An In Vitro Study on the Application of Silver-Doped Platelet-Rich Plasma in the Prevention of Post-Implant-Associated Infections.

Implant therapy is a common treatment option in dentistry and orthopedics, but its application is often associated with an increased risk of microbial contamination of the implant surfaces that cause bone tissue impairment. This study aims to develop two silver-enriched platelet-rich plasma (PRP) multifunctional scaffolds active at the same time in preventing implant-associated infections and stimulating bone regeneration. Commercial silver lactate (L) and newly synthesized silver deoxycholate:ß-Cyclodextrin (B), were studied in vitro. Initially, the antimicrobial activity of the two silver soluble forms and the PRP enriched with the two silver forms has been studied on microbial planktonic cells. At the same time, the biocompatibility of silver-enriched PRPs has been assessed by an MTT test on human primary osteoblasts (hOBs). Afterwards, an investigation was conducted to evaluate the activity of selected concentrations and forms of silver-enriched PRPs in inhibiting microbial biofilm formation and stimulating hOB differentiation. PRP-L (0.3 µg/mm2) and PRP-B (0.2 µg/mm2) counteract Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans planktonic cell growth and biofilm formation, preserving hOB viability without interfering with their differentiation capability. Overall, the results obtained suggest that L- and B-enriched PRPs represent a promising preventive strategy against biofilm-related implant infections and demonstrate a new silver formulation that, together with increasing fibrin binding protecting silver in truncated cone-shaped cyclic oligosaccharides, achieved comparable inhibitory results on prokaryotic cells at a lower concentration.

[Gd(HB-DO3A)]: Equilibrium, Dissociation Kinetic and Structural Differences in a Simple Homolog of [Gd(HP-DO3A)] (Prohance®).

[Gd(HP-DO3A)] (gadoteridol) as an active compound of ProHance® is a widely employed contrast agent in clinical MRI scans in the last 30 years. Recent concerns about the long-term retention of gadolinium-based contrast agents (GBCAs) led to a deeper investigation of the structural features underlying the integrity of the paramagnetic metal complex. Several human and nonclinical studies have noted marked differences among the macrocyclic GBCAs, with the least retention of Gd traces and most rapid elimination consistently being reported for [Gd(HP-DO3A)]. It was deemed of interest to assess how minor structural/electronic changes associated to the ligand structure may affect basic properties of the metal complex with several [Gd(HP-DO3A)] analogues synthesized and characterized in the last years. We recently reported that the closest homolog of [Gd(HP-DO3A)], i. e.: [Gd(HB-DO3A)], in which a (±)-2-hydroxy-1-propyl pendant arm is replaced by a (±)-2-hydroxy-1-butyl moiety, showed a significantly different retention behaviour in the model interaction with collagen, despite the apparently very minor structural difference. In this paper we report a comprehensive study of the structural, thermodynamic, kinetic and relaxation properties of [Gd(HB-DO3A)], compared to the parent [Gd(HP-DO3A)] and to other closely related macrocyclic GBCAs to assess whether very minor structural changes can modulate the physico-chemical properties of Gd3+ complexes.

EHDTA: a green approach to efficient Ln3+-chelators.

The rich coordination chemistry of lanthanoid ions (Ln3+) is currently exploited in a vast and continuously expanding array of applications. Chelating agents are central in the development of Ln3+-complexes and in tuning their physical and chemical properties. Most chelators for Ln3+-complexation are derived from the macrocyclic DOTA or from linear DTPA platforms, both of which arise from fossil-based starting materials. Herein, we report a green and efficient approach to a chelating agent (EHDTA), derived from cheap and largely available furfurylamine. The oxygenated heterocycle of the latter is converted to a stereochemically defined and rigid heptadentate chelator, which shows good affinity towards Ln3+ ions. A combination of NMR, relaxometric, potentiometric and spectrophotometric techniques allows us to shed light on the interesting coordination chemistry of Ln3+-EHDTA complexes, unveiling a promising ligand for the chelation of this important family of metal ions.

Grafting Going Green: Toward a Sustainable Preparation of Organic-Inorganic Hybrid Materials.

