Acridinium Derivatives Research Articles

Selective fluorescence sensors for Cu2+ and Hg2+ ions using acridinium-polymer complexes

The photophysical properties of two acridinium derivatives, 9-phenyl-10-methylacridinium (Ph-Arc+) and 9-mesityl-10-methyl acridinium (Mes-Acr+) were investigated in aqueous solutions of poly(methacrylic acids) (PMAA) at various pH values with various polymer to dye (R/D) ratios. In acidic conditions, PMAA effectively turned on the emission of both acridinium derivatives. Micromolar concentrations of copper (II) ions can selectively turn off the emission of dye/PMAA mixtures with a linear response range from 0.50 to 10.0 µM and a detection limit as low as 0.38 µM. In near neutral conditions, Mes-Acr+ in PMAA solutions displayed extremely weak emission. However, trace amounts of Hg2+ ions can instantly turn on the emission with a low detection limit of 43.6 nM and a linear range between 1.0 to 10.0 µM. This analytical method is fast, cost-effective, and environmentally friendly, as it is conducted in 100 % aqueous solution with commercial acridinium derivatives and a biocompatible polymer.

Density functional theory‐based rapid and accurate estimation of reduction potentials of acridinium derivatives in ground and excited state

AbstractWe devised a quantum chemical simulation protocol that can rapidly and accurately predict ground and excited state reduction potentials (E0 and E*, respectively) of acridinium photoredox catalysts (PCs). To bypass time‐consuming excited state geometry optimizations, we used ground state equilibrium geometries to compute the electronic energy of excited states, which provides reasonable E0 and E* estimates. The contribution of Hartree‐Fock exchange (HFX) in density functionals was systematically varied to estimate E0 and E*. In addition to reproducing experimental results, physically sensible models, such as correct descriptions of exciton behavior, are highly necessary. Based on the exciton correlation values, the appropriate amount of HFX in the B3LYP functional was determined to be 30 % to yield physically sensible bound electron‐hole pairs for small organic molecules. We also investigated the impact of basis sets on the predictability of E0 and E*. Geometry optimizations with B3LYP‐D2(HFX 20 %)/6‐31G and single point energy refinement with (TD‐)B3LYP‐D2(HFX 30%)/6‐311++G(d,p) yielded the best results. The transferability of the suggested protocol was confirmed with a test set consisting of eight acridinium derivatives. This study can provide reasonably accurate results with relatively small amounts of computational resources, and it is therefore expected to greatly contribute to the development of new acridinium PCs.

Fluorescent turn-off sensor for Cu2+ and Fe3+ ions in 100% aqueous media with a biocompatible polymer

A sensitive analytical method using an acridinium derivative in 100% aqueous media to detect Cu (II) and Fe (III) ions been developed. The photophysical properties of a thiophene-phenylanilide-acridinium triad (TPA) in acidic poly(methylacrylic acid) (PMAA) solution are altered in the presence of various metal ions. While dye/PMAA mixtures in acidic condition emit strongly at around 540 nm, Fe3+ and Cu2+ ions can each quench the charge shift state (CSH) emission significantly. The linear range of response to Cu2+ is 1 to 9.0 μM and to Fe3+ is 4 to 68 μM. The detection limit is 0.11 μM for Cu2+ ions and 0.60 μM for Fe3+ ions. Stern-Volmer plots showed more than one quenching mechanism for Fe3+ ions and the Benesi-Hilderbrand plot indicates a 1:1 binding ratio between dye/PMAA mixture and metal ions. While Cd2+ and Hg2+ ions interfere with the quenching, addition of iodide ions completely resolves the interference problem for both ions. The quenching by Fe3+ ions involved the inner-filter effect and partial removal of dye molecules from the hydrophobic interior of PMAA due to competitive binding. The quenching by Cu2+ ions is likely due to photoinduced electron transfer from the charge shift state of dye molecules to the partly filled d-orbitals of Cu2+ ions, leading to weaker CSH emission. Computer simulation supports the model in which dye molecules incorporate into the hydrophobic pockets formed due to the coordination of Cu2+ ions with carboxyl groups on PMAA chains.

