A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases.

In the field of rare and intractable diseases, new drug development is difficult and drug repositioning (DR) is a key method to improve this situation. In this study, we present a new method for finding DR candidates utilizing virtual screening, which integrates amino acid interaction mapping into scaffold-hopping (AI-AAM). At first, we used a spleen associated tyrosine kinase inhibitor as a reference to evaluate the technique, and succeeded in scaffold-hopping maintaining the pharmacological activity.

Unraveling the electronic structure of azolehemiporphyrazines: direct spectroscopic observation of magnetic dipole allowed nature of the lowest π-π* transition of 20π-electron porphyrinoids.

Hemiporphyrazines are a large family of phthalocyanine analogues in which two isoindoline units are replaced by other rings. Here we report unambiguous identification of 20π-electron structure of triazolehemiporphyrazines (1, 2) and thiazolehemiporphyrazine (3) by means of X-ray analysis, various spectroscopic methods, and density functional theory (DFT) calculations. The hemiporphyrazines were compared in detail with dibenzotetraazaporphyrin (4), a structurally related 18π-electron molecule.

Cyanine-like dyes with large bond-length alternation.

Herein, the synthesis and properties of alkyne-bridged carbocations, which are analogous in structure to cyanine dyes, are reported. An alkene-bridged dye, linked at the third position of the indole, was also synthesized as a reference compound. These new carbocations are stable under ambient conditions, allowing characterization by UV/Vis and NMR ((1)H and (13)C) spectroscopies.

[18]/[20]π hemiporphyrazine: a redox-switchable near-infrared dye.

An aromatic hemiporphyrazine with an 18π-electron structure has been synthesized by oxidizing 20π-electron 8,10,21,23-tetrahydroxy-28,30-dicarba-27H,29H-hemiporphyrazine with bulky aryl ether substituents. The aromatic nature of the oxidized form was characterized by means of various spectroscopic methods and single-crystal X-ray analysis, with the help of quantum-chemical calculations. The oxidized hemiporphyrazine exhibited an intense absorption at ~850 nm.

Design of polymethine dyes with large third-order optical nonlinearities and loss figures of merit.

All-optical switching applications require materials with large third-order nonlinearities and low nonlinear optical losses. We present a design approach that involves enhancing the real part of the third-order polarizability (gamma) of cyanine-like molecules through incorporation of polarizable chalcogen atoms into terminal groups, while controlling the molecular length to obtain favorable one- and two-photon absorption resonances that lead to suitably low optical loss and appreciable dispersion enhancement of the real part of gamma. We implemented this strategy in a soluble bis(selenopyrylium) heptamethine dye that exhibits a real part of gamma that is exceptionally large throughout the wavelength range used for telecommunications, and an imaginary part of gamma, a measure of nonlinear loss, that is smaller by two orders of magnitude.

Using end groups to tune the linear and nonlinear optical properties of bis(dioxaborine)-terminated polymethine dyes.

Six anionic pentamethine dyes with different 2,2-difluoro-4-aryl-1,3,2(2 H)-dioxaborin-6-yl termini were synthesized and isolated as tetra-n-octylammonium salts with a variety of aryl groups appended to increase conjugation beyond the dioxaborine termini. The increased conjugation was expected to decrease the energy of the lowest-lying excited state, and increase the transition dipole moment linking this state to the ground state, which would be anticipated to result in an increase in the real part of the third-order polarizability, Re(gamma). UV/Vis-NIR absorption spectroscopy indicates that the absorption maxima in DMSO vary from 691 to 761 nm, with the longest wavelength transitions observed for a derivative where the aryl group is 4-nitrophenyl.

Photophysical properties of an alkyne-bridged bis(zinc porphyrin)-perylene bis(dicarboximide) derivative.

We report the synthesis, electrochemistry, and photophysical properties of a new donor-acceptor-donor molecule in which the meso carbon atoms of two zinc porphyrin (POR) units are linked through ethynylene bridges to the 1,7-positions of a central perylene-3,4:9,10-bis(dicarboximide) (PDI). In contrast to previously studied systems incorporating POR and PDI groups, this alkyne-based derivative shows evidence of through-bond electronic coupling in the ground state; the new chromophore exhibits absorption features similar to those of its constituent parts as well as lower energy features (at wavelengths up to ca. 1000 nm), presumably arising from donor-acceptor interactions.

Synthesis and two-photon spectrum of a bis(porphyrin)-substituted squaraine.

A chromophore in which zinc porphyrin donors are linked through their meso positions by ethynyl bridges to a bis(indolinylidenemethyl) squaraine core has been synthesized using Sonogashira coupling. The chromophore exhibits a two-photon absorption spectrum characterized by a peak cross section of 11,000 GM and, more unusually, also exhibits a large cross section of >780 GM over a photon-wavelength window 750 nm in width.

A new class of cyanine-like dyes with large bond-length alternation.

Cyanines, which represent a class of charged chromophores with an odd number of pi-conjugated carbons, display unique electronic and optical properties attributed to the strong electronic delocalization and the absence of any significant carbon-carbon bond-length alternation (BLA) along their backbones. The flatness of the corresponding electronic potential makes cyanine dyes the compounds to which simple free-electron theory can be applied in the most relevant way. Recently, cations of porphyrin dimers linked by a pi-conjugated bridge with an odd number of carbons and presenting alternating single and triple bonds were shown to possess linear and nonlinear optical properties analogous to those of cyanines.

A spray-processable, low bandgap, and ambipolar donor-acceptor conjugated polymer.

Combining a strong donor, tris(dodecyloxy)phenyl)-dithieno[3,2-b:2',3'-d]pyrrole, with a strong acceptor, 4,8-dithien-2-yl-2lambda(4)delta(2)-benzo[1,2-c;4,5-c']bis[1,2,5]thiadiazole, has yielded the lowest bandgap, soluble, spray-processable polymer to date. The polymer has access to four different redox states and shows ambipolar behavior in OFETs. Multiple techniques, including transmission/absorption spectroscopy on SWCNTs and reflectance spectroscopy on gold were used to accurately estimate the optical bandgap at 0.

Electronic and vibronic contributions to two-photon absorption in donor-acceptor-donor squaraine chromophores.

Many squaraines have been observed to exhibit two-photon absorption at transition energies close to those of the lowest energy one-photon electronic transitions. Here, the electronic and vibronic contributions to these low-energy two-photon absorptions are elucidated by performing correlated quantum-chemical calculations on model chromophores that differ in their terminal donor groups (diarylaminothienyl, indolenylidenemethyl, dimethylaminopolyenyl, or 4-(dimethylamino)phenylpolyenyl). For squaraines with diarylaminothienyl and dimethylaminopolyenyl donors and for the longer examples of 4-(dimethylamino)phenylpolyenyl donors, the calculated energies of the lowest two-photon active states approach those of the lowest energy one-photon active (1B(u)) states.