A Tutorial on Automated Mass Spectral Analysis Using NucleoSpec for Compositional Assignment of Nucleic Acid-Silver Complexes and Nanoclusters.
4 affiliations
- 1Department of Materials Science and Engineering, University of California, Irvine, California 92697, United States.
- 2Department of Chemistry, University of California, Irvine, California 92697, United States.
- 3Department of Chemical and Biomolecular Engineering, University of California, Irvine, California 92697, United States.
- 4Department of Physics and Astronomy, University of California, Irvine, California 92697, United States.
Abstract
Nucleic acid-metal complexes, such as DNA-stabilized silver nanoclusters (DNA-Ag N ) and Ag-(I)-mediated DNA duplexes, show promise for applications ranging from biomedical imaging to bioelectronics and sensing. Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool for precisely resolving their compositions, but the data analysis procedure can be challenging and time-consuming. No general-purpose software can automatically assign compositions of nucleic acid-silver complexes, most notably for DNA-Ag N , whose masses depend on the oxidation state of the silver core. We address these challenges by developing an automated data analysis workflow for ESI-MS of nucleic acid-silver complexes. This tutorial presents the analysis workflow and introduces NucleoSpec, an open-source, web-based platform that consolidates charge state determination, constraint-based composition enumeration, isotope-pattern matching, and adduct/conjugate handling into a single browser-accessible interface. The platform is benchmarked on published molecular formulas determined by manual analysis for DNA-Ag N , xeno-nucleic acid stabilized Ag N (XNA-Ag N ), nucleic acid-Ag-(I) complexes, and chemically modified DNA-Ag N , reproducing assignments to single-proton precision (median centroid offset of 0.03 m/z) for spectra of adequate signal-to-noise. Low-signal peaks for which adjacent valence electron counts become difficult to distinguish are flagged by NucleoSpec for user inspection. By lowering the barrier to high-resolution compositional analysis and supporting integration into high-throughput pipelines, NucleoSpec addresses a key experimental bottleneck in informatics-guided design of nucleic acid-metal complexes.
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BibTeX
@article{lin2026tutorial,
title = {{A Tutorial on Automated Mass Spectral Analysis Using NucleoSpec for Compositional Assignment of Nucleic Acid-Silver Complexes and Nanoclusters.}},
author = {I-Hsin Lin and Stacy M Copp},
journal = {ACS measurement science au},
year = {2026},
month = aug,
doi = {10.1021/acsmeasuresciau.6c00178},
url = {https://europepmc.org/article/MED/42921423},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A Tutorial on Automated Mass Spectral Analysis Using NucleoSpec for Compositional Assignment of Nucleic Acid-Silver Complexes and Nanoclusters.
AU - I-Hsin Lin
AU - Stacy M Copp
PY - 2026
DA - 2026/08/15
JO - ACS measurement science au
DO - 10.1021/acsmeasuresciau.6c00178
UR - https://europepmc.org/article/MED/42921423
AB - Nucleic acid-metal complexes, such as DNA-stabilized silver nanoclusters (DNA-Ag N ) and Ag-(I)-mediated DNA duplexes, show promise for applications ranging from biomedical imaging to bioelectronics and sensing. Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool for precisely resolving their compositions, but the data analysis procedure can be challenging and time-consuming. No general-purpose software can automatically assign compositions of nucleic acid-silver complexes, most notably for DNA-Ag N , whose masses depend on the oxidation state of the silver core. We address these challenges by developing an automated data analysis workflow for ESI-MS of nucleic acid-silver complexes. This tutorial presents the analysis workflow and introduces NucleoSpec, an open-source, web-based platform that consolidates charge state determination, constraint-based composition enumeration, isotope-pattern matching, and adduct/conjugate handling into a single browser-accessible interface. The platform is benchmarked on published molecular formulas determined by manual analysis for DNA-Ag N , xeno-nucleic acid stabilized Ag N (XNA-Ag N ), nucleic acid-Ag-(I) complexes, and chemically modified DNA-Ag N , reproducing assignments to single-proton precision (median centroid offset of 0.03 m/z) for spectra of adequate signal-to-noise. Low-signal peaks for which adjacent valence electron counts become difficult to distinguish are flagged by NucleoSpec for user inspection. By lowering the barrier to high-resolution compositional analysis and supporting integration into high-throughput pipelines, NucleoSpec addresses a key experimental bottleneck in informatics-guided design of nucleic acid-metal complexes.
SN - 2694-250X
ER -