MediaChrom: Discovering a Class of Pyrimidoindolone-Based Polarity-Sensitive Dyes

Abstract

A small library of six polarity-sensitive fluorescent dyes, nicknamed MediaChrom, was prepared. This class of dyes is characterized by a pyrimidoindolone core fitted out with a conjugated push-pull system and a carboxy linker for a conceivable coupling with biomolecules. The optimized eight-step synthetic strategy involves a highly chemo- and regioselective gold-catalyzed cycloisomerization reaction. The photophysical properties of MediaChrom dyes have been evaluated in-depth. In particular, the MediaChrom bearing a diethylamino as an electron-donating group and a trifluoromethyl as an electron-withdrawing group displays the most interesting and advantageous spectroscopic features (e.g., absorption and emission in the visible range and a good quantum yield). Promising results in terms of sensitivity have been obtained in vitro on this dye as a membrane/lipophilic probe and as a peptide fluorescent label.

Synthesis and photophysical properties of isocoumarin-based D-π-A systems

“…The ability of amino substituent to improve the fluorescence properties of isocoumarin derivatives has been already observed by Satoh and Miura. 11b Regarding the choice of the EW groups, we privileged those groups that display more interesting features in the MediaChrom 8 series, and in particular the trifluoromethyl group, a substituent hardly investigated in this context. 13 Thus, commercially available 2-bromo-5-nitrobenzoic acid 2a was easily converted into the corresponding methyl ester 3a 14 and alkynylated under standard Sonogashira conditions 15 to give 2alkynylbenzoates 4a,b in very good yields.…”

“…A few years ago, we brought our contribution in this field synthesizing a small library of polaritysensitive fluorescent dyes -nicknamed MediaChrom 8 (Figure 1) -characterized by a heterocyclic pyrimidoindolone backbone, which displayed interesting photophysical profiles. Within our enduring interest in the development of new strategies for the synthesis of functionalized heterocycles starting from alkynes, 9 we recently reported a selective and high yielding approach to isocoumarin nucleus.…”

“…The ED and EW groups of the push-pull system were selected taking into account the recent review of Filip Bures, 7 together with our previous experience. 8 The photophysical properties of the D--A isocoumarins synthesized were evaluated and a rationale on the effect of the substituents on the solvatochromic shift was delineated. In this paper we describe our results.…”

Indole‐2‐Carboxaldehyde: An Emerging Precursor for the Construction of Diversified Imperative Skeleton

“…[30a] The compound Mediachrom, containing a pyrimidoindole moiety in its scaffold, is used as a polarity-sensitive fluorescent dye. [37,38] Hinckdentine A, an alkaloid isolated from the bryozoan Hincksinoflustra denticulate, contains biologically important dihydrotryptamine and dihydropyrimidine units in its framework. [30b] The 2-substituted 5H-pyrimido [5,4-b]indoles obtained from 3-haloindole-2-carboxaldehydes constitute the core framework of several compounds associated with PDE inhibition, iono tropic, chronotropic activities and benzodiazepine receptor binding activity.…”

Exploiting the σ-phylic properties of cationic gold(i) catalysts in the ring opening reactions of aziridines with indoles

“…23.N,N-Diethyl-1H-indol-6-amine (1m). A solution of 2 M NaOH (3.7 mL, 7.49 mmol) was added to a stirring solution of 6-(N,N-diethylamino)-1-( phenylsulfonyl)-1H-indole27 (200 mg, 0.61 mmol) in 7 mL of MeOH and heated at 85°C under a nitrogen atmosphere. The reaction mixture was stirred for 24 h until no more starting product was detectable by TLC analysis.…”