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1. Duplex Structure of Double-Stranded RNA Provides Stability against Hydrolysis Relative to Single-Stranded RNA

   https://doi.org/10.1021/acs.est.1c01255  

   Zhang, Ke; Hodge, Joseph; Chatterjee, Anamika; Moon, Tae Seok; Parker, Kimberly M. (May 2021, Environmental science technology)

   null (Ed.)

   Phosphodiester bonds in the backbones of double-stranded (ds)RNA and single-stranded (ss)RNA are known to undergo alkaline hydrolysis. Consequently, dsRNA agents used in emerging RNA interference (RNAi) products have been assumed to exhibit low chemical persistence in solutions. However, the impact of the duplex structure of dsRNA on alkaline hydrolysis has not yet been evaluated. In this study, we demonstrated that dsRNA undergoes orders-of-magnitude slower alkaline hydrolysis than ssRNA. Furthermore, we observed that dsRNA remains intact for multiple months at neutral pH, challenging the assumption that dsRNA is chemically unstable. In systems enabling both enzymatic degradation and alkaline hydrolysis of dsRNA, we found that increasing pH effectively attenuated enzymatic degradation without inducing alkaline hydrolysis that was observed for ssRNA. Overall, our findings demonstrated, for the first time, that key degradation pathways of dsRNA significantly differ from those of ssRNA. Consideration of the unique properties of dsRNA will enable greater control of dsRNA stability during the application of emerging RNAi technology and more accurate assessment of its fate in environmental and biological systems, as well as provide insights into broader application areas including dsRNA isolation, detection and inactivation of dsRNA viruses, and prebiotic molecular evolution. 

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2. Hybrid DNA/RNA nanostructures with 2′-5′ linkages

   https://doi.org/10.1039/d0nr05846g  

   Chandrasekaran, Arun Richard; Mathivanan, Johnsi; Ebrahimi, Parisa; Vilcapoma, Javier; Chen, Alan A.; Halvorsen, Ken; Sheng, Jia (November 2020, Nanoscale)

   null (Ed.)

   Nucleic acid nanostructures with different chemical compositions have shown utility in biological applications as they provide additional assembly parameters and enhanced stability. The naturally occurring 2′-5′ linkage in RNA is thought to be a prebiotic analogue and has potential use in antisense therapeutics. Here, we report the first instance of DNA/RNA motifs containing 2′-5′ linkages. We synthesized and incorporated RNA strands with 2′-5′ linkages into different DNA motifs with varying number of branch points (a duplex, four arm junction, double crossover motif and tensegrity triangle motif). Using experimental characterization and molecular dynamics simulations, we show that hybrid DNA/RNA nanostructures can accommodate interspersed 2′-5′ linkages with relatively minor effect on the formation of these structures. Further, the modified nanostructures showed improved resistance to ribonuclease cleavage, indicating their potential use in the construction of robust drug delivery vehicles with prolonged stability in physiological conditions. 

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3. Distance‐Dependent Energy Transfer Between Organic Fluorophores and Single‐Walled Carbon Nanotubes

   https://doi.org/10.1002/anie.202520411  

   Kamińska, Izabela; Metternich, Justus T; Szalai, Alan M; Smidoda, Carolin; Chakraborty, Sayantani; Vukovic, Lela; Kruss, Sebastian; Tinnefeld, Philip (March 2026, Angewandte Chemie International Edition)

   ABSTRACT Single‐walled carbon nanotubes (SWCNTs) are promising optical biosensing platforms due to their intrinsic near‐infrared fluorescence and environmental sensitivity. While DNA‐SWCNT hybrids have been widely studied, the structural arrangement of double‐stranded DNA (dsDNA) on SWCNTs and its impact on exciton–fluorophore interactions remain insufficiently characterized. Here, we introduce carbon nanotube energy transfer with vertical nucleic acids (CNETvNA), in which fluorophores are positioned at defined distances from SWCNTs using guanine‐defect anchored capture sequences hybridized with complementary oligonucleotides. By systematically varying the duplex length from 12 to 24 base pairs, we probe the distance dependence of dye–SWCNT interactions at the single‐molecule level. Fluorescence lifetime imaging microscopy reveals efficient quenching of ATTO542 and ATTO643 dyes, with lifetime distributions reflecting heterogeneous duplex conformations. Molecular dynamics simulations demonstrate that dsDNA duplexes adopt a predominantly perpendicular orientation relative to the SWCNT axis, with increasing tilt and conformational variability at longer lengths. Combining experimental and computational results, we establish a distance dependence of d⁻⁵with 7.4 ± 0.7 nm for 50% quenching efficiency, consistent with theoretical predictions for point dipole donors and 1D acceptors. These findings provide structural insights into DNA‐SWCNT conjugates and establish CNETvNA as a rational design principle for SWCNT‐based biosensors. 

