C. Daniel Varnado

Blind prediction of host-guest binding affinities: a new SAMPL3 challenge

The computational prediction of protein–ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands—i.e., host–guest systems—represent valuable test-beds for such affinity prediction methods, because their small size makes for fast calculations and relatively facile numerical convergence. The SAMPL3 community exercise included the first ever blind prediction challenge for host–guest binding affinities, through the incorporation of 11 new host–guest complexes. Ten participating research groups addressed this challenge with a variety of approaches. Statistical assessment indicates that, although most methods performed well at predicting some general trends in binding affinity, overall accuracy was not high, as all the methods suffered from either poor correlation or high RMS errors or both. There was no clear advantage in using explicit versus implicit solvent models, any particular force field, or any particular approach to conformational sampling. In a few cases, predictions using very similar energy models but different sampling and/or free-energy methods resulted in significantly different results. The protonation states of one host and some guest molecules emerged as key uncertainties beyond the choice of computational approach. The present results have implications for methods development and future blind prediction exercises.

Pyridine- and pyrimidine-functionalized poly(sulfone)s: performance-enhancing crosslinkers for acid/base blend proton exchange membranes used in direct methanol fuel cells

The direct methanol fuel cell (DMFC) is a promising energy conversion device that holds the potential to replace lithium ion batteries used in portable electronic devices. At present, widespread commercialization is impeded in part by the absence of a suitable proton exchange membrane (PEM). To address this need, pyridine- and pyrimidine-functionalized poly(sulfone)s (PPS and PMPS, respectively) were prepared in two high yielding post-polymerization C–H borylation/Suzuki coupling steps from commercially available UDEL® poly(sulfone). Membranes comprised of the aforementioned polymers blended with sulfonated poly(ether ether ketone) (SPEEK) were found to exhibit improved single cell performance and decreased methanol crossover in comparison to plain SPEEK and showed higher power densities than Nafion® 112, an exchange membrane commonly used in DMFCs. Blend properties and single cell performances were found to be dependent on the basicity and steric parameters of the N-heterocycle incorporated into the polymeric material used in the aforementioned membranes.

Electrochromic Poly(acetylene)s with Switchable Visible/Near-IR Absorption Characteristics

Ferrocene is incorporated into a poly(acetylene) derivative via the postpolymerization amidation of a polymer precursor bearing pentafluorophenyl ester-leaving groups with aminoferrocene. While the neutral polymer exhibits a strong absorbance at 553 nm due to its conjugated backbone, oxidation of the ferrocene moieties with silver tetrafluoroborate causes the material to absorb in the near-IR (λ max ≈ 1215 nm). Subsequent reduction of the oxidized polymer with decamethylferrocene restores the initial absorbance profile, demonstrating that the material features switchable visible/near-IR absorption characteristics.