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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.

The non-fluorescent 9-nitrobenzo[b]quinolizinium is readily reduced by nitroreductase to a fluorescent reaction product. The resulting light-up effect enables the selective detection of nitro-reductase activity in vitro and in Escherichia coli bacterial cultures.

The 9‐ and 12‐dimethylaminophenyl‐substituted berberine derivatives 3 a and 3 b were readily synthesized by Suzuki‐Miyaura reactions and shown to be useful fluorescent probes for the optical detection of quadruplex DNA (G4‐DNA). Their association with the nucleic acids was investigated by spectrometric titrations, CD and LD spectroscopy, and with DNA‐melting analysis. Both ligands bind to duplex DNA by intercalation and to G4‐DNA by terminal π stacking. At neutral conditions, they bind with higher affinity (K b=105−106 M−1) to representative quadruplex forming oligonucleotides 22AG, c‐myc, c‐kit, and a2, than to duplex calf thymus (ct) DNA (K b=5‐7×104 M−1). At pH 5, however, the affinity of 3 a towards G4‐DNA 22AG is higher (K b=1.2×106 M−1), whereas the binding constant towards ct DNA is lower (K b=3.9×103 M−1) than under neutral conditions. Notably, the association of the ligand with DNA results in characteristic changes of the absorption and emission properties under specific conditions, which may be used for optical DNA detection. Other than the parent berberine, the ligands do not show a noticeable increase of their very low intrinsic emission intensity upon association with DNA at neutral conditions. In contrast, a fluorescence light‐up effect was observed upon association to duplex (Φ fl=0.01) and quadruplex DNA (Φ fl=0.04) at pH 5. This fluorimetric response to G4‐DNA association in combination with the distinct, red‐shifted absorption under these conditions provides a simple and conclusive optical detection of G4‐DNA at lower pH., The very weak fluorescence of 4‐dimethylaminophenyl‐substituted berberines only increases significantly if both their conformational flexibility is strongly restricted, i. e. in viscous medium or when bound to quadruplex DNA, and the amino group is protonated at low pH. This requirement of a dual stimulation to cause a light‐up effect enables the spectrometric detection of quadruplex DNA at pH 5.

The suitability of 3-hydroxy-4-pyridylisoquinoline to operate as fluorescent chemosensor for the detection of metal ions was investigated. For that purpose, the interactions of the title compound with selected metal ions were investigated by absorption and emission spectroscopy. The complexation of Zn2+, Fe2+, Mg2+ with 1:1 and 2:1 stoichiometry leads to characteristic optical responses that depend significantly on the employed solvents, thus allowing for the fluorimetric identification and detection of particular metal cations in a matrix-based pattern analysis or by fluorimetric titrations. Graphical abstract

A novel type of azoniahetarene, namely, benzo[

The photochromic norbornadiene/quadricyclane system is among the most promising candidates for molecular solar thermal (MOST) energy storage. As in this context there is still the need for new tailor-made derivatives, borylated norbornadienes were synthesized that may be used as versatile building blocks. Thus, the 4,4,5,5-tetramethyl-2-(bicyclo[2.2.1]heptadien-2-yl)-1,3,2-dioxaborolane was prepared and shown to be a suitable substrate for Pd-catalyzed Suzuki–Miyaura coupling reactions with selected haloarenes. It was demonstrated exemplarily that the novel monosubstituted 2-(1-naphthyl)norbornadiene, that is accessible through this route, is transformed to the corresponding quadricyclane upon irradiation, whereas the back reaction can be accomplished by thermal treatment.

Abstract: Apurinic and apyrimidinic sites, also referred to as abasic or AP sites, are residues of duplex DNA in which one DNA base is removed from a Watson-Crick base pair. They are formed during the enzymatic repair of DNA and offer binding sites for a variety of guest molecules. Specif-ically, the AP site may bind an appropriate ligand as a substitute for the missing nucleic base, thus stabilizing the abasic site-containing DNA (AP-DNA). Notably, ligands that bind selectively to abasic sites may be employed for analytical and therapeutical purposes. As a result, there is a search for structural features that establish a strong and selective association of a given ligand with the abasic position in DNA. Against this background, this review provides an overview of the different classes of ligands for abasic site-containing DNA (AP-DNA). This review covers covalently binding sub-strates, namely amine and oxyamine derivatives, as well as ligands that bind to AP-DNA by non-covalent association, as represented by small heterocyclic aromatic compounds, metal-organic com-plexes, macrocyclic cyclophanes, and intercalator-nucleobase conjugates. As the systematic devel-opment of fluorescent probes for AP-DNA has been somewhat neglected so far, this review article contains a survey of the available reports on the fluorimetric response of the ligand upon binding to the AP-DNA. Based on these data, this compilation shall present a perspective for future develop-ments of fluorescent probes for AP-DNA.

