{
  "abstract": "Thionucleobases provide distinctive hydrogen-bonding, electronic, and photochemical properties, but their site-specific incorporation into DNA often requires specialized sulfurcontaining phosphoramidites and multistep monomer synthesis. Here, we establish a unified protocol using sodium hydrosulfide (NaSH) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) for direct on-support conversion of 8-bromo-2′-deoxyadenosine (Br 8 dA) to 8-thio-2′deoxyadenosine (s 8 dA), late-stage C8 thioether diversification, and concurrent conversion of Br 8 dA and 4-triazolylthymidine within a single DNA strand. Electrophilic precursor nucleosides were incorporated by standard solid-phase synthesis and subsequently converted while the oligonucleotide remained support-bound. Conversion of Br 8 dA to s 8 dA was first demonstrated using 2-(trimethylsilyl)ethanethiol and subsequently achieved directly with NaSH·xH2O, eliminating the need for a separate fluoride-mediated deprotection step. Substitution at the C8 was compatible with mixed sequences, multiple modifications, and a range of aliphatic and aromatic thiols, enabling late-stage installation of diverse sulfurcontaining functionalities. Application of the same support-bound protocol to 4-triazolylthymidine afforded DNA containing one or more 4-thiothymidine (s 4 T) residues, and both thionucleobases could be generated within the same strand. Products were characterized by strong-anion-exchange high-performance liquid chromatography and electrospray ionization mass spectrometry. This workflow shifts sulfur installation from specialized monomer synthesis to a simple late-stage conversion and provides practical access to site-specifically thiolated and C8-thioether-functionalized DNA.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, University of Guelph, 50 Stone Rd E, Guelph, ON, N1G 2W1"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jagandeep S. Saraya",
      "orcid": "0009-0008-0245-1899"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicholas G. Horton",
      "orcid": "0009-0006-6924-9551"
    },
    {
      "affs": [
        0
      ],
      "name": "Derek K. O'Flaherty",
      "orcid": "0000-0003-3693-6380"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bmbg8sa98713d.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008295/v1",
  "fulltext_url": null,
  "id": "bmbg8sa98713d",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008295/v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|DNA and Nucleic Acid Chemistry"
    ]
  ],
  "openalex": "W7208754490",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008295/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-04",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/bmbg8sa98713d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.26434/chemrxiv.15008295",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008295/v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA and Nucleic Acid Chemistry",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A Solid-Phase Platform for Site-Specific Thiolation and Thioether Functionalization of DNA Oligonucleotides",
  "title_text": "A Solid-Phase Platform for Site-Specific Thiolation and Thioether Functionalization of DNA Oligonucleotides",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/bmbg8sa98713d",
  "venue": "ChemRxiv",
  "versions": []
}