Tricyclic Aza-Andrographolide Derivatives from Late-Stage Hydroamination and Their Anti-human Coronavirus (Anti-HCoV) Activity.

A late-stage functionalization (LSF) of the natural product andrographolide for the efficient assembly of a range of structurally interesting and diverse tricyclic-aza derivatives was developed. The key to the diversification is a photo-catalyzed intramolecular hydroamination reaction, and acridinium derivatives were demonstrated to be the optimal catalysts. Additionally, the synthesized tricyclic aza-andrographolide derivatives were found to inhibit human coronavirus with high potency.

Solvent Effect on the Chemiluminescence of Acridinium Thioester: A Computational Study.

Chemiluminescent labelling, which is one of the promising procedures of modern immunodiagnostics, is increasingly carried out using acridinium derivatives, an oxidant, and an alkaline aqueous environment. However, the efficiency of the chemiluminescence of luminol or acridinium esters is higher in non-aqueous solvents such as dimethyl sulfoxide or acetonitrile. Therefore, the search for a new environment for the chemiluminescence reaction, especially the one characterized by a higher quantum yield of chemiluminescence, is one of the aims of current research. Using computational methods (DFT and TD DFT with PCM model of solvent), we examined thermodynamic and kinetic data concerning the chemiluminescence and competitive dark pathways. Our results suggest that better characteristics of the chemiluminescence reaction of acridinium thioester are observed in nonpolar solvents, such as methylcyclohexane, n-hexane and n-pentane, than in aqueous media used so far. Further experimental verification is necessary to confirm the possible application of proposed nonpolar solvents in chemiluminescent labelling and hence in immunodiagnostics.

Phosphorescence Enables Identification of Electronic State for Acridinium Salt in Solutions.

Acridinium derivatives are an important class of photocatalysts, where the interaction between the catalyst and the environment is under-reported. Here we show that the Lewis acidic acridinium salt exhibits various degrees of interactions with different Lewis bases, including water (HOH), methanol (CH3OH), tetrahydrofuran (THF, ROR), amines (R3N), and tert-butoxide (RO-) due to distinct physical properties stemming from different resonance forms. Interactions with water and methanol produce almost identical 1H NMR spectra but lead to drastically different UV absorption and luminescence emission, particularly phosphorescence; interactions with CH3OH/methanol and THF, which are differentiated by heat calorimetry titration, share the same luminescence spectra but show two different sets of 1H NMR peaks. These distinct physical properties could only be revealed by a combination of NMR and molecular fluorescence/phosphorescence spectroscopic methods. The current report serves as an example of using phosphorescence spectroscopy as a complementary tool for identifying interactions between organic molecules.

Effects of the Surface Charge Density of Clay Minerals on Surface-Fixation Induced Emission of Acridinium Derivatives.

Surface-fixation induced emission is a fluorescence enhancement phenomenon, which is expressed when dye molecules satisfy a specific adsorption condition on the anionic clay surface. The photophysical behaviors of two types of cationic acridinium derivatives [10-methylacridinium perchlorate (Acr+) and 10-methyl-9-phenylacridinium perchlorate (PhAcr+)] on the synthetic saponites with different anionic charge densities were investigated. Under the suitable conditions, the fluorescence quantum yield (Φf) of PhAcr+ was enhanced 22.3 times by the complex formation with saponite compared to that in water without saponite. As the inter-negative charge distance of saponite increased from 1.04 to 1.54 nm, the Φf of PhAcr+ increased 1.25 times. In addition, the increase in the negative charge distance caused the increase in the integral value of the extinction coefficient and the radiative deactivation rate constant (kf) and the decrease in the nonradiative deactivation rate constant. It should be noted that the 2.3 times increase in kf is the highest among the reported values for the effect of clay. From these results, it was concluded that the photophysical properties of dyes can be modulated by changing the charge density of clay minerals.

