New class of 8-aryl-7-deazaguanine cell permeable fluorescent probes

Dhimitruka, Ilirian; Eubank, Timothy D.; Gross, Amy C.; Khramtsov, Valery V.

doi:10.1016/j.bmcl.2015.08.054

Cited by 5 publications

(7 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One fruitful design strategy for fluorescent analogues of the purine bases adenine and guanine has been to substitute these molecules at position C8 with conjugating groups, ,− leading, among others, to the subject of the present study: 8-vinylguanine (8vG), whose structure is shown in Figure . The FBA 8vG was synthesized by Nadler and co-workers as an isomorphic fluorescent analogue of guanine, and it was reported to combine several properties that are favorable for application in studies of DNA structure. , The replacement of guanine with 8vG in double-stranded DNA results in only a minor destabilization of the duplex .…”

Section: Introductionmentioning

confidence: 99%

Theoretical Study of the Photophysics of 8-Vinylguanine, an Isomorphic Fluorescent Analogue of Guanine

2016

View full text Add to dashboard Cite

Paving the way for the application of the algebraic-diagrammatic construction scheme of second-order (ADC(2)) to systems based on the guanine chromophore, we demonstrate the this excited-state electronic structure method provides a realistic description of the photochemistry of 9H-guanine, in close agreement with the benchmark provided by the CASPT2 method. We then proceed to apply the ADC(2) method to the photochemistry of 8-vinylguanine (8vG), a minimally modified analogue of guanine which, unlike the naturally occurring nucleobase, displays intense fluorescence, indicative of a much longer-lived excited electronic state. The emissive electronic state of 8vG is identified as an ππ*-type intramolecular charge transfer (ICT) state, in which a charge of roughly -0.2 e is transferred from the guanine moiety onto the vinyl substituent. The main radiationless deactivation pathway competing with fluorescence is predicted to involve the molecule leaving the minimum on the ICT ππ* state, and reaching a region of the S1 adiabatic state where it resembles the La ππ* state of unmodified 9H-guanine. The topology of the La ππ* region of the S1 state favors subsequent internal conversion at a crossing seam with the ground electronic state. The sensitivity of this process to environment polarity may explain the experimentally observed fluorescence quenching of 8vG upon incorporation in single- and double-stranded DNA.

show abstract

Section: Introductionmentioning

confidence: 99%

Theoretical Study of the Photophysics of 8-Vinylguanine, an Isomorphic Fluorescent Analogue of Guanine

2016

View full text Add to dashboard Cite

show abstract

“…While P1 and P4 can be obtained commercially, P2 , P3 , P5 , and P6 were prepared in-house. P2 and P3 were synthesized according to a literature procedure, with analytical data consistent with that reported previously. − The synthesis of P5 and P6 began with Friedel–Crafts acylation of fluoranthene using acetyl chloride and AlCl 3 in dry dichloromethane (DCM) under Schlenk conditions, to afford both the 3-acetyl ( 1 ) and 8-acetyl ( 2 ) fluoranthene derivatives . Because of the chemical similarity of the two products, separation was performed by column chromatography using very fine grade silica (10–14 μm, LC35A Davisil, Grace Davison) to fully resolve the products.…”

Section: Resultsmentioning

confidence: 99%

Extending the Excitation Wavelength of Potential Photosensitizers via Appendage of a Kinetically Stable Terbium(III) Macrocyclic Complex for Applications in Photodynamic Therapy