The reaction of sodium cyanate with benzo[ b]quinolizinium substrates at room temperature gave 3-hydroxy-4-pyridyl-isoquinoline derivatives in good yields. Presumably, the overall reaction proceeds through an ANRORC-type sequence, that is, addition of the nucleophile, ring opening, and ring closure. Preliminary photophysical investigation of the parent compound revealed a pronounced sensitivity of its emission properties toward solvent effects and the pH of the medium.

Indolizine derivatives are obtained by irradiation of 2-benzoyl-N-benzylpyridinium derivatives and dimethyl acetylene dicarboxylate, thus providing a competitive and complementary base- and catalyst-free synthesis. With this method, the first example of a crystallochromic indolizine is presented, whose color in the solid state depends on the out-of-plane torsion of the benzoyl substituent.

The known azastilbene (E)-1,2-di(quinolin-3-yl)ethane (2a) and the novel azoniastilbene derivatives (E)-2-(2-(naphthalen-2-yl)vinyl)quinolizinium (2b) and (E)-3,3′-(ethane-1,2-diyl)bis(1-methylquinolinin-1-ium) (2c) were synthesized. Their interactions with duplex and quadruplex DNA (G4-DNA) were studied by photometric, fluorimetric, polarimetric and flow-LD analysis, and by thermal DNA denaturation studies, as well as by 1H-NMR spectroscopy. The main goal of this study was a comparison of these conformationally flexible compounds with the known G4-DNA-binding diazoniadibenzo[b,k]chrysenes, that have a comparable π-system extent, but a rigid structure. We have observed that the aza- and azoniastilbene derivatives 2a–c, i.e. compounds with almost the same spatial dimensions and steric demand, bind to DNA with an affinity and selectivity that depends significantly on the number of positive charges. Whereas the charge neutral derivative 2a binds unspecifically to the DNA backbone of duplex DNA, the ionic compounds 2b and 2c are typical DNA intercalators. Notably, the bis-quinolinium derivative 2c binds to G4-DNA with moderate affinity (Kb = 4.8 × 105 M−1) and also stabilizes the G4-DNA towards thermal denaturation (ΔTm = 11 °C at ligand–DNA ratio = 5.0). Strikingly, the corresponding rigid counterpart, 4a,12a-diazonia-8,16-dimethyldibenzo[b,k]chrysene, stabilizes the G4-DNA to an even greater extent under identical conditions (ΔTm = 27 °C). These results indicate that the increased flexibility of a G4-DNA ligand does not necessarily lead to stronger interactions with the G4-DNA as compared with rigid ligands that have essentially the same size and π system extent.

There is an ongoing interest in 1 O2 sensitizers, whose activity is selectively controlled by their interaction with DNA. To this end, we synthesized three isomeric pyridinium alkynylanthracenes 2 o-p and a water-soluble trapping reagent for 1 O2 . In water and in the absence of DNA, these dyes show a poor efficiency to sensitize the photooxygenation of the trapping reagent as they decompose due to electron transfer processes. In contrast, in the presence of DNA 1 O2 is generated from the excited DNA-bound ligand. The interactions of 2 o-p with DNA were investigated by thermal DNA melting studies, UV/vis and fluorescence spectroscopy, and linear and circular dichroism spectroscopy. Our studies revealed an intercalative binding with an orientation of the long pyridyl-alkynyl axis parallel to the main axis of the DNA base pairs. In the presence of poly(dA : dT), all three isomers show an enhanced formation of singlet oxygen, as indicated by the reaction of the latter with the trapping reagent. With green light irradiation of isomer 2 o in poly(dA : dT), the conversion rate of the trapping reagent is enhanced by a factor >10. The formation of 1 O2 was confirmed by control experiments under anaerobic conditions, in deuterated solvents, or by addition of 1 O2 quenchers. When bound to poly(dG : dC), the opposite effect was observed only for isomers 2 o and 2 m, namely the trapping reagent reacted significantly slower. Overall, we showed that pyridinium alkynylanthracenes are very useful intercalators, that exhibit an enhanced photochemical 1 O2 generation in the DNA-bound state.

