Unlocking the full evolutionary potential of artificial metalloenzymes through direct metal-protein coordination: A review of recent advances for catalyst development

Generation of artificial metalloenzymes (ArMs) has gained much inspiration from the general understanding of natural metalloenzymes. Over the last decade, a multitude of methods generating transition metal-protein hybrids have been developed and many of these new-to-nature constructs catalyse reactions previously reserved for the realm of synthetic chemistry. This perspective will focus on ArMs incorporating 4d and 5d transition metals. It aims to summarise the significant advances made to date and asks whether there are chemical strategies, used in nature to optimise metal catalysts, that have yet to be fully recognised in the synthetic enzyme world, particularly whether artificial enzymes produced to date fully take advantage of the structural and energetic context provided by the protein. Further, the argument is put forward that, based on precedence, in the majority of naturally evolved metalloenzymes the direct coordination bonding between the metal and the protein scaffold is integral to catalysis. Therefore, the protein can attenuate metal activity by positioning ligand atoms in the form of amino acids, as well as making non-covalent contributions to catalysis, through intermolecular interactions that pre-organise substrates and stabilise transition states. This highlights the often neglected but crucial element of natural systems that is the energetic contribution towards activating metal centres through protein fold energy. Finally, general principles needed for a different approach to the formation of ArMs are set out, utilising direct coordination inspired by the activation of an organometallic cofactor upon protein binding. This methodology, observed in nature, delivers true interdependence between metal and protein. When combined with the ability to efficiently evolve enzymes, new problems in catalysis could be addressed in a faster and more specific manner than with simpler small molecule catalysts.</jats:p

In-street wind direction variability in the vicinity of a busy intersection in central London

We present results from fast-response wind measurements within and above a busy intersection between two street canyons (Marylebone Road and Gloucester Place) in Westminster, London taken as part of the DAPPLE (Dispersion of Air Pollution and Penetration into the Local Environment; www.dapple.org.uk) 2007 field campaign. The data reported here were collected using ultrasonic anemometers on the roof-top of a building adjacent to the intersection and at two heights on a pair of lamp-posts on opposite sides of the intersection. Site characteristics, data analysis and the variation of intersection flow with the above-roof wind direction (θref) are discussed. Evidence of both flow channelling and recirculation was identified within the canyon, only a few metres from the intersection for along-street and across-street roof-top winds respectively. Results also indicate that for oblique rooftop flows, the intersection flow is a complex combination of bifurcated channelled flows, recirculation and corner vortices. Asymmetries in local building geometry around the intersection and small changes in the background wind direction (changes in 15-min mean θref of 5–10 degrees) were also observed to have profound influences on the behaviour of intersection flow patterns. Consequently, short time-scale variability in the background flow direction can lead to highly scattered in-street mean flow angles masking the true multi-modal features of the flow and thus further complicating modelling challenges

On the nonequilibrium entropy of large and small systems

Thermodynamics makes definite predictions about the thermal behavior of macroscopic systems in and out of equilibrium. Statistical mechanics aims to derive this behavior from the dynamics and statistics of the atoms and molecules making up these systems. A key element in this derivation is the large number of microscopic degrees of freedom of macroscopic systems. Therefore, the extension of thermodynamic concepts, such as entropy, to small (nano) systems raises many questions. Here we shall reexamine various definitions of entropy for nonequilibrium systems, large and small. These include thermodynamic (hydrodynamic), Boltzmann, and Gibbs-Shannon entropies. We shall argue that, despite its common use, the last is not an appropriate physical entropy for such systems, either isolated or in contact with thermal reservoirs: physical entropies should depend on the microstate of the system, not on a subjective probability distribution. To square this point of view with experimental results of Bechhoefer we shall argue that the Gibbs-Shannon entropy of a nano particle in a thermal fluid should be interpreted as the Boltzmann entropy of a dilute gas of Brownian particles in the fluid

Boundary Terms and Junction Conditions for Generalized Scalar-Tensor Theories

We compute the boundary terms and junction conditions for Horndeski's panoptic class of scalar-tensor theories, and write the bulk and boundary equations of motion in explicitly second order form. We consider a number of special subclasses, including galileon theories, and present the corresponding formulae. Our analysis opens up of the possibility of studying tunnelling between vacua in generalized scalar-tensor theories, and braneworld dynamics. The latter follows because our results are independent of spacetime dimension.Comment: 13 pages, Equation corrected. Thanks to Tsutomu Kobayashi for informing us of the typ