Organic-inorganic hybrid materials find many applications in catalysis, nanotechnology, electronics, and many others. Grafting organic functionalities on inorganic supports is one of the most used methods for their preparation. Toluene is the solvent of choice for the grafting reaction, but it is fossil fuel-derived and not devoid of toxic effects. In this work, we explore the use of sustainable alternatives, i.e., (+)-α-pinene, (-)-ß-pinene, dimethyl carbonate (DMC), (+)-limonene, and 2-methyl-tetrahydrofuran (MeTHF), as solvents for grafting. The grafting reaction between 3-aminopropyltriethoxysilane (APTS) and mesoporous ordered silica (MCM-41) was selected as a model for this study. A comparison of the rate of the grafting reaction in different solvents is reported. The resulting hybrid materials were analyzed by Fourier-transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA) and compared to the reference material prepared in toluene. MeTHF proved to be the best sustainable alternative to toluene for model grafting, providing a comparable product in a significantly shorter reaction time.

Boosting Bismuth(III) Complexation for Targeted α-Therapy (TAT) Applications with the Mesocyclic Chelating Agent AAZTA.

Targeted α therapy (TAT) is a promising tool in the therapy of cancer. The radionuclide 213 BiIII shows favourable physical properties for this application, but the fast and stable chelation of this metal ion remains challenging. Herein, we demonstrate that the mesocyclic chelator AAZTA quickly coordinates BiIII at room temperature, leading to a robust complex. A comprehensive study of the structural, thermodynamic and kinetic properties of [Bi(AAZTA)]- is reported, along with bifunctional [Bi(AAZTA-C4-COO- )]2- and the targeted agent [Bi(AAZTA-C4-TATE)]- , which incorporates the SSR agonist Tyr3 -octreotate. An unexpected increase in the stability and kinetic inertness of the metal chelate was observed for the bifunctional derivative and was maintained for the peptide conjugate. A cyclotron-produced 205/206 Bi mixture was used as a model of 213 Bi in labelling, stability, and biodistribution experiments, allowing the efficiency of [213 Bi(AAZTA-C4-TATE)]- to be estimated. High accumulation in AR42J tumours and reduced kidney uptake were observed with respect to the macrocyclic chelate [213 Bi(DOTA-TATE)]- .

Predicting the Conformation of Organic Catalysts Grafted on Silica Surfaces with Different Numbers of Tethering Chains: The Silicopodality Concept.

Hybrid catalysts are attracting much attention, since they combine the versatility and efficiency of homogeneous organic catalysis with the robustness and thermal stability of solid materials, for example, mesoporous silica; in addition, they can be used in cascade reactions, for exploring both organic and inorganic catalysis at the same time. Despite the importance of the organic/inorganic interface in these materials, the effect of the grafting architecture on the final conformation of the organic layer (and hence its reactivity) is still largely unexplored. Here, we investigate a series of organosiloxanes comprising a pyridine ring (the catalyst model) and different numbers of alkylsiloxane chains used to anchor it to the MCM-41 surface. The hybrid interfaces are characterized with X-ray powder diffraction, thermogravimetric analyses, Fourier-transform infrared spectroscopy, nuclear magnetic resonance techniques and are modeled theoretically through molecular dynamics (MD) simulations, to determine the relationship between the number of chains and the average position of the pyridine group; MD simulations also provide some insights about temperature and solvent effects.

Interaction of macrocyclic gadolinium-based MR contrast agents with Type I collagen. Equilibrium and kinetic studies.

The interactions of gadoterate meglumine, gadobutrol, gadoteridol and Gd(HB-DO3A) with bovine Type I collagen were investigated by ultrafiltration and dialysis. The affinity of the four agents to collagen is similar. However, the maximum adsorbed amount of GdIII-complexes decreases in the following order: gadoterate meglumine > gadobutrol > gadoteridol > Gd(HB-DO3A). Calculations with the open three-compartment model reveal that the structural homologs gadoteridol and Gd(HB-DO3A) have a lower adsorption onto collagen, which may explain the less prolonged in vivo retention of gadoteridol observed in soft tissues of rats.

A Successful Replacement of Phenols with Isocyanides in the Bargellini Reaction: Synthesis of 3-Carboxamido-Isobutyric Acids.

Old multicomponent reactions are still a source of inspiration for discovering novel combinations of three or more reactants. A simple idea is to replace one of the educts of a known multicomponent reaction with another functional group and still be able to mimic the same reactivity. Following this line of thought, we report a three-component reaction in which isocyanides are able to open the epoxide intermediate of the Bargellini reaction affording 3-carboxamido-isobutyric acids in yields of 47-95%.