DNA with metal-mediated base pairs

DNA with metal-mediated base pairs

Metal-mediated base pairs represent a prominent means for the site-specific incorporation of metal-based functionality into nucleic acids. In metal-mediated base pairs, the metal ions are located inside the double helix. This unusual localization is accomplished by using artificial base surrogates capable of binding metal ions, hence by a formal substitution of hydrogen bonds within a base pair by coordinate bonds. We are designing artificial nucleobases to be used in is this kind of bio-inspired self-assembling array of metal ions. Moreover, we are developing applications for nucleic acids with metal-mediated base pairs.

Metal-Mediated Base Pairs: From Characterization to Application

B. Jash, J. Müller

Chem. Eur. J. 2017, 23,  17166–17178.

                                                                                                      DOI: 10.1002/chem.201703518

Contiguous Heterobimetallic Arrays of Metal-Mediated Base Pairs

N. Lefringhausen, C. Erbacher, M. Hebenbrock, U. Karst, J. Müller 

Inorg. Chem. 2026,  65, 17023–17029. 

DOI: 10.1021/acs.inorgchem.6c02244

Tuning the Duplex Stability of DNA Oligonucleotides Containing Metal-Mediated Base Pairs of Imidazole-Derived Nucleobases 

C. Bardehle, J. Müller 

Chem. Eur. J. 2025, 31, e202404332.  

DOI: 10.1002/chem.202404332

Metal-Modified Nucleic Acids: Metal-Mediated Base Pairs, Triples and Tetrads 

S. Naskar, R. Guha, J. Müller 

Angew. Chem. 2020, 59, 1397–1406. 

DOI: 10.1002/anie.201905913

DNA-templated nanoclusters

DNA-templated nanoclusters

In addition to our work on the site-specific functionalization of nucleic acids, we are developing DNA-stabilized silver nanoclusters (AgNC), representing a fascinating class of atomically precise nanoclusters. They have raised significant interest due to their biocompatibility and tunable emission wavelength ranging down to the near-infrared region, enabling potential applications in biosensing, bioimaging and therapeutics. We are particularly interested in using artificial nucleobases for the synthesis of AgNCs, thereby opening up new possibilities for tailoring their optical properties for those applications.

Fluorescent DNA-Templated Silver Nanoclusters from Silver(I)-Mediated Base Pairs 

J.C. Léon, D. González-Abradelo, C.A. Strassert, J. Müller 

Chem. Eur. J. 2018, 24, 8320–8324 

DOI: 10.1002/chem.201801858 

Lumos: Introducing luminescence into oligonucleotides

Lumos: Introducing luminescence into oligonucleotides

Transition metal complexes are promising candidates for various biological applications. However, these drugs and sensors often show limitations such as low solubility and significant side effects. In this context, nucleic acids have emerged as an interesting alternative. Therefore, the site-specific incorporation of transition metal ions is of high interest, as it can equip the DNA with metal-based properties, enabling a wide range of possible biomedical applications. Our work varies from developing lanthanoid-mediated luminescent base pairs to the design of platinum(II)-modified DNA, with applications ranging from molecular sensing to bioimaging. This research is complemented by interdisciplinary collaborations with the  European Institute for Molecular Imaging (EIMI) and the Ruhr Universität Bochum (RUB), thereby facilitating the transition towards biomedical potential.

Site-specific covalent metalation of DNA oligonucleotides with phosphorescent platinum(II) complexes 

F. Boisten, I. Maisuls, T. Schäfer, C.A. Strassert, J. Müller 

Chem. Sci. 2023, 14, 2399–2403. 

DOI: 10.1039/d2sc05916a

Lumos: A β-Diketone-Derived Artificial Nucleobase Forming Inter-Strand Complexes in DNA that Promote Lanthanoid Ion Luminescence 

C. Bardehle, M. Hebenbrock, A. Hepp, J. Müller 

ChemistryEurope 2025, 3, e202400116. 

DOI: 10.1002/ceur.202400116 

Covalent Attachment of a Platinum(II) Complex inside DNA Duplexes

T. Schäfer, I. Maisuls, F. Boisten, M. Hebenbrock, A. Hepp, C.A. Strassert, J. Müller 

ChemistryEurope 2026, 4, e202500416. 

DOI: 10.1002/ceur.202500416

Covalently Platinated DNA Oligonucleotides as Ratiometric Dioxygen Sensors 

T. Schäfer, N. Bauer, I. Maisuls, M. Layh, A. Hepp, C.A. Strassert, F. Kiefer, J. Müller 

Bioconj. Chem. 2025, 36, 2487–2496. 

DOI: 10.1021/acs.bioconjchem.5c00449 

Higher-order DNA structures

Higher-order DNA structures 

Beyond the well-known double helical B-DNA structure, DNA can adopt a wide range of triplex and quadruplex structures such as guanine quadruplex DNA and i-motifs. We are therefore developing metal complexes capable of selectively recognizing and targeting these non-canonical DNA structures, with the aim of establishing novel metallo-drugs that operate through previously unexplored mechanisms of action.

Are i-Motif Structures in DNA Compatible with Cytosine–Ag(I)–Cytosine Base Pairs?

V. Seiffert,  C. López-Chamorro, M. Barceló-Oliver, C. Erbacher, U. Karst, Dr. M. Hebenbrock, H.B. Kraatz, M.A. Galindo, J. Müller 

Angew. Chem. 2026, 65, e19809. 

DOI: 10.1002/anie.202519809

Water-soluble luminescent platinum(II) complexes for guanine quadruplex binding 

S. Kroos, M. Hebenbrock, A. Hepp, M. Layh, J. Lüke, A.R. Tonkul, C.A. Strassert, J. Müller

Dalton Trans. 2025, 54, 5367–5390.

DOI: 10.1039/d4dt03067b

Targeting Guanine Quadruplexes with Luminescent Platinum(II) Complexes Bearing a Pendant Nucleobase 

R. Guha, D. Defayay, A. Hepp, J. Müller 

ChemPlusChem 2021, 86, 662–673.

DOI: 10.1002/cplu.202100135

Platinum(II) and palladium(II) complexes of tridentate hydrazone-based ligands as selective guanine quadruplex binders 

A. Schmidt, R. Guha, A. Hepp, J. Müller 

J. Inorg. Biochem. 2017, 86, 58–66. 

DOI: 10.1016/j.jinorgbio.2017.07.003