Dipyrrolonaphthyridinedione - (still) a mysterious cross-conjugated chromophore.

Dipyrrolonaphthyridinediones (DPNDs) entered the chemical world in 2016. This cross-conjugated donor-acceptor skeleton can be prepared in two steps from commercially available reagents in overall yield ≈15-20% (5 mmol scale). DPNDs can be easily and regioselectively halogenated which opens an avenue to numerous derivatives as well as to π-expansion. Although certain synthetic limitations exist, the current derivatization possibilities provided impetus for numerous explorations that use DPNDs. Structural modifications enable bathochromic shift of the emission to deep-red region and reaching the optical brightness 30 000 M-1 cm-1. Intense absorption and strong emission of greenish-yellow light attracted the interest which eventually led to the discovery of their strong two-photon absorption, singlet fission in the crystalline phase and triplet sensitization. Dipyrrolonaphthyridinedione-based twistacenes broadened our knowledge on the influence of twisting angle on the fate of the molecule in the excited state. Collectively, these findings highlight the compatibility of DPNDs with various applications within organic optoelectronics.

Realization of nitroaromatic chromophores with intense two-photon brightness.

Strong fluorescence is a general feature of dipyrrolonaphthyridinediones bearing two nitrophenyl substituents. Methyl groups simultaneously being weakly electron-donating and inducing steric hindrance appear to be a key structural parameter that allows for significant emission enhancement, whereas Et2N groups cause fluorescence quenching. The magnitude of two-photon absorption increases if 4-nitrophenyl substituents are present while the contribution of Et2N groups is detrimental.

Machine Learning Based Prediction of Gamma Passing Rate for VMAT Radiotherapy Plans.

The use of machine learning algorithms (ML) in radiotherapy is becoming increasingly popular. More and more groups are trying to apply ML in predicting the so-called gamma passing rate (GPR). Our team has developed a customized approach of using ML algorithms to predict global GPR for electronic portal imaging device (EPID) verification for dose different 2% and distance to agreement 2 mm criteria for VMAT dynamic plans. Plans will pass if the GPR is greater than 98%. The algorithm was learned and tested on anonymized clinical data from 13 months which resulted in more than 3000 treatment plans. The obtained results of GPR prediction are very interesting. Average specificity of the algorithm based on an ensemble of 50 decision tree regressors is 91.6% for our criteria. As a result, we can reduce the verification process by 50%. The novel approach described by our team can offer a new insight into the application of ML and neural networks in GPR prediction and dosimetry.

Tuning the aromatic backbone twist in dipyrrolonaphthyridinediones.

This communication describes the photophysical behavior of three analogs of cyclophane bearing the dipyrrolonaphthyridinedione (DPND) core. In these molecules, intersystem crossing (ISC) can be successfully induced by distinct changes in the deviation from planarity within the DPND core, allowing at the same time the emission maximum to shift from the green to red region of the visible spectrum without any synthetic modifications of the chromophore structure. This finding may build the foundation for a new paradigm for inducing ISC-type transitions within other centrosymmetric and planar cross-conjugated chromophores.

Rhodaelectro-Catalyzed peri-Selective Direct Alkenylations with Weak O-Coordination Enabled by the Hydrogen Evolution Reaction (HER).

Direct C-H functionalizations by electrocatalysis is dominated by strongly coordinating N(sp2 )-directing groups. In sharp contrast, direct electrocatalytic transformations of weakly-coordinating phenols remain underdeveloped. Herein, electrooxidative peri C-H alkenylations of challenging 1-naphthols were achieved by versatile rhodium(III) catalysis via user-friendly constant current electrolysis. The rhodaelectrocatalysis employed readily-available alkenes and a protic reaction medium and features ample scope, good functional group tolerance and high site- and stereoselectivity. The strategy was successfully applied to high-value, nitrogen-containing heterocycles, thereby providing direct access to uncommon heterocyclic motifs based on the dihydropyranoquinoline skeleton.

Potent strategy towards strongly emissive nitroaromatics through a weakly electron-deficient core.

Nitroaromatics seldom fluoresce. The importance of electron-deficient (n-type) conjugates, however, has inspired a number of strategies for suppressing the emission-quenching effects of the strongly electron-withdrawing nitro group. Here, we demonstrate how such strategies yield fluorescent nitroaryl derivatives of dipyrrolonaphthyridinedione (DPND). Nitro groups near the DPND core quench its fluorescence. Conversely, nitro groups placed farther from the core allow some of the highest fluorescence quantum yields ever recorded for nitroaromatics. This strategy of preventing the known processes that compete with photoemission, however, leads to the emergence of unprecedented alternative mechanisms for fluorescence quenching, involving transitions to dark nπ* singlet states and aborted photochemistry. Forming nπ* triplet states from ππ* singlets is a classical pathway for fluorescence quenching. In nitro-DPNDs, however, these ππ* and nπ* excited states are both singlets, and they are common for nitroaryl conjugates. Understanding the excited-state dynamics of such nitroaromatics is crucial for designing strongly fluorescent electron-deficient conjugates.

