Enhancing the Potential of Fused Heterocycle-Based Triarylhydrazone Photoswitches.

Triarylhydrazones represent an attractive class of photochromic compounds offering many interesting features including high molar absorptivity, good addressability, and extraordinary thermal stability. In addition, unlike most other hydrazone-based photoswitches, they effectively absorb light above 365 nm. However, previously prepared triaryhydrazones suffer from low quantum yields of the Z→E photoisomerization. Here, we have designed a new subclass of naphthoyl-benzothiazole hydrazones that balance the most beneficial features of previously reported naphthoyl-quinoline and benzoyl-pyridine triarylhydrazones. These preserve the attractive absorption characteristics, exhibit higher thermal stability of the metastable form than the former and enhance the rate of the Z→E photoisomerization compared to the later, as a result of the weakening of the intramolecular hydrogen bonding between the hydrazone hydrogen and the benzothiazole moiety. Introducing the benzothiazole motif extends the tunability of the photochromic behaviour of hydrazone-based switches.

Enhancing the Potential of Fused Heterocycle-Based Triarylhydrazone Photoswitches.

Invited for the cover of this issue are Marek Cigán, Anna M. Grabarz and co-workers. The image depicts how a non-expert might imagine a "molecular photoswitch". Read the full text of the article at 10.1002/chem.202303509.

Rigidized 3-aminocoumarins as fluorescent probes for strongly acidic environments and rapid yeast vacuolar lumen staining: mechanism and application.

Coumarins remain one of the most important groups of fluorescent bio-probes, thanks to their high quantum yields, moderate photostability, efficient cell permeation and low (cyto)toxicity. Herein, we introduce new 3-aminocoumarins as turn-on pH probes under strongly acidic conditions and for indicators capable of significantly improving yeast vacuolar lumen staining compared to the commercial CMAC derivatives. We present the details of the on-off switching mechanism revealed by the TD-DFT and ab initio calculations complemented by a Franck-Condon analysis of the probes' emission profiles.

Mechanochemical Conversion of Aromatic Amines to Aryl Trifluoromethyl Ethers.

Increased interest in the trifluoromethoxy group in organic synthesis and medicinal chemistry has induced a demand for new, selective, general, and faster methods applicable to natural products and highly functionalized compounds at a later stage of hit-to-lead campaigns. Applying pyrylium tetrafluoroborate, we have developed a mechanochemical protocol to selectively substitute the aromatic amino group with the OCF3 functionality. The scope of our method includes 31 examples of ring-substituted anilines, including amides and sulfonamides. Expected SNAr products were obtained in excellent yields. The presented concise method opens a pathway to new chemical spaces for the pharmaceutical industry.

Mechanistic Insights into the Photoisomerization of N,N'-Disubstituted Indigos.

N,N'-disubstituted indigos are photoswitchable molecules that have recently caught the attention due to their addressability by red-light. When alkyl and aryl groups are utilized as the N-substituents, the thermal half-lives of Z isomers can be tuned independently while maintaining the advantageous red-shifted absorption spectra. To utilize these molecules in real-world applications, it is of immense importance to understand how their molecular structures as well as the environment influence their switching properties. To this end, we probed their photoisomerization mechanism by carrying out photophysical and computational studies in solvents of different polarities. The fluorescence and transient absorption experiments suggest for more polar excited and transition states, which explains the bathochromic shifts of absorption spectra and shorter thermal half-lives. On the other hand, the quantum chemical calculations reveal that in contrast to N-carbonyl groups, N-alkyl and N-aryl substituents are not strongly conjugated with the indigo chromophore and can thus serve as a tool for tuning the thermal stability of Z isomers. Both approaches are combined to provide in-depth understandings of how indigos undergo photoswitching as well as how they are influenced by N-substituent and the chemical surroundings. These mechanistic insights will serve as guiding principles for designing molecules eyeing broader applications.

Unsymmetrical benzothiazole-based dithienylethene photoswitches.

