Self-assembled monolayers (SAMs) are frequently used for work function (WF) engineering of different materials. For this, typically dipolar groups are attached to the molecule terminus at the SAM–ambient interface, which also influences its chemistry. WF engineering and interface chemistry can, however, be decoupled from one another using embedded dipolar groups, as has been demonstrated before for thiolate SAMs on metals. Herein, we extend this concept to oxide substrates. For this, a series of biphenyl-based molecules with a phosphonic acid (PA) anchoring group was synthesized, with one of the nonpolar phenyl units exchanged for a polar pyrimidine moiety, the dipole moment of which is oriented either toward (“down”) or away (“up”) to/from the PA group and, consequently, to/from the substrate. SAMs of these molecules formed on indium tin oxide (ITO), a frequently used and application-relevant oxide substrate, feature a uniform molecular configuration, dense molecular packing, and an upright molecular orientation. These SAMs exhibit pronounced electrostatic effects associated with the embedded dipolar groups, viz. shifts of the characteristic peaks in the C 1s X-ray photoelectron spectra and WF variations. The latter values were found to be 3.9, 4.85, and 4.4 eV for the up, down, and nonpolar reference SAM-engineered ITO, respectively. Consequently, these SAMs can serve as a powerful tool to monitor WF engineering effects in a variety of device assembles, decoupling these effects from the interface chemistry. The comparably low WF value for the up SAM is particularly important since it extends a rather limited variety of SAMs capable of lowering the WF of ITO.

The folding of DNA G-quadruplexes (G4) is essential to regulate expression of oncogenes and involves polymorphic long-lived intermediate states. G4 formation requires four G-tracts, but human gene-promoters often contain multiple Gtracts that act as spare-tires. These additional G-tracts are highly conserved and add multiple layers of functional complexity, as they are crucial to maintain G4 function after oxidative damage. Herein, we unravel the folding dynamics of the G4 sequence containing five G-tracts from cMYC, the major proliferation-driving oncogene. We devise a general method to induce folding at constant experimental conditions using a photochemical trapping strategy. Our data dissect the individual kinetics and thermodynamics of the spare-tire mechanism of cMYC-G4.

The kinetics of folding is crucial for the function of many regulatory RNAs including RNA G-quadruplexes. Here, we characterize the folding pathways of a G-quadruplex from the telomeric repeat-containing RNA by combining all-atom molecular dynamics and coarse-grained simulations with circular dichroism experiments. The quadruplex fold is stabilized by cations and thus, the ion atmosphere forming a double layer surrounding the highly charged quadruplex guides the folding process. To capture the ionic double layer in implicit solvent coarse-grained simulations correctly, we develop a matching procedure based on all-atom simulations in explicit water. The procedure yields quantitative agreement between simulations and experiments as judged by the populations of folded and unfolded states at different salt concentrations and temperatures. Subsequently, we show that coarse-grained simulations with a resolution of three interaction sites per nucleotide are well suited to resolve the folding pathways and their intermediate states. The results reveal that the folding progresses from unpaired chain via hairpin, triplex and double-hairpin constellations to the final folded structure. The two- and three-strand intermediates are stabilized by transient Hoogsteen interactions. Each pathway passes through two transient, on-pathway intermediates. Since these intermediates are degenerate with two to four alternative conformations per state, RNA quadruplex folding is a multi-pathway process with high conformational entropy.