2,6-diaminopurine and 2-thiouridine . In particular, 2,6-diaminopurine can interact with canonical uridine (or its C5-(1-propynyl) derivative) by forming a third hydrogen bond in the Watson-Crick base pairing pattern which could result in stronger binding and increased self-replication rate . Similarly, greater thermodynamic stability of the 2-thiouracil:adenine base pair (Fig. ) and g)) was suggested as the reason for improved kinetics and fidelity of nonenzymatic RNA template copying with 2-thiouridine monomers being present both in the templating strand as well as among the activated monomers . More recently, Kim and co-workers demonstrated that highly efficient nonenzymatic RNA template copying could be achieved with activated inosine monomers (Fig. f), while activated 8oxopurine nucleotides proved to perform poorly under the same conditions. It is worth emphasizing that as opposed to the G:C Watson-Crick base pair, inosine interacts with cytosine through only two hydrogen bonds and not three. Therefore, the observed comparable performance of inosine and guanosine monomers challenges the assumption that nonenzymatic RNA template copying is largely regulated by the thermodynamic stability of specific base pairs and the molecular mechanism of the process is more complex.