Thiolated nucleotides for immobilisation of DNA oligomers on gold surfaces.

Thiols have a strong tendency to be chemisorbed to gold surfaces forming self-assembled monolayers. 2] The feature of strong S Au bond formation has been exploited in numerous applications including the immobilisation of DNA on gold surfaces for the generation of DNA microarrays or gold electrodes for measuring charge migration mediated by double stranded DNA. To be immobilised on gold, DNA has to be modified with thiol functionalities. Usually, for this purpose oligonucleotides are equipped with thioalkyl moieties at the 5’or 3’-terminus. These modifications have been employed in studies dedicated to directly measure electrical transport through DNA molecules. 8] However, those transport measurements report contradictory results for the conduction behaviour of DNA. Some of these contradictions could be attributed to influences of the DNA sequence or the environment of the molecules. On the other hand, it is evident that poor overlap of the orbitals of the thiols with the p-system of the DNA as well as unreliable or unspecific bonding of the thiols to the metal electrodes are most likely playing a major role in causing these contradictions. Along these lines we became interested in the synthesis of oligonucleotides that bear short thioalkyl functions in close proximity to the p-system of the nucleobase to facilitate electrical transport through dsDNA. Herein we report the synthesis of new thiolated nucleotides, their incorporation in DNA oligonucleotides as well as studies employing fluorescence and atomic-force microscopy for verifying the immobilisation of the thiolated species onto gold substrates. For the design of the thiol modified nucleosides, future applications for transport measurements are kept in mind. The 5-position of thymidine was chosen for modification to be in close proximity to the p-system and to maintain accessibility over the major groove in double strand DNA, thus 1 shown in Scheme 1 bears a thiol-moiety directly attached to the nucleobase that is protected as ether. In another approach thymidine 2 is synthesised via the introduction of a thiophene moiety conjugated via an alkyne spacer to the nucleobase. To commence the synthesis of 1, the protected 5-iodo-2’-deoxyuridine 3 was first treated with NaH and after cooling to 78 8C with nBuLi and 1,2-bis(2-(trimethylsilyl)ethyl) disulfane