Summary: Fluoroquinolones are an important class of wide‐spectrum antibacterial agents. The first quinolone described was nalidixic acid, which showed a narrow spectrum of activity. The evolution of quinolones to more potent molecules was based on changes at positions 1, 6, 7 and 8 of the chemical structure of nalidixic acid. Quinolones inhibit DNA gyrase and topoisomerase IV activities, two enzymes essential for bacteria viability. The acquisition of quinolone resistance is frequently related to (i) chromosomal mutations such as those in the genes encoding the A and B subunits of the protein targets ( gyrA , gyrB , parC and parE ), or mutations causing reduced drug accumulation, either by a decreased uptake or by an increased efflux, and (ii) quinolone resistance genes associated with plasmids have been also described, i.e. the qnr gene that encodes a pentapeptide, which blocks the action of quinolones on the DNA gyrase and topoisomerase IV; the aac(6 ′ )‐Ib‐cr gene that encodes an acetylase that modifies the amino group of the piperazin ring of the fluoroquinolones and efflux pump encoded by the qepA gene that decreases intracellular drug levels. These plasmid‐mediated mechanisms of resistance confer low levels of resistance but provide a favourable background in which selection of additional chromosomally encoded quinolone resistance mechanisms can occur.

The review presents a broad overview of the biomedical applications of surface functionalized iron oxide nanoparticles (IONPs) as magnetic resonance imaging (MRI) agents for sensitive and precise diagnosis tool and synergistic combination with other imaging modalities. Then, the recent progress in therapeutic applications, such as hyperthermia is discussed and the available toxicity data of magnetic nanoparticles concerning in vitro and in vivo biomedical applications are addressed. This review also presents the available computer models using molecular dynamics (MD), Monte Carlo (MC) and density functional theory (DFT), as a basis for a complete understanding of the behaviour and morphology of functionalized IONPs, for improving NPs surface design and expanding the potential applications in nanomedicine.

Particle diffusion in crowded media was studied through Monte Carlo simulations in 3D obstructed lattices. Three particular aspects affecting the diffusion, not extensively treated in a three-dimensional geometry, were analysed: the relative particle-obstacle size, the relative particle-obstacle mobility and the way of having the obstacles distributed in the simulation space (randomly or uniformly). The results are interpreted in terms of the parameters that characterize the time dependence of the diffusion coefficient: the anomalous diffusion exponent (α), the crossover time from anomalous to normal diffusion regimes (τ) and the long time diffusion coefficient (D*). Simulation results indicate that there are a more anomalous diffusion (smaller α) and a lower long time diffusion coefficient (D*) when obstacle concentration increases, and that, for a given total excluded volume and immobile obstacles, the anomalous diffusion effect is less important for bigger size obstacles. However, for the case of mobile obstacles, this size effect is inverted yielding values that are in qualitatively good agreement with in vitro experiments of protein diffusion in crowded media. These results underline that the pattern of the spatial partitioning of the obstacle excluded volume is a factor to be considered together with the value of the excluded volume itself.

The interior of the living cell is highly concentrated and structured with molecules that have different shapes and sizes. Almost all experimental biochemical data have been obtained working in dilute solutions, situations which do not reflect the in vivo conditions. The consequences of such crowding upon enzymatic reactions remain unclear. In this paper, we have studied and compared the initial velocity of the hydrolysis of N-succinyl-L-phenyl-Ala-p-nitroanilide catalyzed by alpha-chymotrypsin, the oxidation of ABTS by H2O2 catalyzed by HRP and the oxidation of NADH in presence of pyruvate catalyzed by LDH. These reactions were chosen as model enzymatic processes occurring in different in vitro crowded media. The systems crowding has been built by introducing Dextran of several concentrations and sizes. Our results indicate that the volume occupied by the crowding agent, but not its size, plays an important role on the initial velocity of reactions involving tiny enzymes. However, the enzyme size is another important factor influencing the velocity of the reactions of large enzymes occurring in Dextran crowded media. In this situation, the reaction initial velocity depends on both occupied volume and dimension of the crowding agent that is present in the reaction media.

Traditionally, studies on the diffusion-controlled reaction of biological macromolecules have been carried out in dilute solutions (in vitro). However, in an intracellular environment (in vivo), there is a high concentration of macromolecules, which results in nonspecific interactions (macromolecular crowding). This affects the kinetics and thermodynamics of the reactions that occur in these systems. In this paper, we study the crowding effect of large macromolecules on the reaction rates of the hydrolysis of N-succinyl-L-phenyl-Ala-p-nitroanilide catalyzed by α-chymotrypsin, by adding dextrans of various molecular weights to the reaction solutions. The results indicate that the volume occupied by the crowding agent, but not its size, plays an important role in the rate of this reaction. A v_max decay and a K_m increase were obtained when the dextran concentration in the sample was increased. The increase in K_m can be attributed to the slowing of protein diffusion, due to the presence of crowding. Whereas the decrease in v_max could be explained by the effect of mixed inhibition by product, which is enhanced in crowded media. As far as we know, this is the first reported experiment on the crowding effect in an enzymatic reaction with a mixed inhibition by product.