A rainbow of acridinium chemiluminescence.

Multicolor chemiluminescent acridinium derivatives were synthesized by attaching various common fluorophores to the N10 -acridinium position through a piperazine linker. Triggering of each acridinium derivative using alkaline hydrogen peroxide resulted in a chemiluminescence spectrum dominated by a strong emission (>95%) from the attached fluorophore. The highly quenched emission from the triggered acridinium, acting as a donor, points to a highly efficient intramolecular energy transfer in acridinium-based chemiluminophore-fluorophore tandems. A variable, and in many cases minimal, spectral overlap between the donor emission and the acceptor absorption may indicate that in such tandems the energy transfer follows the Dexter electron exchange mechanism. Moreover, fluorophores affixed through the acridinium 9-position produce a typical acridinium emission profile, demonstrating the need for close distances and favorable intramolecular orientation of the donor and acceptor moieties for the energy transfer to occur. A family of red-shifted chemiluminescent labels, all sharing a uniform triggering method, will find immediate application in multicolor ligand-receptor assays. Along with the multiplexing capabilities, the red-shifted chemiluminescent detection offers a higher tolerance to green-colored biological interferences and will therefore benefit many screening and diagnostic clinical tests.

Thermodynamic and kinetic studies of hydride transfer from Hantzsch ester under the promotion of organic bases

Thermodynamics and kinetics for base-promoted hydride transfer (BPHyT) were investigated with Hantzsch ester and acridinium derivatives as model compounds.

Copper-Catalyzed N,N-Diarylation of Amides for the Construction of 9,10-Dihydroacridine Structure and Applications in the Synthesis of Diverse Nitrogen-Embedded Polyacenes.

We reported herein CuI/DMEDA catalyzed N,N-diarylation reaction of amides with various di(o-bromoaryl)methanes to produce diverse 9,10-dihydroacridine derivatives. The resulting 9,10-dihydroacridine derivatives were oxidized selectively under mild conditions to afford acridine, acridinone, and acridinium derivatives. The copper-catalyzed N,N-diarylation reaction coupled with oxidative aromatization reaction enabled the facile construction of nitrogen atom-embedded tetracenes and pentacenes of different ortho-fused patterns. The luminescence properties, especially the effect of fusion pattern on fluorescence emission of acquired N-polycenes, were also demonstrated.

Thermodynamic study of the adsorption of acridinium derivatives on the clay surface.

In this study, the adsorption behavior of mono-cationic acridinium derivatives on a synthetic clay mineral (Sumecton SA) was investigated. The acridinium derivatives were adsorbed on the clay surface without aggregation, as found from the changes in the absorption spectra of the acridinium derivatives with SSA and without SSA represented by two-component equilibrium systems of adsorbed and non-adsorbed components. Following the Langmuir isotherm analysis, the adsorption equilibrium constants and maximum adsorption amounts were determined for acridinium derivatives, and the Gibbs free energy change (ΔG) was calculated to be in the range of −33.8 to 40.0 kJ mol−1 from the adsorption equilibrium constants. These results indicated that the adsorption of acridinium derivatives on the clay surface was an exergonic reaction. Moreover, thermodynamic parameters such as enthalpy change (ΔH) and entropy change (ΔS) were obtained from the temperature effect experiments. For all acridinium derivatives, ΔH (from −7.82 to −26.0 kJ mol−1) and ΔS (0.047–0.088 kJ mol−1 K−1) were found to be negative and positive, respectively. It was suggested that not only electrostatic interactions, but also van der Waals forces and hydrophobic interactions played an important role in the adsorption of cationic aromatic molecules on the clay surface. Because these thermodynamic parameters showed a strong correlation with the molecular cross-sectional area of acridinium derivatives, it was suggested that the contribution of hydrophobic interactions became smaller as the molecular cross-sectional area became larger.

Charge-transfer heptamethine dyes for NIR singlet oxygen generation.

