## 6 Serinol Nucleic Acids (SNA)
The above-mentioned strong stabilization of D:U or D:T base pairs may lead to an undesirable situation in which strong hydrogen bonds promote the formation of intra-molecular double-stranded structures within an SNA probe, thereby interfering with hybridization with the target RNA. To avoid undesirable self-hybridization, SNA nucleotides carrying 2-thiothymine (T\({}^{\text{S}}\)) or 2-thiouracil (U\({}^{\text{S}}\)) instead of thymine or uracil have been developed [71]. The sulfur atom (which has a much larger atomic radius than an oxygen atom) at the C2 position causes a steric hindrance that prevents intramolecular pairing with the amino group at position 2 in 2,6-diaminopurine. On the other hand, the D residue in SNA interacts with T and U in a complementary DNA or RNA strand, respectively, and sulfur-substituted SNA-T\({}^{\text{S}}\) and SNA-U\({}^{\text{S}}\) normally hybridize with A in the target oligomer. An interesting way to control the strength of SNA/RNA hybridization is based on the photochemically induced [2 + 2] cycloaddition of two 8-pyrenylvinyl adenine residues (**37**, Scheme 8) present in adjacent positions to each other in an SNA strand [72]. Such a modified adenine exerts the canonical Watson-Crick base-pairing with thymine or uracil. A model SNA oligomer of sequence GCTA*A*TGC, where the letter A* stands for 8-pyrenylvinyl-adenine, and an RNA oligomer 5\({}^{\prime}\)-AAGCAUUAGCAA-3 complementary across the underlined segment, form a duplex with Tm = 35 \({}^{\circ}\)C. After irradiation with 455 nm light at 20 \({}^{\circ}\)C for 1 h, almost complete crosslinking was noted and no melting transition was observed, proving that the duplex was dissociated. The authors claim that the local structure around the crosslinked A*=A* was disturbed to the extent that the dissociation of the duplex was forced. Upon irradiation with 340 nm light, 90% of the crosslinking was reversed within 15 min, and a sigmoidal melting curve was recorded. Importantly, three successive crosslinking/recovery processes were possible by alternating irradiation with 455 and 340 nm light without significant photobleaching. Similar functionality was achieved with 8-naphthylvinyl-adenine (A\({}^{\text{N}}\), **38**, Chart 12), although in this case crosslinking to form the A\({}^{\text{N}}\)=A\({}^{\text{N}}\) adduct was performed with light of 340-405 nm (455 nm for A*=A*) and the restoration of A\({}^{\text{N}}\) occurred upon irradiation with \(\leq\)300 nm light (340 nm for A*) [73]. For a system A*, A\({}^{\text{N}}\) crosslinking to A*=A\({}^{\text{N}}\) was performed with light from 405 to 465 nm and recovery occurred upon irradiation with \(\leq\)340 nm. Since certain wavelength ranges for (A*,A\({}^{\text{N}}\)) and (A\({}^{\text{N}}\),A\({}^{\text{N}}\)) do not overlap, it was possible to selectively generate four possible hybridization states using a mixture of SNA-(A*,A\({}^{\text{N}}\)) and SNA-(A\({}^{\text{N}}\),A\({}^{\text{N}}\)). A suitable combination of wavelengths is: 340-405 nm to form A\({}^{\text{N}}\)=A\({}^{\text{N}}\), 405-465 nm to form A*=A\({}^{\text{N}}\), \(\leq\)300 nm to recover (A\({}^{\text{N}}\),A\({}^{\text{N}}\)) and \(\leq\)340 nm to recover (A*,A\({}^{\text{N}}\)). The authors also found that SNA-(A*,A*) cannot be used in this double-switch because a simultaneous cyclo-reversion of A*=A* and A\({}^{\text{N}}\)=A\({}^{\text{N}}\) would be impossible due to the poor absorption of 300 nm light by the A*=A* photo-adduct. SNA constructs are also used as analytical tools in biology and biochemistry. In a similar approach to the DNA probe using aTNA-perylene units [66], a fluorescent 5-(perylenylethylynyl)uracil unit (\({}^{\text{Pe}}\)U) was incorporated into SNA molecules as a substitute for thymine [74]. In the single-stranded state, interactions between the perylenes resulted in self-quenching of the fluorophores.