A phosphate-substituted, zwitterionic berberine derivative was synthesized and its binding properties with duplex DNA and G4-DNA were studied using photometric, fluorimetric and polarimetric titrations and thermal DNA denaturation experiments. The ligand binds with high affinity toward both DNA forms (Kb = 2–7 × 105 M−1) and induces a slight stabilization of G4-DNA toward thermally induced unfolding, mostly pronounced for the telomeric quadruplex 22AG. The ligand likely binds by aggregation and intercalation with ct DNA and by terminal stacking with G4-DNA. Thus, this compound represents one of the rare examples of phosphate-substituted DNA binders. In an aqueous solution, the title compound has a very weak fluorescence intensity (Φfl &lt, 0.01) that increases significantly upon binding to G4-DNA (Φfl = 0.01). In contrast, the association with duplex DNA was not accompanied by such a strong fluorescence light-up effect (Φfl &lt, 0.01). These different fluorimetric responses upon binding to particular DNA forms are proposed to be caused by the different binding modes and may be used for the selective fluorimetric detection of G4-DNA.

Eleven novel 10-O-aryl-substituted berberrubine and berberine derivatives were synthesized by the Cu2+-catalyzed Chan–Evans–Lam coupling of berberrubine with arylboronic acids and subsequent 9-O-methylation. The reaction is likely introduced by the Cu2+-induced demethylation of berberrubine and subsequent arylation of the resulting 10-oxyanion functionality. Thus, this synthetic route represents the first successful Cu-mediated coupling reaction of berberine substrates. The DNA-binding properties of the 10-O-arylberberine derivatives with duplex and quadruplex DNA were studied by thermal DNA denaturation experiments, spectrometric titrations as well as CD and LD spectroscopy. Fluorimetric DNA melting analysis with different types of quadruplex DNA revealed a moderate stabilization of the telomeric quadruplex-forming oligonucleotide sequence G3(TTAG3)3. The derivatives showed a moderate affinity towards quadruplex DNA (Kb = 5–9 × 105 M−1) and ct DNA (Kb = 3–5 × 104 M−1) and exhibited a fluorescence light-up effect upon complexation to both DNA forms, with slightly higher intensity in the presence of the quadruplex DNA. Furthermore, the CD- and LD-spectroscopic studies revealed that the title compounds intercalate into ct DNA and bind to G4-DNA by terminal stacking.

A series of ten 2,7- and 2,8-diarylquinolizinium derivatives was synthesized and their DNA-binding and cytotoxic properties were investigated. Except for one nitro-substituted derivative all tested diarylquinolizinium ions bind to DNA with sufficient affinity (2 × 104 M−1–2 × 105 M−1). It was shown with photometric, fluorimetric and polarimetric titrations as well as with flow-LD analysis that the ligands bind mainly by intercalation to duplex DNA, however, depending on the ligand–DNA ratio, groove binding and backbone association were also observed with some derivatives. The biological activity was further investigated with tests of cytotoxicity and antiproliferative properties towards non-tumor cells and selected cancer cells, along with cell cycle analysis and an annexin-V assay. Notably, substrates that carry donor-functionalities in the 4-position of the phenyl substituents revealed a strong, and in some cases selective, antiproliferative activity as quantified by the growth inhibition, GI50, at very low micromolar and even submicromolar level both in leukemia and solid tumors.

A small series of five novel berberine derivatives was synthesized by the Cu-catalyzed click reaction of 9-propargyladenine with 9-O-(azidoalkyl)berberine derivatives. The association of the resulting berberine–adenine conjugates with representative quadruplex-forming oligonucleotides 22AG dA(G3TTA)3G3 and a2 d(ACAG4TGTG4)2 was examined with photometric and fluorimetric titrations, thermal DNA denaturation analysis, and CD spectroscopy. The results from the spectrometric titrations indicated the formation of 2:1 or 1:1 complexes (ligand:G4-DNA) with log Kb values of 10–11 (2:1) and 5–6 (1:1), which are typical for berberine derivatives. Notably, a clear relationship between the binding affinity of the ligands with the length of the alkyl linker chain, n, was not observed. However, depending on the structure, the ligands exhibited different effects when bound to the G4-DNA, such as fluorescent light-up effects and formation of ICD bands, which are mostly pronounced with a linker length of n = 4 (with a2) and n = 5 (with 22AG), thus indicating that each ligand–G4-DNA complex has a specific structure with respect to relative alignment and conformational flexibility of the ligand in the binding site. It was shown exemplarily with one representative ligand from the series that such berberine–adenine conjugates exhibit a selective binding, specifically a selectivity to quadruplex DNA in competition with duplex DNA, and a preferential thermal stabilization of the G4-DNA forms 22AG and KRAS. Notably, the experimental data do not provide evidence for a significant effect of the adenine unit on the binding affinity of the ligands, for example, by additional association with the loops, presumably because the adenine residue is sterically shielded by the neighboring triazole unit.

