dimethylviologen salts both in low polarity solvents and in the solid state. These complexes are stabilized through the cooperation of weak (CH-pi and cation-pi) and strong (hydrogen bonding) intramolecular interactions between the binding domains of the calix[4]arene host and the two ions of the guest ion pair.

Crystallographic evidence of theoretically novel anion–π interactions

The reaction of Cu(NO3)2·3H2O with the multidentate ligand N,N′,N″,N‴-tetrakis{2,4-bis(di-2-pyridylamino)-1,3,5-triazin-6-yl} triethylenetetramine (dpatta) in acetonitrile at high temperature and pressure results in the formation of the tetranuclear coordination compound [Cu4(dpatta)(NO3)4](NO3)4·12H2O (1), whose crystal structure exhibits remarkable anion–π interactions which have been calculated, considering the unexpected position of the anion toward the aromatic ring.

Exclusive recognition of sarcosine in water and urine by a cavitand-functionalized silicon surface

A supramolecular approach for the specific detection of sarcosine, recently linked to the occurrence of aggressive prostate cancer forms, has been developed. A hybrid active surface was prepared by the covalent anchoring on Si substrates of a tetraphosphonate cavitand as supramolecular receptor and it was proven able to recognize sarcosine from its nonmethylated precursor, glycine, in water and urine. The entire complexation process has been investigated in the solid state, in solution, and at the solid–liquid interface to determine and weight all the factors responsible of the observed specificity. The final outcome is a Si-based active surface capable of binding exclusively sarcosine. The complete selectivity of the cavitand-decorated surface under these stringent conditions represents a critical step forward in the use of these materials for the specific detection of sarcosine and related metabolites in biological fluids.

Cavitand‐Grafted Silicon Microcantilevers as a Universal Probe for Illicit and Designer Drugs in Water

The direct, clean, and unbiased transduction of molecular recognition into a readable and reproducible response is the biggest challenge associated to the use of synthetic receptors in sensing. All possible solutions demand the mastering of molecular recognition at the solid-liquid interface as prerequisite. The socially relevant issue of screening amine-based illicit and designer drugs is addressed by nanomechanical recognition at the silicon-water interface. The methylamino moieties of different drugs are all first recognized by a single cavitand receptor through a synergistic set of weak interactions. The peculiar recognition ability of the cavitand is then transferred with high fidelity and robustness on silicon microcantilevers and harnessed to realize a nanomechanical device for label-free detection of these drugs in water.

Supramolecular Control of Single‐Crystal‐to‐Single‐Crystal Transformation through Selective Guest Exchange

Guest-switchable crystals: A solid-state guest exchange of the tetraphosphonate cavitand Tiiii[H,CH(3),Ph] as host promotes single-crystal-to-single-crystal transformations (see graphic). The strong preference for methanol over water is observed in all three phases (gas, liquid, solid), thus demonstrating the fundamental role played by the preorganized cavity through synergistic H-bonds and C-H⋅⋅⋅π interactions.