Herein, we investigate the structure-property relationships in a new series of benzothiazole based unsymmetrical hexafluorocyclopentene dithienylethenes (DTEs) and compare the results with the known facts for symmetric diarylethenes (DAEs). We reveal high photocyclization efficiency resulting from a significant shift of ground state equilibrium to the antiparallel conformation and a barrierless excited state pathway to conical intersection, which remains unperturbed even in polar solvents for most of the prepared DTEs. Furthermore, we uncover that the rate of back thermal cycloreversion correlates clearly more with the central C-C bond-length in the transition state than with the central C-C bond-length in the ground state of the cyclic form. Finally, our detailed vibrational spectral analysis of studied DTEs points out significant changes in Raman and infrared spectra during photoswitching cycles which pave the way for a non-destructive readout of stored information.

Design of High-Performance Pyridine/Quinoline Hydrazone Photoswitches.

The design of P-type photoswitches with thermal stability of the metastable form of hundreds of years that would efficiently transform using excitation wavelengths above 350 nm remains a challenge in the field of photochromism. In this regard, we designed and synthesized an extended set of 13 pyridine/quinoline hydrazones and systematically investigated the structure-property relationships, defining their kinetic and photoswitching parameters. We show that the operational wavelengths of the pyridine hydrazone structural motif can be effectively shifted toward the visible region without simultaneous loss of their high thermal stability. Furthermore, we characterized the ground-state and excited-state potential energy surfaces with quantum-chemical calculations and ultrafast transient absorption spectroscopy, which allowed us to rationalize both the thermal and photochemical reaction mechanisms of the designed hydrazones. Whereas introducing an electron-withdrawing pyridyl moiety in benzoylpyridine hydrazones leads to thermal stabilities exceeding 200 years, extended π-conjugation in naphthoylquinoline hydrazones pushes the absorption maxima toward the visible spectral region. In either case, the compounds retain highly efficient photoswitching characteristics. Our findings open a route to the rational design of a new family of hydrazone-based P-type photoswitches with high application potential in photonics or photopharmacology.

Highly Cooperative Photoswitching in Dihydropyrene Dimers.

We present a strategy to achieve highly cooperative photoswitching, where the initial switching event greatly facilitates subsequent switching of the neighboring unit. By linking donor/acceptor substituted dihydropyrenes via suitable π-conjugated bridges, the quantum yield of the second photochemical ring-opening process could be enhanced by more than two orders of magnitude as compared to the first ring-opening. As a result, the intermediate mixed switching state is not detected during photoisomerization although it is formed during the thermal back reaction. Comparing the switching behavior of various dimers, both experimentally and computationally, helped to unravel the crucial role of the bridging moiety connecting both photochromic units. The presented dihydropyrene dimer serves as model system for longer cooperative switching chains, which, in principle, should enable efficient and directional transfer of information along a molecularly defined path. Moreover, our concept allows to enhance the photosensitivity in oligomeric and polymeric systems and materials thereof.

General Principles for the Design of Visible-Light-Responsive Photoswitches: Tetra-ortho-Chloro-Azobenzenes.

Molecular photoswitches enable reversible external control of biological systems, nanomachines, and smart materials. Their development is driven by the need for low energy (green-red-NIR) light switching, to allow non-invasive operation with deep tissue penetration. The lack of clear design principles for the adaptation and optimization of such systems limits further applications. Here we provide a design rulebook for tetra-ortho-chloroazobenzenes, an emerging class of visible-light-responsive photochromes, by elucidating the role that substituents play in defining their key characteristics: absorption spectra, band overlap, photoswitching efficiencies, and half-lives of the unstable cis isomers. This is achieved through joint photochemical and theoretical analyses of a representative library of molecules featuring substituents of varying electronic nature. A set of guidelines is presented that enables tuning of properties to the desired application through informed photochrome engineering.

Observation of Collective Photoswitching in Free-Standing TATA-Based Azobenzenes on Au(111).