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4. When Dihedral Angles Mask Denticity in Molecular Conductance

   https://doi.org/10.1002/cphc.202500816  

   Batzinger, Kevin; Dyer, Dylan; Peiris, M_D_Hashan C; El‐Assaad, Tarek H; Arachchige, Rashmi_Yohani Amarakoon; LaMotte, Sam; McGrath, Dominic V; Monti, Oliver LA; Smeu, Manuel (February 2026, ChemPhysChem)

   Stronger molecule–electrode coupling is associated with higher conductance in single‐molecule junctions. This has been taken to imply that more coordination—what will be referred to here as higher denticity—between the molecule and the electrode is expected to impart higher conductance to the overall junction. Herein, this assumption using a single molecule construct, a rigid N‐heterohexacene molecule with tetradentate ethyl sulfide (‐SEt) anchors, is examined. Thus, rather than comparing a series of molecules with different anchoring groups, it is investigated how variations in effective denticity arise naturally within one molecule. Using the nonequilibrium Green's function technique in conjunction with density functional theory and mechanically controlled break‐junction (MCBJ) experiments, it is found that increasing the denticity between the molecule and the electrode does not yield the expected higher conductance. Instead, simulated break‐junction traces reveal a strong correlation between conductance and the dihedral angle between the electrode and the molecular core, with changes to dihedral angles providing far more variation in conductance values than denticity alone. In fact, it is shown that counter to naïve expectations, different denticities cannot be distinguished by conductance, merging instead into a single conductance feature. This is supported by MCBJ experiments on this molecule, where only a single conductance state is identified, suggesting that the expected denticity‐dependent multistate conductance behavior is dominated by the effect of dihedral angles. By restricting dihedral angles to more favorable values by molecular design, the calculations show that significantly higher conductance values can still be achieved despite the limitations imposed by dihedral‐denticity coupling. The work demonstrates that mere denticity may not be sufficient to design highly conductive molecular junctions, and that the association of conductance features with different denticities should be treated with caution. 

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5. Filament assembly underpins the double-stranded DNA specificity of AIM2-like receptors

   https://doi.org/10.1093/nar/gkad090  

   Garg, Archit; Stallings, Christina M; Sohn, Jungsan (March 2023, Nucleic Acids Research)

   Abstract Upon sensing cytosolic- and/or viral double-stranded (ds)DNA, absent-in-melanoma-2 (AIM2)-like-receptors (ALRs) assemble into filamentous signaling platforms to initiate inflammatory responses. The versatile yet critical roles of ALRs in host innate defense are increasingly appreciated; however, the mechanisms by which AIM2 and its related IFI16 specifically recognize dsDNA over other nucleic acids remain poorly understood (i.e. single-stranded (ss)DNA, dsRNA, ssRNA and DNA:RNA hybrid). Here, we find that although AIM2 can interact with various nucleic acids, it preferentially binds to and assembles filaments faster on dsDNA in a duplex length-dependent manner. Moreover, AIM2 oligomers assembled on nucleic acids other than dsDNA not only display less ordered filamentous structures, but also fail to induce the polymerization of downstream ASC. Likewise, although showing broader nucleic acid selectivity than AIM2, IFI16 binds to and oligomerizes most readily on dsDNA in a duplex length-dependent manner. Nevertheless, IFI16 fails to form filaments on single-stranded nucleic acids and does not accelerate the polymerization of ASC regardless of bound nucleic acids. Together, we reveal that filament assembly is integral to nucleic acid distinction by ALRs. 

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