A heptamethine-based charge-transfer dye was designed based on previous evidence of triplet state formation in orthogonal charge-transfer partners and calculations suggesting the formation of a charge-transfer state in heptamethine dye derivatives. An acridinium derivative of IR-1061 was subsequently synthesized and characterized, demonstrating photochemical reactivity at wavelengths over 1000 nm.

Structural considerations on acridine/acridinium derivatives: Synthesis, crystal structure, Hirshfeld surface analysis and computational studies

This article describes a detailed study of the molecular packing and intermolecular interactions in crystals of four derivatives of acridine, i.e. 9-methyl-, 9-ethyl, 9-bromomethyl- and 9-piperidineacridine (1, 2, 3 and 4, respectively) and three 10-methylacridinium salts containing the trifluoromethanesulphonate anion and 9-vinyl-, 9-bromomethyl, and 9-phenyl-10-methylacridinium cations (5, 6 and 7, respectively). The crystal structures of all of the compounds are stabilized by long-range electrostatic interactions, as well as by a network of short-range C–H⋅⋅⋅O (in hydrates and salts 3 and 5–7, respectively), C–H⋅⋅⋅π, π–π, C–F⋅⋅⋅π and S–O⋅⋅⋅π (in salts 5–7) interactions. Hirshfeld surface analysis shows that various intermolecular contacts play an important role in the crystal packing, graphically exhibiting the differences in spatial arrangements of the acridine/acridinium derivatives under scrutiny here. Additionally, computational methods have been used to compare the intermolecular interactions in the crystal structures of the investigated compounds. Computations have confirmed the great contribution of dispersive interactions for crystal lattice stability in the case of 9-substituted acridine and electrostatic interactions for the crystal lattice stability in the case of 9-substituted 10-methylacridinium trifluoromethanesulphonates. The value of crystal lattice energy and the electrostatic contribution in the crystal lattice energy of monohydrated acridine derivatives have confirmed that these compounds have behave as acridinium derivatives.

Determination of Cr(VI) with Selective Sensing of Cr(VI) Anions by a PVC‐Membrane Electrode Based on Quinaldine Red

AbstractA dichromate‐selective PVC‐membrane electrode based on Quinaldine Red (an acridinium derivative) is described. The electrode exhibits rapid (< 30 s) and linear response to the activity of Cr(VI) anions in the range of 5.2 × 10−6 −1.0 × 10−1 M dichromate with the limit of detection 2.5 × 10−6 Mof Cr2O72−. The sensor is used as an indicator electrode in potentiometric determination of Cr(VI) anions and is also suitable for end‐point indication in the titrations of proper metal ions with dichromate under laboratory conditions. The proposed electrode has been applied to the direct potentiometric determination of Cr(VI) anions in water samples with satisfactory results.

Chromophore/DNA Interactions: Femto- to Nanosecond Spectroscopy, NMR Structure, and Electron Transfer Theory

