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This Full Paper investigates the adsorption and desorption of the anticancer drugs cis‐diamminedichloroplatinum(II) (CDDP, cisplatin) and the new platinum(II) complex di(ethylenediamineplatinum)medronate (DPM), as well as the clinically relevant bisphosphonate alendronate, towards two biomimetic synthetic HA nanocrystalline materials with either plate‐shaped (HAps) or needle‐shaped (HAns) morphologies and different chemico‐physical properties. The adsorption and desorption kinetics are dependent on the specific properties of the drugs and the morphology of the HA nanoparticles. Adsorption of the platinum complexes occurs with retention of the nitrogen ligands but the chloride ligands of cisplatin are displaced. Despite their opposite charges, the negatively charged alendronate bisphosphonate and the positively charged aquated cisplatin are strongly adsorbed, while the neutral DPM complex shows lower affinity towards the negatively charged apatitic surface. The data suggest that adsorption of the two platinum complexes is driven by electrostatic attractions, while interaction between the alendronate and the HA surface takes place by ligand exchange in which the two phosphonate groups of the drug molecule replace two surface phosphate groups. Significantly, adsorption of positively charged hydrolysis species of cisplatin is more favored on the phosphate‐rich HAns surface while adsorption of negatively charged alendronate is more favored on the calcium‐rich HAps surface. The latter type of short‐range electrostatic interactions also appear to dominate the desorption kinetics; consequently, drug release is greater for neutral DPM than for charged alendronate and aquated cisplatin. Moreover, while the release per unit area of charged species is the same for the two types of HAs, the release of DPM is faster from HAns, which is lower in surface calcium, than for HAps. Overall, this work demonstrates that the properties of HA nanocrystals can be modulated in such a way to produce HA/biomolecule conjugates tailored for specific therapeutic applications.

Synthetic amino acids such as fluorinated α-amino acids are currently actively investigated for their biological activity. Herein, we report on the synthesis and characterization of platinum complexes containing an N,O-chelated pure enantiomer of α-trifluoromethylalanine (α-Tfm-Ala). The compounds are either anionic, K[PtCl2(α-Tfm-Ala)], or cationic, [PtAm2(α-Tfm-Ala)](NO3) (Am2 = (NH3)2, ethylendiamine (en), 1,10-phenanthroline (phen), and 2,9-dimethyl-1,10-phenanthroline (Me2phen)). All complexes are highly soluble in water and have been fully characterized by NMR spectroscopy. In vitro cytotoxicity assays on different human tumor cell lines have been performed on some of the isolated compounds. [Pt(NH3)2(α-Tfm-Ala)] with R configuration of the amino acid proved to have an activity comparable to that of the reference compound cisplatin. Flow cytometric analysis on NCI-H460 tumor cells (absence of G2/M arrest, which instead is observed in the case of cisplatin) suggests a mechanism of action different from that of cisplatin.

The compounds [Pt(Me2phen)(acy)2](NO3)2 (1), [Pt(Me2phen)(pen)2](NO3)2, [Pt(phen)(acy)2](NO3)2 (2), and [Pt(phen)(pen)2](NO3)2, containing the bidentate 1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (Me2phen, neocuproine) and the antiviral agents acyclovir (acy) or penciclovir (pen), show different in vitro toxicity, the Me2phen complexes being appreciably more toxic than the phen complexes. To explain the different behavior, we investigated the reaction of complexes 1 and 2 with glutathione (γ-glutamylcysteinylglycine, GSH), a peptide believed to play an important role in driving the cellular effects of platinum drugs. The reaction led to different products, the phen complexes forming a stable binuclear μ-thiol-bridged species still containing the phenanthroline and the Me2phen complexes releasing the neocuproine ligand and forming an insoluble material. In vitro tests confirmed that the greater cell toxicity of complex 1 is due to the displacement of the neocuproine ligand by GSH. The results highlight the great dependence of the glutathione reactivity upon relatively small changes in the platinum coordination sphere.

Objective: To compare the efficacy of diet alone vs interdisciplinary therapy. Method: 256 women were divided into an interdisciplinary therapy group composed of 102 subjects and a control group composed of 154 subjects treated by means of diet alone. Results: 21.56% of the interdisciplinary group did not come for the 2 check-ups compared with 49.35% of the diet group (p>0.001). A weight loss of 5.88 kg and 4.18 kg for the interdisciplinary and the diet group was recorded 8 weeks after the start of the programme (second check-up). Discussion: Interdisciplinary therapy is necessary to personalize treatment and satisfy the patient’s desire and need for appropriate and effective management.

A novel case of polymorphism in platinum(II) complexes is reported. Single crystals of [PtBr2(2,9-dimethyl-1,10-phenanthroline)] were obtained at room temperature from a dilute dichloromethane/pentane (1:3, v/v) solution of the title compound in the presence of guanosine. The space group resulted to be Pbca[a= 20.4024(3), b= 20.3638(3), and c= 13.9522(2) Å, V= 5796.7(1) Å3, Z= 8]. Crystals of the same compound, obtained in slightly different conditions, had already been investigated by X-ray diffraction and found to have P21/nspace group, [a= 12.155(4), b= 7.933(2), and c = 14.522(2) Å, β= 93.74(2)°, V= 1397.3(6) Å3, Z= 4]. Comparison of the two polymorphous forms reveals huge differences in the crystal packing and the important role of the stacking interactions between phenanthroline ligands.

The present study evaluated impaired eating behaviour in women seeking participation in a diet-based programme of weight reduction or achievement of ideal body weight. Forty-seven obese, 42 overweight and 14 normal-weight subjects, attending an Italian university outpatient clinic completed the Eating Disorder Inventory (EDI). Forty-eight mothers of primary school children (25 normal-weight and 23 overweight) were used as controls. The EDI consists of 8 subscales, 3 evaluating psychopathology related to eating disorders (drive for thinness, bulimia, body dissatisfaction) and 5 evaluating general psychopathology (intereoceptive awareness, ineffectiveness, maturity fears, perfectionism, interpersonal distrust). Significantly altered scores in the first three subscales were observed both in normal-weight and overweight outpatients compared to the controls. The overweight oupatients scored higher than the obese patients in terms of drive for thinness and bulimia and higher than the normal-weight women for terms of bulimia, body dissatisfaction and drive for thinness. The overweight controls scored significantly higher than the normal-weight controls in the first three subscales in the remaining subscales, mean values were also higher in the overweight group, though significance was only reached in the interpersonal distrust and interoceptive awareness subscales. Impaired eating behaviour is frequent in subjects seeking participation in weight reduction or ideal body weight achievement programmes.