Practical computational toolkits for dendrimers and dendrons structure design

Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface (GUI) toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.Peer reviewe

Design, Self-Assembly, and Switchable Wettability in Hydrophobic, Hydrophilic, and Janus Dendritic Ligand–Gold Nanoparticle Hybrid Materials

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Nanocrystal Core Size and Shape Substitutional Doping and Underlying Crystalline Order in Nanocrystal Superlattices

Substitutional doping is a potentially powerful technique to control the properties of nanocrystal (NC) superlattices (SLs). However, not every NC can be substituted into any lattice, as the NCs have to be close in size and shape, limiting the application of substitutional doping. Here we show that this limitation can be overcome by employing ligands of various size. We show that small NCs with long ligands can be substituted into SLs of big NCs with short ligands. Furthermore, we show that shape differences can also be overcome and that cubes can substitute spheres when both are coated with long ligands. Finally, we use the NC effective ligand size, softness, and effective overall size ratio to explain observed doping behaviors

Tuning the Electrocatalytic Oxygen Reduction Reaction Activity of Pt–Co Nanocrystals by Cobalt Concentration with Atomic-Scale Understanding

The development of a suitable catalyst for the oxygen reduction reaction (ORR), the cathode reaction of proton exchange membrane fuel cells (PEMFC), is necessary to push this technology toward widespread adoption. There have been substantial efforts to utilize bimetallic Pt−M alloys that adopt the ordered face-centered tetragonal (L10) phase in order to reduce the usage of precious metal, enhance the ORR performance, and improve catalyst stability. In this work, monodisperse Pt–Co nanocrystals (NCs) with well-defined size (4–5 nm) and cobalt composition (25–75 at%) were synthesized via colloidal synthesis. The transformation from the chemically disordered A1 (face-centered cubic, fcc) to the L10 phase was achieved via thermal annealing using both a conventional oven and a rapid thermal annealing process. The structure of the Pt–Co catalysts was characterized by a variety of techniques, including transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy in high-angle annular dark-field scanning transmission electron microscopy (STEM-EDS), small-angle X-ray scattering (SAXS), X-ray diffraction (XRD), and inductively coupled plasma–optical emission spectrometry (ICP-OES). The effects of annealing temperature on the composition-dependent degree of ordering and subsequent effect on ORR activity is described. This work provides insights regarding the optimal spatial distribution of elements at the atomic level to achieve enhanced ORR activity and stability

Differential Potency of 2,6-Dimethylcyclohexanol Isomers for Positive Modulation of GABAA Receptor Currents

GABAA receptors meet all of the pharmacological requirements necessary to be considered important targets for the action of general anesthetic agents in the mammalian brain. In the following patch-clamp study, the relative modulatory effects of 2,6-dimethylcyclohexanol diastereomers were investigated on human GABAA (a1b3g2s) receptor currents stably expressed in human embryonic kidney cells. Cis,cis-, trans,trans-, and cis, trans-isomers were isolated from commercially available 2,6- dimethylcyclohexanol and were tested for positive modulation of submaximal GABA responses. For example, the addition of 30 mM cis,cis-isomer resulted in an approximately 2- to 3-fold enhancement of the EC20 GABA current. Coapplications of 30 mM 2,6-dimethylcyclohexanol isomers produced a range of positive enhancements of control GABA responses with a rank order for positive modulation: cis,cis . trans,trans $ mixture of isomers . . cis,transisomer. In molecular modeling studies, the three cyclohexanol isomers bound with the highest binding energies to a pocket within transmembrane helices M1 and M2 of the b3 subunit through hydrogen-bonding interactions with a glutamine at the 224 position and a tyrosine at the 220 position. The energies for binding to and hydrogen-bond lengths within this pocket corresponded with the relative potencies of the agents for positive modulation of GABAA receptor currents (cis,cis . trans,trans . cis,trans-2,6-dimethylcyclohexanol). In conclusion, the stereochemical configuration within the dimethylcyclohexanols is an important molecular feature in conferring positive modulation of GABAA receptor activity and for binding to the receptor, a consideration that needs to be taken into account when designing novel anesthetics with enhanced therapeutic indices

Nanocrystal core size and shape substitutional doping and underlying crystalline order in nanocrystal superlattices

Substitutional doping is a potentially powerful technique to control the properties of nanocrystal (NC) superlattices (SLs). However, not every NC can be substituted into any lattice, as the NCs have to be close in size and shape, limiting the application of substitutional doping. Here we show that this limitation can be overcome by employing ligands of various size. We show that small NCs with long ligands can be substituted into SLs of big NCs with short ligands. Furthermore, we show that shape differences can also be overcome and that cubes can substitute spheres when both are coated with long ligands. Finally, we use the NC effective ligand size, softness, and effective overall size ratio to explain observed doping behaviors