The mechanism of photoinduced hole injection into DNA has been studied using an integrated approach that combines NMR structural analysis, time-resolved spectroscopy, and quantum-chemical calculations. A covalently linked acridinium derivative, the protonated 9-amino-6-chloro-2-methoxyacridine (X+), is replacing a thymine and separated from either guanine (G) or the easier to oxidize 7-deazaguanine (Z) by one adenine.thymine (A.T) base pair. The key features of this donor/acceptor system are the following: (i) In more than 95% of the duplexes, X+ is located in a central, coplanar position between the neighboring A.T base pairs with its long axis in parallel showing minimal twist and tilt angles (<15 degrees). The complementary adenine base is turned out into the extrahelical space. In a minority of less than 5%, X+ is found to be still attached to the duplex. X+ is most probably associated with one of the phosphates, since it is neither intercalated between more remote base pairs nor bound to sugars or grooves. This minority characterized by an excited state lifetime >10 ns gives rise to a small background signal in time-resolved measurements and contributes predominantly to steady-state fluorescence spectra. (ii) Although the intercalation mode of X+ is well defined, the NMR structure reveals that there are two conformations of X+ with respect to the arrangement of its methoxy substituent. In one conformation, the methoxy group is in the plane of the chromophore, while, in the other extraplanar conformation, the methoxy group forms an angle of 70 degrees with the acridinium ring. The fluorescence decay of 5'-ZAX and 5'-GAX tracts can be fitted to a biexponential function with similar amplitudes, reflecting the oxidation dynamics of G and Z, with the slower rate being determined by larger thermal activation energy. The attribution of biexponential electron transfer (ET) dynamics to the bimodal orientation of the methoxy group at the acridinium is supported by quantum-chemical calculations. These predict a larger free energy change for hole transfer in the nonplanar conformation as compared to the planar one, whereas the difference in the electronic couplings is negligible. (iii) Kinetic studies of the directionality of the 1(X+)* induced hole injection reveal similarly fast decay components in both directions of the duplex, that is, in 5'-ZAX and 5'-XAZ, with the amplitude of the fast component being significantly reduced in 5'-XAZ. The NMR structure shows that local structural deviations from B-DNA are much more pronounced in the 3'-5' direction than in the 5'-3' direction. According to quantum-chemical calculations, the directionality of charge injection is not a universal feature of the DNA duplex but depends critically on the rotation angle of the aromatic plane of the acridinium within the pi stack. The arrangement of X+ in 5'-ZAX and 5'-XAZ corresponds to a conformation with weak directionality of the electronic couplings. The increased disorder in the 3'-5'direction favors slow hole transfer components at the expense of the fast ones. (iv) A comparison of the hole transfer in 5'-GAX and 5'-ZAG shows that classical Marcus theory can explain the ratio of the charge shift rates of more than 2 orders of magnitude on the basis of a free energy difference between G and Z of 0.3 eV. Both NMR structures and quantum-chemical calculations justify the appreciable neglect of differences of electronic couplings as well as in the reorganization energy in 5'-GAX and 5'-ZAG. Despite the attractive concept for the behavior of floppy DNA oligonucleotides, in this acridinium/DNA system, there is no evidence for conformational gating, that is, for fluctuations in the electronic couplings that permit the ET to occur.

Fluorescence Modulation of Acridine and Coumarin Dyes by Silver Nanoparticles

Silver nanoparticles were synthesized by chemical reduction of silver ions by sodium borohydride in the presence of poly-(N)-vinyl-2-pyrrolidone in solution of short chain alcohols. The nanoparticles are stable in 2-propanol, and the average diameter of the Ag colloid obtained in this solvent is about 6 nm. The photophysical properties of acridinium and coumarin dyes in 2-propanol are affected by the presence of silver nanoparticles. The interaction of silver nanoparticles with acridinium derivative leads to a spectral change of its intramolecular charge transfer (ICT) absorption band. The dye emission increases suddenly with the initial addition of the Ag metal nanoparticles, but at a high concentration of the colloid, static fluorescence quenching occurs with a progressive decrease of the fluorescence efficiency. Amino coumarin fluorescence is only quenched by the silver nanoparticles in solution.

Selective Interactions of a Few Acridinium Derivatives with Single Strand DNA: Study of Photophysical and DNA Binding Interactions

Novel acridinium derivatives 1-3, wherein steric factors have been varied systematically through substitution at the ninth position of the acridinium ring, were synthesized and their interactions with single strand and double strand DNA have been investigated through photophysical, biophysical, and microscopic techniques. The acridinium derivative 1 exhibited quantitative fluorescence yields (phi f approximately =1) and high lifetime of 35 ns, while significantly lower fluorescence yields of 0.11 and 0.02 and lifetimes of 3.5 and 1.2 ns were observed for 2 and 3, respectively. The derivatives 1 and 2 having 2-methylphenyl and 2,4-dimethylphenyl substituents at the ninth position of the acridinium ring showed selective interactions with single strand DNA (ssDNA) with association constants of KssDNA = 6.3-6.6 x 10(4) M(-1), while negligible interactions were observed with double strand DNA (dsDNA). In contrast, the derivative 3 with 2,6-dimethylphenyl substitution showed negligible interactions with both ssDNA and dsDNA. Studies with a series of 19-mer oligonucleotides indicate that these derivatives exhibit significant selectivity for the sequences rich in guanosine (ca. 3-fold) as compared to the cytosine-rich sequences. These derivatives with high water solubility and the ability to distinguish between ssDNA and dsDNA through changes in fluorescence emission can be used as fluorescent probes for understanding the role of ssDNA in various biological processes and to study various DNA-ligand interactions.

