De Novo Design of Selective Quadruplex–Duplex Junction Ligands and Structural Characterisation of Their Binding Mode: Targeting the G4 Hot-Spot

Targeting the interface between DNA quadruplex and duplex regions by small molecules holds significant promise in both therapeutics and nanotechnology. Herein, a new pharmacophore is reported, which selectively binds with high affinity to quadruplex–duplex junctions, while presenting a poorer affinity for G-quadruplex or duplex DNA alone. Ligands complying with the reported pharmacophore exhibit a significant affinity and selectivity for quadruplex–duplex junctions, including the one observed in the HIV-1 LTR-III sequence. The structure of the complex between a quadruplex–duplex junction with a ligand of this family has been determined by NMR methods. According to these data, the remarkable selectivity of this structural motif for quadruplex–duplex junctions is achieved through an unprecedented interaction mode so far unexploited in medicinal and biological chemistry: the insertion of a benzylic ammonium moiety into the centre of the partially exposed G-tetrad at the interface with the duplex. Further decoration of the described scaffolds with additional fragments opens up the road to the development of selective ligands for G-quadruplex-forming regions of the genome.     

Microfluidic Production of Pyrophosphate Catalyzed by Mineral Membranes with Steep pH Gradients

Pyrophosphate might have functioned as an energy storage/currency molecule on early Earth, essential for the emergence of life. Here we synthesized mineral membranes involving iron(II), iron(III), and other divalent metal cations (calcium, manganese, cobalt, copper, zinc, and nickel) and tested their ability to catalyze the formation of pyrophosphate from phosphate and acetyl phosphate across steep pH gradients in microfluidic devices. We studied the chemical compositions of the precipitate membranes (which included vivianite, goethite, and green rust) using in situ and ex situ micro-Raman spectroscopy. The yields of pyrophosphate were determined by aqueous ³¹P NMR spectroscopy. We found that Fe²⁺ and Ca²⁺ were the best catalysts for pyrophosphate synthesis among investigated ions; Fe³⁺ and mixed-valence iron membranes were also able to promote pyrophosphate formation. In addition, the pH gradients across the membranes affected the pyrophosphate yields and the smallest pH gradient resulted in the highest yield. These results suggest a possible route of substrate phosphorylation in prebiotic hydrothermal systems.     

Photoinduced Electron Transfer Involving a Naphthalimide Chromophore in Switchable and Flexible [2]Rotaxanes

The interlocking of ring and axle molecular components in rotaxanes provides a way to combine chromophoric, electron-donor and electron-acceptor moieties in the same molecular entity, in order to reproduce the features of photosynthetic reaction centers. To this aim, the photoinduced electron transfer processes involving a 1,8-naphthalimide chromophore, embedded in several rotaxane-based dyads, were investigated by steady-state and time-resolved absorption and luminescence spectroscopic experiments in the 300 fs–10 ns time window. Different rotaxanes built around the dialkylammonium/ dibenzo[24]crown-8 ether supramolecular motif were designed and synthesized to decipher the relevance of key structural factors, such as the chemical deactivation of the ammonium-crown ether recognition, the presence of a secondary site for the ring along the axle, and the covalent functionalization of the macrocycle with a phenothiazine electron donor. Indeed, the conformational freedom of these compounds gives rise to a rich dynamic behavior induced by light and may provide opportunities for investigating and understanding phenomena that take place in complex (bio)molecular architectures.     

Atomistic simulation of the interaction of slow protons with an iron surface

Summary We have studied the dynamical behaviour of low-energy protons (1.0 eV≤E _in≤50 eV) interacting with a Fe {100} surface atT=300 K, by means of molecular-dynamics simulations. The inelastic energy losses have been taken into account by means of a friction term proportional to the projectile velocity and depending on the instantaneous local electronic density experienced by the projectile. For a given incident energy and irradiation geometry, we have estimated the particle and energy reflection coefficients and obtained a detailed evaluation of the different contributions (elastic and inelastic) to the energy loss of the reflected particles.     

A tandem Petasis-Ugi multi component condensation reaction: solution phase synthesis of six dimensional libraries

Amino acids with three points of diversity generated from the Petasis boronic acid-Mannich reaction can be used as one of the four components of the Ugi condensation to prepare six dimensional libraries of dipeptide amides.     

The Brera Tower air quality monitoring station

Summary The characteristics of the air quality monitoring station of Brera Tower are described. The station is focused on the study of air pollution in the urban area and on the aerosol chemistry and reactivity in the atmosphere. The influence of meteorological parameters is also taken into account. Results about the concentration, the chemical composition and the size distribution of suspended particulate matter and about the ionic composition and acidity of rain are also presented. Paper presented at the IV Congresso del Gruppo Nazionale per la Fisica dell'Atmosfera e dell'Oceano, June 22–24, 1987, Rome.