Sterically-Hindered Molecular p-Dopants Promote Integer Charge Transfer in Organic Semiconductors.

Molecular p-dopants designed to undergo electron transfer with organic semiconductors are typically planar molecules with high electron affinity. However, their planarity can promote the formation of ground-state charge transfer complexes with the semiconductor host and results in fractional instead of integer charge transfer, which is highly detrimental to doping efficiency. Here, we show this process can be readily overcome by targeted dopant design exploiting steric hindrance. To this end, we synthesize and characterize the remarkably stable p-dopant 2,2',2''-(cyclopropane-1,2,3-triylidene)tris(2-(perfluorophenyl)acetonitrile) comprising pendant functional groups that sterically shield its central core while retaining high electron affinity. Finally, we demonstrate it outperforms a planar dopant of identical electron affinity and increases the thin film conductivity by up to an order of magnitude. We believe exploiting steric hindrance represents a promising design strategy towards molecular dopants of enhanced doping efficiency.

Design, structure-activity relationship study and biological evaluation of the thieno[3,2-c]isoquinoline scaffold as a potential anti-cancer agent.

Several derivatives of a series that share a thienoisoquinoline scaffold have demonstrated potent activity against cancer cell lines A549, HeLa, HCT-116, and MDA-MB-231 in the submicromolar concentration range. Structure-activity relationship (SAR) studies on a range of derivatives aided in identifying key pharmacophores in the lead compound. A series of compounds have been identified as the most promising with submicromolar IC50 values against a lung cancer cell line (A549). Microscopy studies of cancer cells treated with the lead compound revealed that it causes mitotic arrest and disrupts microtubules. Further evaluation via an in vitro microtubule polymerization assay and competition studies indicate that the lead compound binds to tubulin via the colchicine site.

Approaching the Integer-Charge Transfer Regime in Molecularly Doped Oligothiophenes by Efficient Decarboxylative Cross-Coupling.

A library of symmetrical linear oligothiophene was prepared employing decarboxylative cross-coupling reaction as the key transformation. Thiophene potassium carboxylate salts were used as cross-coupling partners without the need of co-catalyst, base, or additives. This method demonstrates complete chemoselectivity and is a comprehensive greener approach compared to the existing methods. The modularity of this approach is demonstrated with the preparation of discreet oligothiophenes with up to 10 thiophene repeat units. Symmetrical oligothiophenes are prototypical organic semiconductors where their molecular electrical doping as a function of the chain length can be assessed spectroscopically. An oligothiophene critical length for integer charge transfer was observed to be 10 thiophene units, highlighting the potential use of discrete oligothiophenes as doped conduction or injection layers in organic electronics applications.

Preparation of a Convertible Spacer Containing a Disulfide Group for Versatile Functionalization of Oligonucleotides.

The protocols described in this article provide details regarding the synthesis and characterization of a disulfide containing linker phosphoramidite for terminal functionalization of synthetic oligonucleotides. The linker is first synthesized from 6-mercaptohexanol in two steps and is incorporated at the 5' end of short DNA oligonucleotides using automated solid-phase synthesis. The linker contains a terminal tosylate group which is post-synthetically displaced by altering the deprotection conditions to yield a variety of functional handles (N3 , NH2 , OMe, SH) or alternatively, the tosylate can be displaced directly with primary amines such as tert-butylamine. The linker system is also compatible with RNA oligonucleotides enabling the introduction of various functional handles (N3 , NH2 ). The protocol outlined in this procedure provides access to a versatile linker for the terminal functionalization of oligonucleotides containing a disulfide bond which may serve useful in the synthesis of reduction-responsive oligonucleotide conjugates. As a proof of concept, in this protocol the linker is used to modify a dT10 oligonucleotide and then conjugated by copper(I)-mediated azide-alkyne cycloaddition (CuAAC) to an alkyne-modified poly(ethylene glycol) which shows concentration dependent release of the oligonucleotide upon treatment with 1,4-dithiothreitol, a reducing agent. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparation of disulfide linker phosphoramidite 3 Basic Protocol 2: Synthesis, functionalization, and characterization of DNA oligonucleotides containing disulfide linker phosphoramidite 3 Basic Protocol 3: Displacement of terminal tosylate functionalized DNA with primary aliphatic amines Basic Protocol 4: Synthesis of oligonucleotide-PEG conjugate Support Protocol: Preparation of PEG-alkyne.

Influence of Backbone on the Performance of Pendant Polymer Electrode Materials in Li-ion Batteries.

Pendant polymers are a promising class of electrode materials due to their synthetic simplicity, derivation from sustainable feedstocks, and potentially benign synthesis. These materials consist of a redox-active pendant tethered to a polymer backbone, which mitigates dissolution during electrode cycling. To date, an extensive number of pendant groups have been studied within the context of metal-ion batteries. However, the choice of the polymer backbone and its impact on the electrode performance have been relatively understudied. In this work, we use a postpolymerization modification approach to synthesize a series of viologen-bearing redox-active pendant polymers with similar molecular weights but three distinct chemical backbones, namely, polyacrylamide, polymethacrylamide, and polystyryl. By evaluating the polymers in lithium-ion batteries, we show that the polymer backbone has a significant influence on electrode performance and behavior. Specifically, the polymethacrylamide displays slower kinetics than the other two polymers, resulting in lower capacities, particularly at high cycling rates. Furthermore, the charge storage mechanism is dependent on the nature of the backbone: the polyacrylamide shows a significant capacitive contribution to charge storage, while the polystyryl does not. The difference in performance between the polymer electrode materials is ascribed to a difference in chain mobility and packing within the electrode films. Overall, this work shows that the fundamental properties of the polymer backbone are critical to the design of high-performance polymer electrodes.

Synthesis of a Convertible Linker Containing a Disulfide Group for Oligonucleotide Functionalization.

The synthesis and incorporation of a tosylated phosphoramidite linker containing a disulfide bond is described. Incorporation of the linker into short DNA and RNA oligomers proceeded efficiently using automated solid phase synthesis. Treatment of the support bound oligonucleotide followed by cleavage from the solid support provided a variety of common functional handles, expanding the strategies of bifunctional modification of synthetic oligonucleotides for conjugation applications.

Characterization of a recently synthesized microtubule-targeting compound that disrupts mitotic spindle poles in human cells.

We reveal the effects of a new microtubule-destabilizing compound in human cells. C75 has a core thienoisoquinoline scaffold with several functional groups amenable to modification. Previously we found that sub micromolar concentrations of C75 caused cytotoxicity. We also found that C75 inhibited microtubule polymerization and competed with colchicine for tubulin-binding in vitro. However, here we found that the two compounds synergized suggesting differences in their mechanism of action. Indeed, live imaging revealed that C75 causes different spindle phenotypes compared to colchicine. Spindles remained bipolar and collapsed after colchicine treatment, while C75 caused bipolar spindles to become multipolar. Importantly, microtubules rapidly disappeared after C75-treatment, but then grew back unevenly and from multiple poles. The C75 spindle phenotype is reminiscent of phenotypes caused by depletion of ch-TOG, a microtubule polymerase, suggesting that C75 blocks microtubule polymerization in metaphase cells. C75 also caused an increase in the number of spindle poles in paclitaxel-treated cells, and combining low amounts of C75 and paclitaxel caused greater regression of multicellular tumour spheroids compared to each compound on their own. These findings warrant further exploration of C75's anti-cancer potential.