Novel biotinylated acridinium derivatives: New reagents for fluorescence immunoassays and proteomics

Background The favorable properties of acridinium derivatives over conventional fluorescent probes have attracted considerable interest. These conjugates have found wide utility in tests developed for medical diagnosis providing at least comparable sensitivity to radioimmunoassay (RIA) and enzyme immunoassay (EIA) procedures. Methods In this paper we describe the synthesis, luminescent properties and immunoassay applications of two novel biotinylated acridinium derivatives, 9-(2-biotinyl-oxyethyl)-carboxylate-10-methyl-acridinium triflate, BOCMAT and 9-(2-biotinyl-amidoethyl)-carboxylate-10-methyl-acridinium triflate, BACMAT. Results The chemiluminescence efficiency of the novel reagents is high in polar aprotic solvents and attains detection limits down to 7.28 × 10 − 8 M, while the fluorescence efficiency has its maximum in aqueous solutions with detection limits down to 1.94 × 10 − 10 M. The above novel compounds were applied in the fluorimetric determination of solid phase-immobilized biotinylated mouse IgG and the detection limit was found to be ∼ 1 μg/assay (∼ 7 pmol/assay). Conclusions The new streptavidin-based detection reagents were synthesized can be used for the development of highly sensitive solid-phase fluorescence-based immunoassays and may find important applications in proteomics.

Tuning of Intercalation and Electron-Transfer Processes between DNA and Acridinium Derivatives through Steric Effects

A series of acridinium derivatives 1-6, wherein steric factors have been varied systematically through substitution at the 9 position of the acridine ring, have been synthesized and their DNA interactions have been investigated by various biophysical techniques. The unsubstituted and methylacridinium derivatives 1 and 2 and the o-tolylacridinium derivative 6 exhibited high fluorescence quantum yields (Phi(f)() congruent with 1) and lifetimes (tau = 35, 34, and 25 ns, respectively), when compared with the arylacridinium derivatives 3-5. The acridinium derivatives 1 and 2 showed high DNA binding affinity (K = 7.3-7.7 x 10(5) M(-)(1)), when compared to the arylacridinium derivatives 3-5 (K = 6.9-10 x 10(4) M(-)(1)). DNA melting and viscosity studies establish that in the case of the aryl-substituted systems, the efficiency of DNA binding is in the order, phenyl > p-tolyl > m-tolyl >>>> o-tolyl derivative. The increase in steric crowding around the acridine ring hinders the DNA binding interactions and thereby leads to negligible binding as observed in the case of 6 (o-tolyl derivative). These results indicate that a subtle variation in the substitution pattern has a profound influence on the photophysical and DNA interactions. Further, they demonstrate that pi-stacking interactions of the ligands with DNA are essential for efficient electron transfer between the DNA bases and the ligands. These water soluble and highly fluorescent molecules which differ in their DNA binding mode can act as models to study various DNA-ligand interactions.

On the synthesis and functionalisation of the 4-aza-8,12-dioxa-4,8,12,12c-tetrahydrodibenzo[ cd,mn]pyrenium system

The preparative use of the reaction between tris(2,6-dimethoxyphenyl)carbenium tetrafluoroborate and excess of an arylamine such as 4-methylaniline or 4-bromoaniline to yield firstly the aryl functionalised acridinium derivatives and then further in situ reaction to yield the desired functionalised triangulenium salts was found to be problematic. A preparative route for the triangulenium salts is presented along with a demonstration of the further derivatisation by standard Suzuki coupling reaction.