Unprecedented Relaxivity Gap in pH-Responsive FeIII-Based MRI Probes

Two mononuclear ferric complexes are reported that respond to a pH change with a 27- and 71-fold jump, respectively, in their capacity to accelerate the longitudinal relaxation rate of water-hydrogen nuclei, and this starting from a negligible base value of only 0.06. This unprecedented performance bodes well for tackling the sensitivity issues hampering the development of Molecular MRI. The two chelates also excel in the fully reversible and fatigue-less nature of this phenomenon. The structural reasons for this performance reside in the macrocyclic nature of the hexa-dentate ligand, as well as the presence of a single pendant arm displaying a five-membered lactam or carbamate which show (perturbed) pK_a values of 3.5 in the context of this N6 N5O1 coordination motif.     

Asymptotic sampling – a tool for efficient reliability computation in high dimensions

Monte Carlo methods are most versatile regarding applications to the reliability analysis of high-dimensional nonlinear structural systems. In addition to its versatility, the computational efficacy of Monte Carlo method is not adversely affected by the dimensionality of the problem. Crude Monte Carlo techniques, however, are very inefficient for extremely small failure probabilities such as typically required for sensitive structural systems. Therefore methods to increase the efficacy for small failure probability while keeping the adverse influence of dimensionality small are desirable. On such method is the asymptotic sampling method. Within the framework of this method, well-known asymptotic properties of the reliability index regarding the scaling of the basic variables are exploited to construct a regression model which allows to determine the reliability index for extremely small failure probabilities with high precision using a moderate number of Monte Carlo samples. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)