Quadruplex DNA, which is a relevant target for anticancer therapies, may alter its conformation because of interactions with interfaces. In pursuit of a versatile methodology to probe adsorption-induced conformational changes, the interaction between a fluorescent [2.2.2]heptamethinecyanine dye and quadruplex DNA (G4-DNA) was studied in solution and on surfaces. In solution, the cyanine dye exhibits a strong light-up effect upon the association with G4-DNA without interference from double-stranded DNA. In addition, a terminal π-stacking as a binding mode between the cyanine dye and G4-DNA is concluded using NMR spectroscopy. To unravel the effects of adsorption on the conformation of quadruplex-DNA, G4-DNA, and double-stranded and single-stranded DNA were adsorbed to positively charged poly(allylamine) hydrochloride (PAH) surfaces, both in planar and in constrained 55 nm diameter aluminum oxide nanopore formats. All DNA forms showed a very strong affinity to the PAH surfaces as shown by surface plasmon resonance and reflectometric interference spectroscopy. The significant increase of the fluorescence emission intensity of the cyanine light-up probe observed exclusively for surface immobilized G4-DNA affords evidence for the adsorption of G4-DNA on PAH with retained quadruplex conformation.

The association of organic ligands with nucleic acids is an important event in biology and in medicine because it may affect the regular function of the DNA. In this context, quadruplex DNA (G4-DNA) has gained special attention as a promising drug target. In this contribution, the complex formation between the tetracationic tetraazoniapentapheno[6,7-h]pentaphene and the oligonucleotide Tel26 [d(A3G3T2AG3T2AG3T2AG3A2)], which forms a (3+1) antiparallel/parallel structure (hybrid-1), was investigated by 1H-NMR spectroscopy. The analysis of the different developments of shifts and line broadening of the imino proton signals of the guanine residues revealed a preferential terminal π stacking of the ligand. Considering accessibility and steric constraints of the possible binding sites it is proposed that the ligand may stack on top of the A3–A9–A21 triplet at one terminal end of the quadruplex, rather than on a G4-quartet.

Direct photolysis and quenching experiments with styrene oxide support the existence of an efficient triplet photochemical pathway to benzyl radical formation. Similar photolytic behavior for styrene glycol carbonate strongly supports the 1,3-diradical, resulting from the scission of the benzylic C-O bond, as the geometric source of the triplet pathway. Primary photoproducts were determined by both NMR and HPLC analysis and we observed that toluene and bibenzyl were both primary photoproducts, not secondary photoproducts.

Six new 8-styryl-substituted coralyne derivatives 4a–f were synthesized from coralyne (2) by a base catalysed Knoevenagel type reaction. It was shown by photometric and fluorimetric titrations of double stranded and quadruplex DNA to 4b–d as well as by fluorimetric DNA denaturation experiments that these ligands bind to DNA with different binding modes at varying ligand-DNA ratios (LDR). Specifically, the addition of DNA caused initially a hypochromic effect in absorbance and, at a particular LDR, the development of a new red shifted absorption band with a hyperchromic effect. Furthermore, 4b–d induced a significant and selective stabilization of quadruplex DNA towards unfolding (ΔTm = 31.6–32.9 °C at LDR = 5), which is even more pronounced as compared to the parent compound coralyne (2). Most notably, the addition of DNA to the dimethylamino-substituted derivative 4b leads to a new, strongly red-shifted emission band at 695 nm. Hence, this derivative is a fluorescent probe that changes its fluorescence colour from green to red in the presence of DNA and even allows the fluorimetric analysis of living cells by staining of the nucleoli.

(E)-2-[1′-((Diphenylamino)styryl)quinolizinium (3a) and 2,2′-{(phenylimino)-bis[(E)-1′′,1′′′-styryl]}-bis[quinolizinium] (3b) were synthesized, and their interactions with duplex DNA and quadruplex DNA were investigated with a particular focus on their ability to operate as DNA-sensitive fluorescent probes. Due to the significantly different size and steric demand of these quinolizinium derivatives they exhibit different binding modes. Thus, 3a intercalates into duplex DNA and binds through π stacking to quadruplex DNA, whereas 3b favours groove binding to both DNA forms. The emission intensity of these compounds is very low in aqueous solution, but it increases drastically upon association with duplex DNA by a factor of 11 (3a) and >100 (3b) and with quadruplex DNA by a factor of >100 (3a) and 10 (3b), with emission bands between 600 and 750 nm.

