C(sp3)-H cyclizations of 2-(2-vinyl)phenoxy-tert-anilines.

1,5-hydride transfer-triggered cyclization reactions offering a robust method for C(sp3)-C(sp3) coupling and the synthesis of e.g. tetrahydroquinolines have been thoroughly investigated in the literature. Catalysts allowing milder reaction conditions or the development of enantioselective processes were important recent contributions to the field, as well as the studies on subtrates with oxygen or sulfur heteroatoms (besides the originally described nitrogen heterocycles). In a series of studies, we focused on expanded, higher order H-transfers/cyclizations by positioning the interacting substituents on distanced rings. Cyclizations of appropriately functionalized biaryl and fused bicyclic systems led to 7-9 membered rings. In the frame of this research, we set out to study the feasibility of the cyclization and the factors affecting it by in silico methods. The conclusions drawn from computational studies were complemented by cyclization screens on 2-(2-vinyl)phenoxy-tert-anilines and their CH2-expanded analogues, the results of which are presented here. Besides isolating the expected oxazonine products in several cases, we also observed a unique dimer formation, leading to an interesting 5-6-5 ring system.

Excited state iminium form can explain the unexpected solvatochromic behavior of symmetric 1,5- and 1,8-diaminonaphthalenes.

A new model, based on the presence of the excited state iminium ion (Ar = NH2+), is proposed to interpret the solvatochromic behavior of symmetric 1,5- and 1,8-diaminonaphtahelenes (DANs) in aprotic to protic media. The importance of using explicit solvent models during DFT calculations in protic solvents to find the proper excited structure for symmetric molecules is also highlighted.

Effective synthesis, development and application of a highly fluorescent cyanine dye for antibody conjugation and microscopy imaging.

An asymmetric cyanine-type fluorescent dye was designed and synthesized via a versatile, multi-step process, aiming to conjugate with an Her2+ receptor specific antibody by an azide-alkyne click reaction. The aromaticity and the excitation and relaxation energetics of the fluorophore were characterized by computational methods. The synthesized dye exhibited excellent fluorescence properties for confocal microscopy, offering efficient applicability in in vitro imaging due to its merits such as a high molar absorption coefficient (36 816 M-1 cm-1), excellent brightness, optimal wavelength (627 nm), larger Stokes shift (26 nm) and appropriate photostability compared to cyanines. The conjugated cyanine-trastuzumab was constructed via an effective, metal-free, strain-promoted azide-alkyne click reaction leading to a regulated number of dyes being conjugated. This novel cyanine-labelled antibody was successfully applied for in vitro confocal imaging and flow cytometry of Her2+ tumor cells.

Preparation and Optical Study of 1-Formamido-5-Isocyanonaphthalene, the Hydrolysis Product of the Potent Antifungal 1,5-Diisocyanonaphthalene.

Aromatic isocyanides have gained a lot of attention lately as promising antifungal and anticancer drugs, as well as high-performance fluorescent analytical probes for the detection of toxic metals, such as mercury, even in vivo. Since this topic is relatively new and aromatic isocyanides possess unique photophysical properties, the understanding of structure-behavior relationships and the preparation of novel potentially biologically active derivatives are of paramount importance. Here, we report the photophysical characterization of 1,5-diisocyanonaphthalene (DIN) backed by quantum chemical calculations. It was discovered that DIN undergoes hydrolysis in certain solvents in the presence of oxonium ions. By the careful control of the reaction conditions for the first time, the nonsymmetric product 1-formamido-5-isocyanonaphthalene (ICNF) could be prepared. Contrary to expectations, the monoformamido derivative showed a significant solvatochromic behavior with a ~50 nm range from hexane to water. This behavior was explained by the enhanced H-bond-forming ability of the formamide group. The significance of the hydrolysis reaction is that the isocyano group is converted to formamide in living organisms. Therefore, ICNF could be a potential drug (for example, antifungal) and the reaction can be used as a model for the preparation of other nonsymmetric formamido-isocyanoarenes. In contrast to its relative 1-amino-5-iscyanonaphthalene (ICAN), ICNF is highly fluorescent in water, enabling the development of a fluorescent turnoff probe.