Organometallic modification confers oligonucleotides new functionalities.

To improve their properties or to introduce entirely new functionalities, the intriguing scaffolds of nucleic acids have been decorated with various modifications, most recently also organometallic ones. While challenging to introduce, organometallic modifications offer the potential of expanding the field of application of metal-dependent functionalities to metal-deficient conditions, notably those of biological media. So far, organometallic moieties have been utilized as probes, labels and catalysts. This Feature Article summarizes recent efforts and predicts likely future developments in each of these lines of research.

Organomercury oligonucleotide conjugates as artificial ribonucleases.

Two oligonucleotide conjugates sharing the same sequence but incorporating a different 5'-terminal organometallic moiety were synthesized, by either direct mercuration in solution or oximation with an organomercury aldehyde on solid support. The potential of these conjugates to serve as new type of artificial ribonucleases was tested with a complementary 2´-O-methyl-RNA target sequence featuring a single cleavable RNA phosphodiester linkage. Both organomercury oligonucleotides greatly outperformed their metal-free counterparts as well as the previously reported small molecule organomercury RNA cleaving agent in catalytic activity, providing an important proof-of-concept. Compared to state-of-the-art metal-dependent artificial ribonucleases, however, the observed activity was modest.

Cleavage of an RNA Model Compound by an Arylmercury Complex.

A water-soluble arylmercury complex has been synthesized, and its ability to catalyze the cleavage of the phosphodiester linkage of the RNA model compound adenylyl-3',5'-(2',3'-O-methyleneadenosine) has been assessed over a pH range of 3-8.5 and a catalyst concentration range of 0-7 mM. In the presence of 1 mM catalyst, the observed pH-rate profile featured a new pH-independent region between pH 6 and 7, the catalyzed reaction being as much as eight times faster than the background reaction. At pH 7, the acceleration increased linearly from three- to 17-fold upon increasing the catalyst concentration from 1 to 7 mM. The linear dependence indicates a relatively low affinity of the catalyst for the substrate and, hence, the potential for considerable improvement on tethering to an appropriate targeting group, such as an oligonucleotide.