Three novel tetracationic bis‐triarylboranes with 3,4‐ethylenedioxythiophene (EDOT) linkers, and their neutral precursors, showed significant red‐shifted absorption and emission compared to their thiophene‐containing analogues, with one of the EDOT‐derivatives emitting in the NIR region. Only the EDOT‐linked trixylylborane tetracation was stable in aqueous solution, indicating that direct attachment of a thiophene or even 3‐methylthiophene to the boron atom is insufficient to provide hydrolytic stability in aqueous solution. Further comparative analysis of the EDOT‐linked trixylylborane tetracation and its bis‐thiophene analogue revealed efficient photo‐induced singlet oxygen production, with the consequent biological implications. Thus, both analogues bind strongly to ds‐DNA and BSA, very efficiently enter living human cells, accumulate in several different cytoplasmic organelles with no toxic effect but, under intense visible light irradiation, they exhibit almost instantaneous and very strong cytotoxic effects, presumably attributed to singlet oxygen production. Thus, both compounds are intriguing theranostic agents, whose intracellular and probably intra‐tissue location can be monitored by strong fluorescence, allowing switching on of the strong bioactivity by well‐focused visible light.

The BSA-encapsulated gold nanoclusters (AuNC@BSA) have drawn considerable interest and demonstrated applications as biological sensors. In this study, we demonstrated that the red-emitting AuNC@BSA prepared using a modified procedure fully retained the binding of standard BSA-ligands (small molecule drugs), significantly improving fluorescence detection in some cases due to the red-emission property. Further, we showed that AuNC@BSA efficiently bind a series of aflatoxin-related mycotoxins as well as the aliphatic mycotoxin FB₁, reporting interactions in the nanomolar range by instantaneous emission change at 680 nm. Such red emission detection is advantageous over current detection strategies for the same mycotoxins, based on complex mass spectrometry procedures or, eventually (upon chemical modification of the mycotoxin), by fluorescence detection in the UV range (<400 nm). The later technique yields fluorescence strongly overlapping with the intrinsic absorption and emission of biorelevant mixtures in which mycotoxins appear. Thus, here we present a new approach using the AuNC@BSA red fluorescence reporter for mycotoxins as a fast, cheap, and simple detection technique that offers significant advantages over currently available methods.

Four novel peptidoids, derived from the Phe-Arg-His (FRH) peptide motif, were prepared by replacing the histidine heterocycle with triazole and consequent triazole-fluorophore (coumarin) extension and also replacing arginine with less voluminous lysine. So the constructed Phe-Lys-Ala(triazole) (FKA(triazole)) peptidoids bind Cu²⁺ cations in water with a strong, nanomolar affinity comparable to the parent FRH and its known analogs, demonstrating that triazole can coordinate copper similarly as histidine. Moreover, even short KA(triazole)coumarin showed submicromolar affinity to Cu²⁺. Only FKA(triazole)coumarin with free amino groups and its shorter analog KA(triazole)coumarin showed strong induced CD spectra upon Cu²⁺ cation binding. Thus, KA(triazole)coumarin can be considered as the shortest peptidoid sequence with highly sensitive fluorescent and chiral CD response for Cu²⁺ cation, encouraging further studies with other metal cations. The FKA(triazole) coumarin peptidoids show biorelevant, 10 µM affinity to ds-DNA and ds-RNA, binding within DNA/RNA grooves. Intriguingly, only peptidoid complexes with Cu²⁺ strongly stabilize ds-DNA and ds-RNA against thermal denaturation, suggesting significant interactions of Cu²⁺ cation within the DNA/RNA binding site.

The 2- and 2,7- substituted para-N-methylpyridinium pyrene cations show high-affinity intercalation into ds-DNAs, whereas their non-methylated analogues interacted with ds-DNA/RNA only in the protonated form (at pH 5), but not at physiological conditions (pH 7). The fluorescence from non-methylated analogues was strongly dependent on the protonation of the pyridines; consequently, they act as fluorescence ratiometric probes for simultaneous detection of both ds-DNA and BSA at pH 5, relying on the ratio between intensities at 420 nm (BSA specific) and 520 nm (DNA specific), whereby exclusively ds-DNA sensing could be switched-off by adjustment to pH 7. Only methylated, permanently charged pyrenes show photoinduced cleavage of circular DNA, attributed to pyrene-mediated irradiation-induced production of singlet oxygen. Consequently, the moderate toxicity of these cations against human cell lines is strongly increased upon irradiation. Detailed studies revealed increased total ROS production in cells treated by the compounds studied, accompanied by cell swelling and augmentation of cellular complexity. The most photo-active 2-para-N-methylpyridinium pyrene showed significant localization at mitochondria, its photo-bioactivity likely due to mitochondrial DNA damage. Other derivatives were mostly non-selectively distributed between various cytoplasmic organelles, thus being less photoactive.

In three novel peptidoids based on the tryptophan—histidine—tryptophan (WHW) peptide, the central histidine was replaced by Ala-(triazole), and two derivatives also had one tryptophan replaced with pyrene-alkyls of different lengths and flexibility. Pyrene analogues show strong fluorescence at 480–500 nm, attributed to intramolecular exciplex formation with tryptophan. All three peptidoids bind Cu²⁺ cation in water with strong affinity, with Trp- Ala-(triazole)-Trp binding comparably to the parent WHW, and the pyrene analogues even stronger, demonstrating that replacement of histidine with triazole in peptides does not hamper Cu²⁺ coordination. The studied peptidoids strongly bind to ds-DNA and ds-RNA, whereby their complexes with Cu²⁺ exhibit distinctively different interactions in comparison to metal-free analogues, particularly in the stabilization of ds-DNA against thermal denaturation. The pyrene peptidoids efficiently enter living cells with no apparent cytotoxic effect, whereby their red-shifted emission compared to the parent pyrene allows intracellular confocal microscopy imaging, showing accumulation in cytoplasmic organelles. However, irradiation with 350 nm light resulted in evident antiproliferative effect on cells treated with micromolar concentrations of the pyrene analogues, presumably attributed to pyrene-induced production of singlet oxygen and consecutive cellular damage.