It is shown by photometric and fluorimetric analysis, along with supporting theoretical calculations, that hydroxy-substituted benzo[b]quinolizinium derivatives display the characteristic features of organic photoacids. Specifically, the experimental and theoretical results confirm the strong acidity of these compounds in the excited state (pKa* < 0). The combination of the prototropic properties of 8- and 9-hydroxybenzo[b]quinolizinium with the particular solvent–solute interactions of the excited acid and its conjugate base leads to a pronounced fluorosolvatochromism, hence the emission maxima shift from 468 nm (8-hydroxybenzo[b]quinolizinium) or 460 nm (9-hydroxybenzo[b]quinolizinium) in CH3CN to 507 and 553 nm in DMF, respectively. This novel type of photoacid represents several features that may be used for applications as water-soluble fluorescent probes or as a source for the photoinduced supply of acidity.

The photochemistry of cyclic carbonate esters proceeds by the photochemical extrusion of carbon dioxide to give 1, 3-diradicals which produce oxiranes as well as other radical derived species. The corresponding cyclic sulfite esters, upon irradiation, give intermediates that are trapped by alcohols yet generate no oxiranes. These results are consistent with ionic intermediates.

The association of heteroaromatic ligands with DNA is an important and biologically relevant process, because it may have a strong influence on the function of the nucleic acid. As a result, efficient and selective DNA-targeting ligands are considered as promising lead structures for drugs. In this context, we established the quinolizinium ion as a versatile building block for the design of DNA-binding ligands, with the long-term goal to evaluate and understand the structural parameters that govern the association of cationic hetarenes with DNA. In this account we demonstrate that annelated quinolizinium derivatives are easily available and that their structure and substitution pattern are highly variable. Most notably, the availability of several derivatives with different size and shape enables the assessment of structure–property relationships regarding their DNA-binding properties. It is shown with exemplary case studies that the systematic variation of the ligand structure, along with analysis of the binding parameters, can be employed to analyze the structural requirements of a ligand to bind to different DNA forms, such as triplex, quadruplex and abasic site-containing DNA. 1 Introduction 2 Association of Quinolizinium Derivatives with Double-Stranded DNA 3 Association of Quinolizinium Derivatives with Triplex DNA 4 Association of Quinolizinium Derivatives with Quadruplex DNA 5 Association of Quinolizinium Derivatives with Abasic Positions in DNA 6 Conclusion

The dicationic styrylimidazo[1,2-a]pyridinium dyes were synthesized and characterized using H-1 NMR, C-13 NMR, mass spectral techniques and elemental analysis. In addition, their photophysical and DNA-binding properties were investigated. The dyes absorb in the UV region with maxima at 342-358 nm, and the emission spectra of these derivatives show a maximum at 409-475 nm with moderate Stokes shift. It was shown with spectrophotometric, spectrofluorimetric and viscometric titrations as well as with Circular dichroism spectroscopic analysis that the dicationic styrylimidazo[1,2-a]pyridinium dyes associate as groove binders with double-stranded DNA with binding constants in the range of 10(5)-10(6) M-1. Preliminary experiments revealed that these ligands also bind with reasonable affinity to telomeric quadruplex DNA. (C) 2015 Elsevier Ltd. All rights reserved.

9-Arylbenzo[b]quinolizinium derivatives were prepared with base-free Suzuki–Miyaura coupling reactions between benzo[b]quinolizinium-9-trifluoroborate and selected benzenediazonium salts. In addition, the Sonogashira coupling reaction between 9-iodobenzo[b]quinolizinium and the arylalkyne derivatives yielded four novel 9-(arylethynyl)benzo[b]quinolizinium derivatives under relatively mild reaction conditions. The 9-(N,N-dimethylaminophenylethynyl)benzo[b]quinolizinium is only very weakly emitting, but the emission intensity increases by a factor >200 upon protonation, so that this derivative may operate as pH-sensitive light-up probe. Photometric and fluorimetric titrations of duplex and quadruplex DNA to 9-(arylethynyl)benzo[b]quinolizinium derivatives revealed a significant binding affinity of these compounds towards both DNA forms with binding constants of K b = 0.2–2.2 × 105 M−1.

