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Diverse models of intramolecular charge transfer (ICT) have been proposed for interpreting the origin of the charge-transfer (CT) state in donor–acceptor (D–A) dyes. However, a large variety of fused-heterocyclic dyes containing a pseudo-aromatic ring in the rigid structure have shown to be incompatible with them. To approximate a solution within the ICT concept, we reported a novel ICT model called partially aromatized intramolecular charge transfer (PAICT). PAICT involves the generation of a CT state from an ICT that occurred within a pre-excited D–A fused-heterocyclic structure possessing a pseudo-aromatic or unstable aromatic ring as the acceptor moiety. The model was proposed from the multiple-emissive mesomeric D–A N 1 -aryl-2-(trifluoromethyl)­benzo­[b]­[1,8]­naphthyridin-4­(1H)-one, whose excited mesomeric states, which are defined by the aromatic and pseudo-aromatic forms of the pyrindin-4­(1H)-one ring, led to a common partial aromatized CT state upon excitation via PAICT. The latter was supported through theoretical calculations on the excited mesomeric states, one-dimensional (1D) and two-dimensional (2D) excitation–emission measurements in different solvents, and the detection of three excited states by lifetime measurements upon 370 nm excitation. The existence of mesomerism was supposed from: (i) two overlapping bands at 370–390 (or 400–420 nm) in UV–vis spectra, (ii) the direct interaction between the pyridinic nitrogen of one molecule and the carbonylic oxygen of the other found in the solid state and, (iii) the detection of three excited states by lifetime measurements. The PAICT opens new perspectives for interpreting the charge-transfer phenomenon in fused-heterocyclic dyes, in particular, those containing a pseudo-aromatic or unstable aromatic ring as an acceptor moiety.

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To identify new agents for the treatment of American cutaneous leishmaniasis, a series of eight 1,4-bis(substituted benzalhydrazino)phthalazines was evaluated against Leishmania braziliensis and Leishmania mexicana parasites. These compounds represent a disubstituted version of the 1-chloro-4-(monoaryl/heteroarylhydranizyl)phthalazine that exhibited a significant response against L. braziliensis according to our previous findings. Two disubstituted phthalazines 3b and 3f were identified as potential antileishmanial agents against L. braziliensis parasites, exhibiting a submicromolar IC 50 response of 2.37 and 7.90 µM on the promastigote form, and of 1.82 and 4.56 µM against intracellular amastigotes, respectively. In particular, compound 3b showed interesting responses against amastigote isolates from reference, glucantime-resistant and clinical human strains, which were by far superior to the biological response found for the glucantime drug. With regard to the toxicity results, both 3b and 3f exhibited moderate LD 50 values against murine macrophages (BMDM), with good selectivity indexes on promastigotes and intracellular amastigotes of L. braziliensis. A comparison of biological response was established between the monosubstituted and disubstituted versions of these benzalhydrazino-phthalazines. Easy synthetic procedure and significant response against amastigote strains including against resistant lines made compound 3b a potential candidate for further pharmacokinetic and in vivo experiments as antileishmanial agent, and as a platform for further structural optimization. Mechanism-of-action studies and molecular docking simulations discarded the inhibition of superoxide dismutase as possible mode of action.