Cyclodextrins (CDs) are cyclic oligosaccharides; the most common CDs contain six, seven, or eight glucose units called α-CDs, β-CDs, and γ-CDs, respectively. The use of CDs in biomedical research is increasing due to their ability to interact with membrane lipids as well as a wide variety of poorly water-soluble molecules. We assessed the impact of CD cavity size, occupancy, and substitutions on cytotoxicity and cholesterol homeostasis. The potency of CD-mediated cytotoxicity was in the order of β-CDs, α-CDs, and γ-CDs. Substitutions with hydroxypropyl or carboxymethyl group attenuated cytotoxicity compared with the native CDs, whereas CDs substituted with methyl groups exhibited cytotoxicity that was similar to that of the native CDs. The lipid components in blood exerted remarkable hemolysis-alleviating effects in methyl-β-CD-induced hemolysis. Occupancy of the CD cavity with cholesterol or a structurally related lipid molecule abrogated the cytotoxic capacity of the CDs. Interestingly, hydroxypropyl-γ-CD (HPγCD) was able to reduce intracellular cholesterol accumulation in Niemann–Pick disease type C (NPC) patient-derived fibroblasts as efficiently as HPβCD. Proteomic study indicated that HPβCD and HPγCD treatments altered the expression pattern of cellular proteins, suggesting that some of the CD-induced cellular proteins may play an important function in modulating intracellular cholesterol homeostasis.
The
introduction of functional groups with varying electron-donating/-withdrawing
properties at the β-position of diketopyrrolopyrrole (DPP) has
been shown to affect the optoelectronic properties of the polymers.
We report the synthesis of a new diketopyrrolopyrrole monomer wherein
a strong electron-donating substituent, a methoxy group, was incorporated
at the β-position in an effort to modulate polymer properties.
Homopolymers and co-polymers of the new β-methoxy DPP and nonderivatized
DPP were synthesized, and their properties were measured by cyclic
voltammetry and UV–vis–near-infrared. Density functional
theory computations also were employed to predict the degree of planarity
of β-methoxy oligomers to probe the significance of the newly
introduced S–O conformational lock. The combined experimental
and computational results showed a reduction in the gap between highest
occupied molecular orbital/lowest unoccupied molecular orbital levels,
a redshift toward the near-infrared region, and an increased planarity
in the β-methoxy polymers.
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