An Efficient Method for the Programmed Synthesis of Multifunctional Diketopyrrolopyrroles.

A new, transformative methodology for the preparation of diketopyrrolopyrroles from aldehydes, primary amines, nitriles, and diethyl oxalacetate has been developed. It is now possible to prepare diketopyrrolopyrroles bearing an ordered arrangement of three different substituents from abundant and commercially available materials, allowing the independent regulation of all desired physicochemical properties. For the first time very electron-rich (carbazol-3-yl, dimethylaminophenyl, pyrrolo[3,2-b]pyrrolyl), and sterically hindered substituents (naphthalen-1-yl, quinolin-4-yl, acridin-9-yl, imidazo[1,5-a]pyridin-1-yl, 2-bromophenyl etc.) can be appended to the diketopyrrolopyrrole core by condensation of an appropriate nitrile with a pyrrolidin-2-one intermediate. Even greater synthetic possibilities are related to the fact that such demanding substituents as 4-dimethylaminophenyl, indol-3-yl, and 2-methoxyphenyl can be incorporated from aldehyde precursors, bypassing problems with the nitriles reactivity.

Synthetic Applications of Oxidative Aromatic Coupling-From Biphenols to Nanographenes.

Oxidative aromatic coupling occupies a fundamental place in the modern chemistry of aromatic compounds. It is a method of choice for the assembly of large and bewildering architectures. Considerable effort was also devoted to applications of the Scholl reaction for the synthesis of chiral biphenols and natural products. The ability to form biaryl linkages without any prefunctionalization provides an efficient pathway to many complex structures. Although the chemistry of this process is only now becoming fully understood, this reaction continues to both fascinate and challenge researchers. This is especially true for heterocoupling, that is, oxidative aromatic coupling with the chemoselective formation of a C-C bond between two different arenes. Analysis of the progress achieved in this field since 2013 reveals that many groups have contributed by pushing the boundary of structural possibilities, expanding into surface-assisted (cyclo)dehydrogenation, and developing new reagents.

From Dipyrrolonaphthyridinediones to Quinazolinoindolizinoindolizinoquinazolines.

The dipyrrolonaphthyridinedione (DPND) core can be readily converted into a series of acid-responsive quinazolinoindolizinoindolizinoquinazolines through a two-step route involving direct arylation followed by acid-catalyzed condensation. Unlike the majority of previously obtained DPNDs, these nonplanar dyes bearing eight fused rings are almost nonfluorescent, which is attributed to fast internal conversion relative to radiative decay and intersystem crossing.

Electron-Rich Dipyrrolonaphthyridinediones: Synthesis and Optical Properties.

This article describes the design rationale for highly electron-rich dipyrrolonaphthyridinedione (DPND) derivatives bearing substituted amino groups at the 3 and 9 positions, which exhibit absorption in the red and emission in the red/NIR region of the spectrum. These novel dyes are easily synthesized through a two-step protocol consisting of bromination of the DPND molecule followed by Buchwald-Hartwig amination. We demonstrated that the diamino-dipyrrolonaphthyridinediones have high ionization energies (∼4.7 eV) and that the spectroelectrochemical properties can be rationally tuned by altering the nature of the peripheral substituted amino groups. All amino-DPNDs exhibit solvatofluorochromism, which has not been previously reported for dyes possessing this core. Theoretical calculations reveal that in all cases, the strongest absorption is exhibited by the S1 states which clearly correlate with the HOMO-LUMO orbital transition. As all higher states have lower oscillator strengths, it is clear that fluorescence is completely dominated by the excitation/deexcitation sequence S0 → S1, S1 → S0 and that there are no contributions to the fluorescence from excitations to higher states.

Tetraphenylethylenepyrrolo[3,2- b]pyrrole Hybrids as Solid-State Emitters: The Role of Substitution Pattern.

Two hybrid dyes possessing tetraphenylethylene moieties weakly conjugated with a pyrrolo[3,2- b]pyrrole core have been synthesized. Both dyes display a weak emission in solution, however, in the solid state a ∼100-fold increase in the fluorescence quantum yield is observed. The position of the molecular rotors about the core greatly influences the photophysical characteristics. The variances in emission properties were assigned to entirely different changes in dihedral angles upon excitation, which in turn have substantial effects on radiative rate constants, allowed transitions, and HOMO/LUMO distribution.

Direct Arylation of Dipyrrolonaphthyridinediones Leads to Red-Emitting Dyes with Conformational Freedom.

A series of bis-aryl dipyrrolonaphthyridinediones (DPNDs) with various substitution patterns have been designed and synthesized by direct arylation. This reaction occurs regioselectively at positions 3 and 9, which gives a straightforward entry to unique dyes that absorb in the red/far-red region and emit in the far-red/NIR region. The photophysical properties (absorption and fluorescence wavelength) can be controlled by altering the steric hindrance and electronic character of the peripheral aryl group. The fluorescence quantum yields are moderate in the majority of cases and almost independent of changes in the solvent polarity. DPNDs bearing substituents at the ortho position that prevent free rotation of the phenyl ring emit stronger fluorescence relative to the unhindered para analogues and, at the same time their absorption and emission bands are blueshifted. We have used computational methods to explain why electron-donating substituents have significantly stronger effects than electron-withdrawing substituents on the optical properties by invoking the electron-accepting character of the DPND. Electrochemical measurements revealed that the HOMO and LUMO, as well as the electrochemical band gap, also depend strongly on the electronic character of the peripheral group.

