Ihmels, Heiko
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Publication Access status: Metadata only , Fluorimetric Cell Analysis with 9‐Aryl‐Substituted Berberine Derivatives as DNA‐Targeting Fluorescent ProbesDNA‐sensitive fluorescent light‐up probes based on berberine are presented. This biogenic fluorophore was chosen as central unit to use its potential biocompatibility and its DNA‐binding properties. To provide predictable fluorescence quenching in aqueous solution and a fluorescence light‐up effect upon DNA binding, aryl substituents were attached at the 9‐position by Suzuki‐Miyaura coupling reactions. The 9‐arylberberine derivatives have a very low fluorescence quantum yield ( Φ fl =<0.02), which is caused by the radiationless deactivation of the excited state by torsional relaxation about the biaryl axis. In addition, these berberine derivatives intercalate into DNA with high affinity ( K b =2.0−22×10 4 M −1 ). Except for the nitrophenyl‐ and hydroxyphenyl‐substituted derivatives, all tested compounds exhibited a pronounced fluorescence light‐up effect upon association with DNA, because the deactivation of the excited‐state by torsional relaxation is suppressed in the DNA binding site. Most notably, it was shown exemplarily with the 9‐(4‐methoxyphenyl)‐ and the 9‐(6‐methoxynaphthyl)‐substituted derivatives that these properties are suited for fluorimetric cell analysis. In particular, these probes generated distinct staining patterns in eukaryotic cells (NIH 3T3 mouse fibroblasts), which enabled the identification of nuclear substructures, most likely heterochromatin or nucleoli, respectively.Source Type:Article2 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Metadata only , Photocontrolled Binding of Styrylnaphthyridine Ligands to Abasic Site‐Containing DNA by Reversible [2+2] Cycloaddition and Cycloreversion(2024); Five novel styrylnaphthyridine derivatives were synthesized and shown to operate as photoswitchable, selective ligands for abasic site‐containing DNA (AP‐DNA), which is an important therapeutic and diagnostic target. These compounds associate with AP‐DNA with binding constants of 0.5–8.4×10 4 M −1 as shown by photometric and fluorimetric titrations. Specifically, these ligands bind preferentially to AP‐DNA relative to regularly paired duplex DNA. As a special feature, the association of these ligands with DNA can be controlled by means of a reversible [2+2] photocycloaddition. Upon irradiation at 420 nm the photodimer is formed, which does not bind to AP‐DNA. In turn, the naphthyridine is regained with excitation at 315 nm. Most notably, this photoinduced deactivation and release of the DNA ligand can be performed in situ in the presence of AP‐DNA, thus providing a tool for on‐demand delivery of a DNA binder. Overall, these results provide a promising starting point for the development of functional AP‐DNA ligands whose bioactivity can be modulated by light with local and temporal control.Source Type:Article3 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Metadata only , Photoinduced [2+2] and [4+4] Cycloaddition and Cycloreversion Reactions for the Development of Photocontrollable DNA Binders(2024); In the current field of photopharmacology, molecular photoswitches are applied whose interactions with DNA can be triggered or controlled by light. And although several photochromic reactions have been shown to serve this purpose well, the reversible photocycloaddition and photocycloreversion reactions have been largely neglected. This absence of research is surprising because especially the photodimerization of a DNA ligand leads to products with significant change of the size and shape which, in turn, leads to strongly diminished or even suppressed DNA association. Therefore, photocycloaddition–cycloreversion sequences have a huge potential for the photoinduced, reversible deactivation and activation of ligand–DNA interactions, as will be shown with selected examples in this Concept Article . Specifically, heterostyryl and ‐stilbene derivatives are presented whose DNA–binding properties are efficiently switched in reversible [2+2] photocycloaddition reactions. In addition, the photocontrolled DNA–binding of anthracene derivatives and their heterocyclic benzo[ b ]quinolizinium analogues in a [4+4] photocycloaddition, as well as the use of this reaction as part of dual–mode switches in combination with redox‐active functionalities, are highlighted. Furthermore, examples of conjugates are provided, in which the photochromic unit is bound covalently to nucleic acids or proteins, such that the photocycloaddition reaction can be used for reversible photoinduced crosslinking, ligation, or inhibition of gene expression.Source Type:Article3 