Light-induced transitions between the trans and cis isomer of triazatriangulenium-based azobenzene derivatives on Au(111) surfaces were observed directly by scanning tunneling microscopy, allowing atomic-scale studies of the photoisomerization kinetics. Although the azobenzene units in these adlayers are free-standing and spaced at uniform distances of 1.26 nm, their photoswitching depends on the isomeric state of the surrounding molecules and, specifically, is accelerated by neighboring cis isomers. These collective effects are supported by ab initio calculations indicating that the electronic excitation preferably localizes on the n-π* state of trans isomers with neighboring cis azobenzenes.

Excited state intramolecular proton transfer in julolidine derivatives: an ab initio study.

We have studied, using ab initio tools, a series of recently prepared fluorescent julolidine derivatives, undergoing Excited State Intramolecular Proton Transfer (ESIPT). We show that the computed free energy change in the excited state (ΔGES) can be used to predict the preference for enol, keto, or dual emission. Indeed, two julolidine molecules experimentally show dual emission, consistent with our finding of a small ΔGES. In agreement with experimental outcomes the complexation between the ESIPT centre and BF2 increases the rigidity of the fluorophore and greatly facilitates emission at energies close to the original enol (E*) fluorescence band. The protonation of the imino group also suppresses ESIPT and sole E* emission is obtained. We disclose that chemical substitution can significantly tune the radiationless deactivation of the enol related to the C[double bond, length as m-dash]N bond rotation of the ESIPT centre. While there is a significant barrier for the experimentally studied compounds we have found a strong correlation between the barrier height and the electron donating strength of the phenyl substituent. Strong donors such as amines facilitate the barrierless non-radiative decay from E* back to the ground state, while weak electron donors make the barrier sufficiently high to allow ESIPT. Strong electron accepting groups such as -NO2 further increase this barrier. This work therefore illustrates the fine interplay necessary to design dual emitters.

Efficient Light-Induced pKa †Modulation Coupled to Base-Catalyzed Photochromism.

Photoswitchable acid-base pairs, whose pKa values can be reversibly altered, are attractive molecular tools to control chemical and biological processes with light. A significant, light-induced pKa change of three units in aqueous medium has been realized for two thermally stable states, which can be interconverted using UV and green light. The light-induced pKa modulation is based on incorporating a 3-H-thiazol-2-one moiety into the framework of a diarylethene photoswitch, which loses the heteroaromatic stabilization of the negatively charged conjugate base upon photochemical ring closure, and hence becomes significantly less acidic. In addition, the efficiency of the photoreactions is drastically increased in the deprotonated state, giving rise to catalytically enhanced photochromism. It appears that protonation has a significant influence on the shape of the ground- and excited-state potential energy surfaces, as indicated by quantum-chemical calculations.

Arylazoindazole Photoswitches: Facile Synthesis and Functionalization via SNAr Substitution.

A straightforward synthetic route to arylazoindazoles via nucleophilic aromatic substitution is presented. Upon deprotonation of the NH group, a C6F5-substituted formazan undergoes facile cyclization as a result of intermolecular nucleophilic substitution (SNAr). This new class of azo photoswitches containing an indazole five-membered heterocycle shows photochemical isomerization with high fatigue resistance. In addition, the Z-isomers have long thermal half-lives in the dark of up to several days at room temperature. The fluorinated indazole group offers a handle for further functionalization and tuning of its properties, as it is shown to be susceptible to a subsequent, highly selective nucleophilic displacement reaction.

Exploring the Solvatochromism of Betaine†30 with Ab Initio Tools: From Accurate Gas-Phase Calculations to Implicit and Explicit Solvation Models.

