Binding properties of pyrene-porphyrin dyad to G-quadruplexes in the presence of K+ and Na+ ion and their effect on stability

Discriminating between Parallel, Anti-Parallel and Hybrid G-Quadruplexes: Mechanistic Details on Their Binding to Small Molecules

“…As for similar systems, a pyrene derivative of TMPyP4 (Figure 3b) was shown to bind (and destabilise) similarly parallel and antiparallel G4s, but the latter was chair-type; these authors evidenced the importance of the length (number of T residues) in the lateral loop to modulate the binding [49]. Theoretical studies on antraquinone derivatives (Figure 3c) bearing also methyl imidazole or methyl pyrene have produced information on the details of the binding, which drive the preference to bind parallel or mixed hybrid structures compared to the antiparallel structure [50]; besides other thermodynamic details, this work enlightens the role played by "tail" substituents, which produce an additional effect to the sitting-atop stacking of the porphyrin core in loop binding.…”

“…Figure 3. Molecular structures of the selective G4 binders of the porphyrin family reviewed here; (a)[42][43][44][45][46]48], (b)[49], (c)[50], (d)[51], (e)[52], (f)[53] and (g)[54]. In this and similar figures, red letters evidence parallel G4s high selectivity, blue letters correspond to molecules selective for antiparallel topology (absent here), and the systems with other/mixed behaviour have black lettering.…”

“…Additionally, it was found that TMPyP4 unselectively binds to a thrombin-binding aptamer forming parallel and anti-parallel basket-type G4s but with a binding mode outside of the quadruplexes and based only on weak electrostatic interactions with the phosphates [48]. (a) [42][43][44][45][46]48], (b) [49], (c) [50], (d) [51], (e) [52], (f) [53] and (g) [54]. In this and similar figures, red letters evidence parallel G4s high selectivity, blue letters correspond to molecules selective for antiparallel topology (absent here), and the systems with other/mixed behaviour have black lettering.…”

“…The results are discussed also in light of the importance of the orientation of the ring oxygen atoms from the guanine deoxyribose moieties to the G4 plane for the stacking of π-conjugated macrocycles such as heme; conversely, the binding is not largely affected by the negative electrostatic potential due to nearly phosphate groups. In the absence of the iron metal centre (turning heme to protoporphyrin IX, PPIX, Figure 3e), the selectivity is maintained: PPIX binds parallel G4s 100-fold better than antiparallel ones so that PPIX can even be used as a sensitive turn-on sensor for parallel G4s [49], (c) [50], (d) [51], (e) [52], (f) [53] and (g) [54]. In this and similar figures, red letters evidence parallel G4s high selectivity, blue letters correspond to molecules selective for antiparallel topology (absent here), and the systems with other/mixed behaviour have black lettering.…”