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Metadata only , Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[<i>c</i>]quinolizinium ionsThe photoreactions of selected styrylpyridine derivatives to the corresponding benzo[ c ]quinolizinium ions are described. It is shown that these reactions are more efficient in aqueous solution (97–44%) than in organic solvents (78–20% in MeCN). The quinolizinium derivatives bind to DNA by intercalation with binding constants of 6–11 × 10 4 M −1 , as shown by photometric and fluorimetric titrations as well as by CD- and LD-spectroscopic analyses. These ligand–DNA complexes can also be established in situ upon irradiation of the styrylpyridines and formation of the intercalator directly in the presence of DNA. In addition to the DNA-binding properties, the tested benzo[ c ]quinolizinium derivatives also operate as photosensitizers, which induce DNA damage at relative low concentrations and short irradiation times, even under anaerobic conditions. Investigations of the mechanism of the DNA damage revealed the involvement of intermediate hydroxyl radicals and C-centered radicals. Under aerobic conditions, singlet oxygen only contributes to marginal extent to the DNA damage.Source Type:Article4 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Metadata only , Photoinduced Reactions of Styrylpyridine Derivatives for the In Situ Formation of Selective Ligands for Apyrimidinic DNAThe photocyclization reaction of sterically demanding styrylpyridine derivatives was investigated and shown to depend on the type of substituent. With this method, a 2,2‐diphenyl‐1,3‐benzodioxolo‐annelated benzo[ c ]quinolizinium was synthesized, and its association with regular and abasic site‐containing DNA (AP‐DNA) was investigated by absorption, fluorescence, circular and linear dichroism spectroscopy. Specifically, this ligand binds preferentially to AP‐DNA relative to regular duplex DNA, and the AP‐DNA/ligand complex is formed in situ upon irradiation of the styrylpyridine substrate in the presence of the DNA.Source Type:Article2 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Metadata only , Spectroscopic Investigation of the Quadruplex DNA‐Binding Properties of 9‐Aryl‐Substituted Isoquinolinium DerivativesThe spectroscopic investigation of the binding properties of berberine‐type 9‐aryl‐substituted isoquinolinium derivatives with G‐quadruplex DNA (G4‐DNA) are presented. Photometric titrations show that these ligands bind with high affinity to the telomeric G4‐DNA form 22AG ( K =1.0–44×10 5 M −2 ). Furthermore, fluorimetric analysis of thermal DNA denaturation (FRET melting) reveals a significant thermal stabilization of G4‐DNA 22AG upon association with the methoxy‐substituted derivatives. As an analytically useful property, the derivatives with a phenyl substituent or with additional electron‐donating groups show a very weak fluorescence intensity, which increased significantly upon G4‐DNA complexation (fluorescence light‐up effect). Additional time‐resolved fluorescence spectroscopy indicated increased fluorescence lifetimes of the DNA‐bound 9‐(4‐methoxyphenyl)‐substituted derivative, when interacting with the quadruplex‐forming strand 22AG . Notably, the changes of the steady‐state and time‐resolved emission properties of the ligand are more pronounced with G4‐DNA than with duplex DNA so that the combination of these complementary methods may be used for the selective G4‐DNA detection.Source Type:Article2 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Metadata only , Switching between DNA binding modes with a photo- and redox-active DNA-targeting ligand(2023); The combination of a photochromic benzo[ b ]quinolizinium and a redox-active disulfide linker enables the control of DNA-binding properties by shifting between three different binding modes.Source Type:Article1 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Metadata only , Switching between DNA binding modes with a photo- and redox-active DNA-targeting ligand, part II: the influence of the substitution pattern(2023); A disulfide-functionalized photochromic system enables the control of DNA-binding properties by a combination of a photocycloaddition reaction, the redox reactions of the disulfide functionality, and an irreversible chemical degradation.Source Type:Article1 - Some of the metrics are blocked by yourconsent settings
Publication Access status: Metadata only , The N-biphenyldihydroisoquinolinium scaffold as a novel motif for selective fluorimetric detection of quadruplex DNA(2024); ; A cationic, donor–acceptor-substituted biphenyl derivative is presented as a quadruplex DNA-targeting fluorescent probe that enables the fluorimetric differentiation of quadruplex DNA forms.Source Type:Article2