A series of new fluorescent arylstyrylimidazo[1,2-a]pyridines was synthesized and fully characterized. It is observed that the E isomers are stable in the solid state and in solutions. The absorption and emission properties of the compounds changed drastically upon acidification. The compounds showed good thermal stability for practical applications. In addition, antimicrobial, antioxidant, and DNA-cleavage activity of the compounds were examined. The results indicate that the compounds did not show any antimicrobial and antioxidant activity. However, they caused decreased mobility of form I DNA and also showed DNA cleavage activity. (C) 2015 Elsevier B.V. All rights reserved.

A series of novel fluorescent arylstyrylimidazo[1,2-a]pyridines was synthesized and fully characterized. All styryl derivatives have an E-configuration of the vinyl double bond as unequivocally shown by H-1 NMR spectroscopy. It was observed that the E isomers are stable in the solid state; however, the derivatives with strong electron donating dialkylamino substituents underwent partial E-Z isomerization in solution at room temperature. The styryl derivatives absorb in the UV or visible region and emit light with moderate Stokes shifts. These compounds exhibit fluorosolvatochromism, namely the emission band is red shifted with increasing solvent polarity. Moreover, the absorption and emission properties of the styryl derivatives change drastically upon acidification, as the protonation of the nitrogen atoms of the imidazo[1,2-a]pyridine ring increases the donor-acceptor interplay of the pi system. (C) 2014 Elsevier Ltd. All rights reserved.

A supramolecular five-component cascade is presented that enables light-controlled transport of an in situ modified ligand between three host systems based on the different complexation preferences of cyclodextrin, cucurbituril, and double-stranded DNA. The results point out novel approaches for the control of drug-DNA interactions in DNA-targeting therapy.

A series of monomeric and homodimeric 4-alkoxystyryl(pyridinium) dyes was synthesized and their DNA-binding properties were investigated. We found that the length of the alkyl substituent has a crucial influence on the binding mode of the dyes, although the structure of the DNA-binding unit is the same for all compounds. Remarkably, mono- and bis-styryl derivatives comprising an oxodecyl chain represent the rare examples of small molecules that bind to the major groove of DNA. We have also demonstrated that the dyes, except the monostyryl dye with a bromopropyl substituent, form chiral aggregates in the presence of double-stranded DNA.

© 2018 Elsevier B.V.An improved microwave-induced synthesis of five ethidium derivatives (Ethidium derivatives, 2a–d) is presented. As the derivatives 2a–d have been proposed previously to be telomerase inhibitors, the binding interactions of these ethidium derivatives with G-quadruplex DNA were evaluated by means of photometric and fluorimetric titration, thermal DNA denaturation, CD and 1H NMR spectroscopy. In particular, the compound bearing 3,8-bis(pyrrolidin-1-yl)propanamido substituent 2a exhibits high selectivity for G-quadruplex DNA relative to duplex DNA.

The solvatochromic 9-hydroxybenzo[b]quinolizinium ion is shown to operate as fluorescent probe for the detection of water in acetonitrile. The dual fluorescence of this photoacid and its dependence on the content of water in the medium enable the ratiometric analysis of the fluorescence data. Graphical Abstract ᅟ.

Biaryl derivatives that consist of one DNA-intercalating unit and a sterically demanding component exhibit a specific behavior towards abasic site-containing DNA (AP-DNA) as determined by thermal DNA denaturation experiments, spectrometric titrations and CD spectroscopic analysis. Specifically, these ligands strongly stabilize AP-DNA towards dissociation, whereas they do not or only marginally affect the melting temperature of regular duplex DNA.

Tumortherapie, bildgebende Diagnostik, Fluoreszenzmikroskopie und schaltbare Materialien nutzen und profitieren von photochemischen und photophysikalischen Methoden.

Two dibenzobarrelene derivatives were synthesized that are covalently linked to a (S)-BINOL unit through an oxymethylene (1b) or ethylenedioxymethylene (1c) unit, and their photoreactivity was examined. Irradiation of 1b in acetone resulted in a di-π-methane rearrangement to give diastereoselectively one dibenzosemibullvalene isomer. Experimental and theoretical data point to a directing effect of the BINOL auxiliary based on steric repulsion. The derivative 1c with a longer linker between the BINOL unit and the dibenzobarrelene is photoinert, presumably because of fast competing relaxation processes in the excited state.