Betaine 30 is known for the extraordinary solvatochromism of its visible absorption band that goes from λ=882 nm in tetrachloromethane to λ=453 nm in water (Δλ=-429 nm). This large blueshift partly originates from a dramatic decrease of the dipole moment upon excitation. Despite several decades of research, experimental works still disagree on the exact value of the excess dipole moment, the orientation of the dipole moment of the excited-state, the role and amplitude of the change of the polarisability upon excitation as well as on the gas-phase excitation energy. In this work, we present an in-depth theoretical investigation. First, we carefully tested several levels of theory on the model system and next calculated the electric properties of betaine 30 at the CC2 level. Our best estimates are Δµ=-7 D for the excess dipole moment, that is, a significant decrease but no change of direction, a Δα value of -120 a.u. and a gas-phase vertical excitation energy of 1.127 eV. The implicit solvation models are able to reproduce the experimental trends, with large correlation coefficients for non-hydrogen-bond-donating solvents, the smallest root-mean-square deviation error being reached with the vertical excitation model (VEM). The explicit effective fragment potential method combined with time-dependent density functional theory (TD-DFT) in a QM/MM framework provides accurate estimates for hydrogen-bond-donating solvents, whereas the addition of a dispersion correction is needed to restore the correct solvatochromic direction in tetrachloromethane.

On the Fine-Tuning of the Excited-State Intramolecular Proton Transfer (ESIPT) Process in 2-(2'-Hydroxybenzofuran)benzazole (HBBX) Dyes.

Herein, a full investigation of the optical properties and first-principles calculations of a large series of original 2-(2'-hydroxybenzofuran)benzazole (HBBX) dyes is described. The electronic substitution on the π-conjugated core of the fluorophores and the nature of the heteroatom (O, S, N) was varied extensively to assess the necessary parameters to trigger a partial frustration of the excited-state intramolecular proton transfer (ESIPT) process, which results in the emission of both tautomers, that is, enol and keto (E* and K*). The optical properties, studied in solution and in the solid state, revealed the appearance of either an intense single K* or a dual E*/K* emission; a feature that is highly dependent on the electronic substitution (donating or accepting), the heteroelement, and the close environment. Subtle modifications of these parameters allowed the establishment of structure-property relationships that were successfully rationalized by first-principles calculations. In particular, the E*/K* emission intensity ratio was shown to be directly related to the free energies of the two emissive tautomers in the excited state.

Calculations of n→π* Transition Energies: Comparisons Between TD-DFT, ADC, CC, CASPT2, and BSE/GW Descriptions.

Using a large panel of theoretical approaches, namely, CC2, CCSD, CCSDR(3), CC3, ADC(2), ADC(3), CASPT2, time-dependent density functional theory (TD-DFT), and BSE/evGW, the two latter combined with different exchange-correlation functionals, we investigate the lowest singlet transition in 23 n→π* compounds based on the nitroso, thiocarbonyl, carbonyl, and diazo chromophores. First, for 16 small derivatives we compare the transition energies provided by the different wave function approaches to define theoretical best estimates. For this set, it surprisingly turned out that ADC(2) offers a better match with CC3 than ADC(3). Next, we use 10 functionals belonging to the "LYP" and "M06" families and compare the TD-DFT and the BSE/evGW descriptions. The BSE/evGW results are less sensitive than their TD-DFT counterparts to the selected functional, especially in the M06 series. Nevertheless, BSE/evGW delivers larger errors than TD-CAM-B3LYP, which provides extremely accurate results in the present case, especially when the Tamm-Dancoff approximation is applied. In addition, we show that, among the different starting points for BSE/evGW calculations, M06-2X eigenstates stand as the most appropriate. Finally, we confirm that the trends observed on the small compounds pertain in larger molecules.

Synthesis and Photophysical Properties of Novel Donor-Acceptor N-(Pyridin-2-yl)-Substituted Benzo(thio)amides and Their Difluoroboranyl Derivatives.

