DNA alkylating agents are widely used in anticancer pharmacology. Although shown to induce cross-linking and/or methylation of DNA, how they affect the mechanical properties of DNA and activity of DNA enzymes remains to be elucidated. Here, we perform single-molecule optical tweezer experiments on DNA treated with alkylating agents, including melphalan, cisplatin, and dacarbazine. While all three drugs induce a significant increase of overstretching force and a reduction of hysteresis, suggesting stabilization of DNA against shearing forces, their effects on elasticity of DNA were quite different, with the largest change in persistence length induced by cisplatin. Furthermore, we find that these alkylating-agent-induced changes on DNA have different effects on processivity of DNA polymerase, with melphalan and cisplatin showing significantly reduced activity and dacarbazine showing little effect. Overall, our results provide new insights into the effects for these alkylating agents, which could potentially facilitate a better design of related drugs.
Polymers of intrinsic microporosity (PIMs) are promising materials for membrane separation because their special rigid and contorted structures contribute to high permeability. However, their chain rearrangement to fill excessive free volume makes the permeability stability a tough challenge. In this work, we report on a new use of rutile nano-TiO 2 to mitigate the physical aging of PIM-1 (a typical PIM) nanofilms for stable permeability by mixing matrix. It was shown that the PIM-1 membrane incorporated with nano-TiO 2 displayed remarkably higher aging resistance with a lower swelling degree in long-term ethanol soaking, having more stable ethanol permeance with only a 5% decrease after 35 days, lower than 25% of the pure one. The mechanism of anti-aging was revealed by molecular simulation, thermal, tensile mechanical, and dynamic mechanical analysis. It was found that nano-TiO 2 had good compatibility with PIM-1 due to strong coordination interaction, making its uniform dispersion in polymer. Additional solvent permeation channels were also created to increase solvent permeance without compromising solute rejection. Due to the reliable interaction of nano-TiO 2 , which makes particles serve as physical crosslinking points, the movement of PIM-1 chains was limited partially to mitigate aging, enabling PIM-1-based membranes to have robust solvent permeation. Graphical
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