et al. 2017

View full text Add to dashboard Cite

The development of viable photodynamic therapy protocols is often hindered by photosensitizers that require high-energy UV irradiation that has limited potential for clinical use due to its low tissue penetration. Herein, we report a strategy for extending the excitation wavelength of potential photosensitizers via the covalent attachment of a terbium(III)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate complex (DO3A-Tb). The method was systematically demonstrated with a series of polycyclic aromatic hydrocarbons (naphthalene, phenanthrene, anthracene, pyrene, and fluoranthene) to prepare six new complexes (Tb1-Tb6) with bathochromic shifts that extended into the visible region. Determination of their quantum yields for singlet oxygen (O) production at 350 and 420 nm showed significant enhancements from the parent molecule in all cases. Cell viability studies on cervical cancer cells (HeLa) and noncancerous MRC-5 cells showed no measurable cytotoxicity for all complexes prior to light irradiation. However, after irradiation at 420 nm (20 min, 9.27 J cm), Tb3-Tb6 were phototoxic to HeLa cells with IC values between 14.3-32.3 μM. Cell morphological studies and fluorescence microscopy with live/dead cell stains confirmed these findings. In addition, these complexes were highly stable in human blood plasma, with no significant degradation observed after 96 h at 37 °C. This excellent phototoxicity profile and high stability in blood plasma, coupled with the moderately lipophilic nature of the complexes, favorably indicate the potential of DO3A-Tb as a heavy atom-bearing moiety for modification of potential photosensitizers into ideal phototherapeutic drug candidates with longer excitation wavelengths for in vivo application.

show abstract

“…Recently, Dhimitruka et al synthesized the base 8-phenyl-7-deazaguanine 21, which shows fluorescence. 29 However, it was observed that compound 21 only develops strong fluorescence in aprotic polar solvents, for instance in DMSO (Φ = 0.96), whereas fluorescence decreases strongly in aqueous medium (Φ = 0.12).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Next, fluorescence measurements were performed in DMSO (Figure 2a). The fluorescence intensity of nucleoside 2 (Φ = 0.81) is slightly lower compared to that of nucleobase 21 (Φ = 0.96), 29 whereas other nucleosides (1, 3, and 4) are almost nonfluorescent.…”

Section: The Journal Of Organic Chemistrymentioning

confidence: 86%

7-Deaza-2′-deoxyguanosine: Selective Nucleobase Halogenation, Positional Impact of Space-Occupying Substituents, and Stability of DNA with Parallel and Antiparallel Strand Orientation

Ingale

Seela

2016

J. Org. Chem.

View full text Add to dashboard Cite

The positional impact of phenyl or phenyltriazolyl residues on the properties of 7-deaza-2'-deoxyguanosine, such as fluorescence, sugar conformation, and stability in DNA and DNA-RNA double helixes was studied. To this end, regioselective iodination protocols were developed for 7-deaza-2'-deoxyguanosine affording the 7- and 8-iodo isomers. The aromatic side chains were introduced by Suzuki-Miyaura cross-coupling or click reaction. Only the 8-phenyl nucleoside shows strong fluorescence in polar aprotic solvents accompanied by solvatochromism. The conformation of the sugar moiety was shifted toward S due to the bulky 8-substituent. Phosphoramidite building blocks and oligonucleotides were synthesized. 8-Substituted 7-deaza-2'-deoxyguanosines destabilize canonical (aps) DNA as well as DNA with parallel strand (ps) orientation. The base pair stability was maintained when the space-occupying substitutes were located at the 7-position. Unexpectedly, the bulky phenyltriazolyl "click" residue is well-accommodated at the 7-position of ps DNA and even led to a stabilization of the parallel double helix. CD spectra indicate that functionalization leads only to local distortion of the double helix while the overall structure of aps and ps DNA is maintained.

show abstract

New class of 8-aryl-7-deazaguanine cell permeable fluorescent probes

Cited by 5 publications

References 21 publications

Theoretical Study of the Photophysics of 8-Vinylguanine, an Isomorphic Fluorescent Analogue of Guanine

Theoretical Study of the Photophysics of 8-Vinylguanine, an Isomorphic Fluorescent Analogue of Guanine

Extending the Excitation Wavelength of Potential Photosensitizers via Appendage of a Kinetically Stable Terbium(III) Macrocyclic Complex for Applications in Photodynamic Therapy

7-Deaza-2′-deoxyguanosine: Selective Nucleobase Halogenation, Positional Impact of Space-Occupying Substituents, and Stability of DNA with Parallel and Antiparallel Strand Orientation

Contact Info

Product

Resources

About