The unprecedented N-pyridin-2-yl substituted benzo(thio)amides were prepared and subsequently converted into the cyclic difluoroboranyl (BF2) derivatives. Mass spectrometry, multinuclear NMR, IR, and elemental analysis confirmed the structure of these compounds. UV/vis and fluorescence spectroscopy as well as first-principle calculations were used to study their properties. For the first time, the influence of both the O/S replacement and presence/absence of the BF2 moiety on the photophysical properties of compounds exhibiting charge transfer properties were examined experimentally and theoretically. We show that the sulfur-containing compound has a much smaller emission quantum yield than its oxygen counterpart. The fluorescence quantum yield is much higher upon formation of the difluoroboranyl complex.

Critical analysis of spectral solvent shifts calculated by the contemporary PCM approaches of a representative series of charge-transfer complexes between tetracyanoethylene and methylated benzenes.

Applications of contemporary polarisable continuum model (PCM) quantum chemical approaches to account for the solvent shifts of UV-Vis absorption charge transfer (CT) transitions in electron donor-acceptor (EDA) complexes (as well as to account for their stability and other properties in solvents) have been rather rare until now. In this study, we systematically applied different - mainly state-specific - PCM approaches to examine excited state properties, namely, solvatochromic excitation energy shifts in a series of EDA complexes of a tetracyanoethylene (TCNE) acceptor with methyl substituted benzenes with different degrees of methylation N (NMB). For these complexes, representative and reliable experimental data exist both for the gas phase and in solution (dichloromethane). We have found that the linear response (LR) solvent shifts are too small compared to the experimental values, while self-consistent SS approaches give values that are too large. The best agreement with experimental values was obtained by corrected LR (cLR). The transition energies were calculated by means of TD-DFT methodology with PBE0, CAM-B3LYP and M06-2X functionals as well as the wave function CC2 method for the gas phase, and the PCM solvent shifts were added to account for the solvent effects. The best results for transition energies in solvents were obtained using the CC2 method complemented by CAM-B3LYP/cLR for the gas phase transition energy red solvent shift, while all three TD-DFT approaches used gave insufficient values (ca. 50%) of the slope of the dependence of the transition energies on N compared to experimental values.

Direct and indirect effects of dispersion interactions on the electric properties of weakly bound complexes.

Direct (electronic) and indirect (geometrical) modifications of the molecular properties of weakly interacting complexes between the push-pull p-aminobenzoic acid (pABA) molecule and the nonpolar benzene (Bz) have been studied with a large panel of wave function (WF) and density functional theory (DFT) based methods using carefully selected atomic basis sets. For pABA, both the canonical (pABA-c) and zwitterionic (pABA-z) forms have been investigated. Owing to strongly distinct charge distributions, the two forms of pABA enable us to mimic different interaction modes with Bz. In this work, we assessed the performances of dispersion-corrected DFT methods, as well as of long-range corrected exchange-correlation functionals. It follows from the SAPT analysis that both the structure and the interaction energy of the first complex (pABA-c···Bz) is mainly controlled by dispersion interactions whereas, in the second complex (pABA-z···Bz), electrostatic and induction forces play also an important role. Our results suggest that the (non)linear electric properties of push-pull and zwitterionic molecules can be significantly reduced by the presence of a nonpolar compound. We also show that even for a complex with stability strongly determined by dispersion forces, the direct dispersion contributions to its electric properties can be small. Nevertheless, the intersystem distance is influenced by dispersion forces, which, in turn indirectly tune the induced properties. The zwitterionic derivative appears to be more challenging in the context of molecular properties.

Full cLR-PCM calculations of the solvatochromic effects on emission energies.

We compare the solvatochromic shifts measured experimentally and obtained theoretically for the emission of several substitued fluorophores (indole, benzofurazan, naphthalimide…). Our theoretical protocol relies on time-dependent density functional theory and uses several variations of the polarisable continuum model. In particular, we compare the merits of the linear-response and the corrected linear response approaches, the latter being used for both energetic and structural calculations. It turns out that performing fully-consistent corrected linear response calculations yields the smallest mean signed and absolute errors for the solvatochromic shifts, although optimizing the excited-state structures at the linear-response level only induces limited increase of the average deviations. In contrast, for auxochromic effects, the average errors provided by the two solvation models are very similar.