Boronobenzo[b]quinolizinium derivatives exhibit several favorable properties for the fluorimetric detection of hydrogen peroxide, namely quantitative transformation to a product whose emission maximum is well separated from the one of the substrate, water solubility, and the ability to operate in living cells.

The visualization of cell components or processes within cells is an essential task in bioanalytical chemistry. Specifically, the fluorimetric detection of biomacromolecules has developed as a key technique in this research area, mainly because emission spectroscopy is a highly sensitive and straightforward method with relatively few demands on the equipment. As a consequence, several fluorescent probes have been established that enable the selective detection of cells or cellular components. For example, DNA–fluorophore conjugates, peptide-based molecular beacons, groove-binding cyanine dyes, and light-cleavable caged dyes were shown to operate as DNA stains in live cells. Similarly, it was demonstrated that appropriately substituted metallointercalators have a high propensity to bind to cellular DNA and thus enable its fluorimetric detection, or, in some cases, the detection of other cell components. 11] The same principle was applied to detect RNA in nucleoli and the cytoplasm with a 2,7-carbazole derivative. Furthermore, exciton-controlled hybridization-sensitive fluorescent oligonucleotide (ECHO) probes allow multicolor RNA imaging in cells. Recently, a chemosensor has been presented that enables the fluorimetric differentiation of quadruplex DNA from other nucleic acids in cells. Moreover, it has been shown that the fluorimetric discrimination of regions with different polarities may be accomplished in cells with quinoxaline derivatives. Along these lines, the use of near-infrared (NIR, 650–900 nm) fluorescent probes is advantageous for biological applications, because NIR fluorophores exhibit low or almost no phototoxicity, relatively deep penetration into tissue, and negligible interference with the autofluorescence of cells. We have shown recently that benzo[b]quinolizinium derivatives may be functionalized such that the fluorescence is quenched by different independent deactivation pathways and that the association with biomacromolecules results in light-up effects and shifts in the emission energy. In some cases, separate deactivation channels enable the indepenACHTUNGTRENNUNGdent or even simultaneous detection of DNA and metal ions with one chemosensor. In this context, we synthesized 9-(4-dimethylamino)benzo[b]quinolizinium (1a), which exhibits a very low emission quantum yield, presumably caused by deactivation of the excited state by torsional relaxation and photoinduced electron transfer (PET) or charge shift (CS). Notably, some structural features of the derivative 1a resemble aminophenylpyridinium derivatives such as 2, which have been used as fluorescent probes in nerve membranes, and Thioflavin T (3), which has been applied for fluorimetric analysis of amyloid fibril formation. Therefore, we proposed that the derivative 1a may represent a complementary fluorimetric tool for the selective analysis of biomacromolecules, especially considering our experience with the benzo[b]quinolizinium ion as a ligand for DNA and proteins. Herein, we demonstrate that different physiologically relevant host systems are stained with the chemosensor 1a, most remarkably with different emission wavelengths and intensities. In addition, we show that, due to these properties, the chemosensor 1a represents one of the rare examples of probes that stain cells with multicolored fluorescence.

3-Hydroxynaphtho[1,2-b]quinolizinium was synthesized by cyclodehydration route and its optical properties in different media were investigated. The absorption and emission spectra of this compound depend on the pH of the solution. Thus, at higher pH values the deprotonation yields a merocyanine-type dye that exhibits significantly red-shifted absorption bands and causes a dual emisson, i.e., a combination of emission bands of the hydroxyquinolizinium and its deprotonated form. Whereas this compound is a weak acid in the ground state (pK a = 7.9), it has a strongly increased acidity in the excited state (pK a * = 0.4). As a result, the blue-shifted fluorescence of the hydroxyquinolizinium becomes dominant only under strongly acidic conditions. In addition, it is shown that 3-hydroxynaphtho[1,2-b]quinolizinium binds to cucurbit[7]uril (CB[7]) with moderate affinity (K b = 1.8 × 104 M−1, pH 5) and that the pK a and pK a * values of this ligand increase by about two to three orders of magnitude, respectively, when bound to CB[7].

Regiospecific C–N photocyclization of mono- and bis-styryl-substituted N-heterocycles was investigated. We demonstrated that the C–N regiospecificity of the photoinduced electrocyclization is a general feature of ortho-styryl-substituted N-heterocycles comprising one and two nitrogen atoms. This phototransformation provides a straightforward synthesis of the pharmaceutically important benzo[c]quinolizinium cation and its aza-analogues. Noticeably, bis-styryl derivatives undergo only one-fold cyclization with the second styryl fragment remaining uninvolved in the cyclization process. Photocyclization products of monostyryl derivativatives intercalate into calf thymus DNA (ct DNA), whereas photocyclization products of bis-styryl derivativatives possess a mixed binding mechanism with ct DNA. The results can be used for development of novel DNA-targeting chemotherapeutics based on benzo[c]quinolizinium derivatives.