π-Expanded Dipyrrolonaphthyridinediones with Large Two-Photon Absorption Cross-Section Values.

A synthetic entry to novel dyes based on the dipyrrolonaphthyridinedione core was developed via the Heck reaction. These weakly fluorescent compounds bearing double bond linkages between the core and the peripheral units absorbed strongly in the far-red/NIR region and possessed large values of two-photon absorption (TPA) cross-sections (up to 5180 GM). Additionally, analogous dyes bearing triple bond linkages were also efficient TPA materials with relatively large two-photon absorption cross-sections (up to 2840 GM) as well as two-photon brightness (up to 1450 GM). The centrosymmetric nature of both of these families of dyes is responsible for the location of the maxima of two-photon absorption being at much higher energy than the ones corresponding to the double wavelength of the lowest-energy one-photon absorption. Theoretical calculations clarified that the enhancement of the TPA by the peripheral substitutions arose through different mechanisms depending on either the electron-donating or electron-withdrawing ability of a given substituent to the ambipolar core. The change in the electron distribution of HOMO and HOMO-1 by the push-pull effect was found to govern the strength of the lowest-energy TPA-allowed transition. Importantly, compounds from both series possessed a beneficial ratio of σ2/MW (1.6-9.8 GM/g).

Recent advances in the synthesis of indolizines and their π-expanded analogues.

Indolizine (pyrrolo[1,2-a]pyridine) is one of the five isomers of indole and it serves as a precursor for widespread indolizidine alkaloids. The straightforward synthesis of indolizines based on classical methodologies such as Scholtz or Chichibabin reactions has overshadowed numerous new strategies that have been revealed especially within the last ten years. The desire to achieve substitution patterns which were hard to build sparked the discovery of completely new pathways, e.g. transition metal-catalyzed reactions and approaches based on oxidative coupling. In this review, selected strategies toward indolizines published since 2005 are briefly summarized, commented upon, compared, and illustrated. The literature discussed here involves reactions based on either pyridine or pyrrole scaffolds, as well as selected methodologies leading to π-expanded indolizines.

V-shaped bis-coumarins: synthesis and optical properties.

A highly efficient procedure for the synthesis of bis-coumarins fused at the pyranone ring has been developed. The electron-rich phenols reacted with esters of coumarin-3-carboxylic acids, leading to substituted chromeno[3,4-c]chromene-6,7-diones. The reaction is catalyzed by both Lewis acids and 4-dimethylaminopyridine. The most probable mechanistic pathway involves Lewis acid catalyzed or DMAP catalyzed transesterification, followed by intramolecular conjugate addition of α,ß-unsaturated esters to phenols and subsequent oxidation of the initially formed intermediate. The reaction is compatible with various functionalities such as NO2, Br, and OMe. Not only benzene derivatives but also dihydroxynaphthalenes are reactive in this reaction, and the structure of the product can be controlled by adjusting the reaction conditions. Furthermore, a double addition is possible, leading to a horseshoe-shaped system comprised of seven conjugated rings. Compounds with four structurally unique skeletons have been obtained and have been shown to strongly absorb in the violet, blue, and/or green regions of the visible spectrum. Most of them display strong greenish yellow fluorescence, which can be modulated by both structural changes and the character of the solvents. Again, introduction of an electron-donating group in the chromeno[3,4-c]chromene-6,7-diones caused a significant red shift in both the absorption and emission maxima, and the effect became especially noteworthy in the case of amino substituents.

Excited state intramolecular proton transfer in π-expanded phenazine-derived phenols.

Two previously inaccessible analogs of 10-hydroxybenzo[h]quinoline were prepared via a straightforward strategy comprising the formation of π-expanded phenazines skeleton followed by C-H acetoxylation at position 10. Two bis-phenols possessing C2 and D2 symmetry were obtained in yields of 52% and 15%, respectively. The occurrence of excited state intramolecular proton transfer (ESIPT) was detected in all cases because steady state emission was observed only from the excited keto-tautomer. Additionally, a short-lived, ∼0.1 ps, emission decay was resolved by the femtosecond up-conversion technique at the blue side of the keto-tautomer emission band, 610 nm, and was attributed to the ESIPT, i.e., conversion from enol to keto tautomer. In comparison with the corresponding 10-hydroxybenzo[h]quinoline emissions, the emission spectrum of the π-expanded phenazine analogues were weaker but displayed a characteristic bathochromically shift into NIR region. These phenazine analogues constitute one of largest heterocycles for which ESIPT was unambiguously detected.