The association of heteroaromatic ligands with DNA is an important and biologically relevant process, because it may have a strong influence on the function of the nucleic acid. As a result, efficient and selective DNA-targeting ligands are considered as promising lead structures for drugs. In this context, we established the quinolizinium ion as a versatile building block for the design of DNA-binding ligands, with the long-term goal to evaluate and understand the structural parameters that govern the association of cationic hetarenes with DNA. In this account we demonstrate that annelated quinolizinium derivatives are easily available and that their structure and substitution pattern are highly variable. Most notably, the availability of several derivatives with different size and shape enables the assessment of structure–property relationships regarding their DNA-binding properties. It is shown with exemplary case studies that the systematic variation of the ligand structure, along with analysis of the binding parameters, can be employed to analyze the structural requirements of a ligand to bind to different DNA forms, such as triplex, quadruplex and abasic site-containing DNA. 1 Introduction 2 Association of Quinolizinium Derivatives with Double-Stranded DNA 3 Association of Quinolizinium Derivatives with Triplex DNA 4 Association of Quinolizinium Derivatives with Quadruplex DNA 5 Association of Quinolizinium Derivatives with Abasic Positions in DNA 6 Conclusion

Cationic biaryl derivatives were synthesized by Suzuki–Miyaura coupling of 3-bromonaphtho[1,2-b]quinolizinium bromide with arylboronic acids. The resulting cationic biaryl derivatives exhibit pronounced fluorosolvatochromic properties. First photophysical studies in different solvents showed that the emission energy of the biaryl derivatives decreases with increasing solvent polarity. This red-shifted emission in polar solvents is explained by a charge shift (CS) in the excited state and subsequent solvent relaxation. Furthermore, the polarity of protic polar and aprotic polar solvents affects the emission energy to different extent, which indicates a major influence of hydrogen bonding on the stabilization of the ground and excited states.

Cationic biaryl derivatives were synthesized by Suzuki–Miyaura coupling of 3-bromonaphtho[1,2-b]quinolizinium bromide with arylboronic acids. The resulting cationic biaryl derivatives exhibit pronounced fluorosolvatochromic properties. First photophysical studies in different solvents showed that the emission energy of the biaryl derivatives decreases with increasing solvent polarity. This red-shifted emission in polar solvents is explained by a charge shift (CS) in the excited state and subsequent solvent relaxation. Furthermore, the polarity of protic polar and aprotic polar solvents affects the emission energy to different extent, which indicates a major influence of hydrogen bonding on the stabilization of the ground and excited states.

The solvatochromic emission properties of five naphthoylurea derivatives with different substitution patterns at the naphthoylurea functionality were investigated, with a particular focus on the influence of inter- and intramolecular H-bonding interactions. The bathochromic shifts of the emission maxima correlate well with the acceptor number or Catalán's acidity of the solvent (Δλ = 47-86 nm), indicating an excited species with a pronounced negative charge that is stabilized by H-bond donating (HBD) solvents. In media with restricted free volume the formation of the charged species is not favored, because the required conformational change to establish an intramolecular charge transfer (ICT) between the fluorophore and the acylurea substituent is hindered, and the emission mainly originates from the locally excited state. This relationship between the alignment of the naphthoyl carbonyl functionality relative to the naphthyl ring and the spectroscopic shift was confirmed by the comparison of the ground state conformation and the emission spectra of the naphthoylurea derivatives in the solid state. Time-resolved experiments revealed different excited entities, whose lifetimes are significantly influenced by the HBD properties and the temperature of the environment. With few exceptions the naphthoylurea derivatives exhibit only two emissive species in the nanosecond range. All experimental data point to conformational relaxation and solvent reorganization leading to the cis and trans isomers of one preferential conformer with respect to the acylurea unit. The structure of the preferred conformation is mainly determined by the possible inter- or intramolecular H-bonds and is therefore also strongly influenced by the HBD and H-bond accepting (HBA) properties of the polar solvents. As the NH groups of the acylurea functionality contribute mainly to the entire inter- and intramolecular H-bond arrangement the variation of the substitution pattern of the urea unit, specifically the presence and position of the NH groups, leads to derivatives with significantly different steady-state and time-resolved emission properties.