Imidazole Dimer Research Articles

T-shaped CH···π and antiparallel π···π interactions of metronidazole benzoate and phenyl supporting paddle-wheel manganese(II) and zinc(II) carboxylate complexes: Structural, spectroscopic, and theoretical studies

The interaction and mixing of MnCl2·4H2O with 4-methylbenzoic acid (pMeBz) (1) or ZnSO4·7H2O with phenoxylacetic acid (HPOA) (2) in alkaline alcoholic solution at room temperature, in the presence of metronidazole benzoate afforded novel paddle-wheel complexes. The complexes have been characterized by single crystal Xray diffraction (SCXRD) and spectroscopic techniques (FT-IR, NIR-Vis-UV). Both complexes exhibit weak hydrogen bonds and π···π interactions, which impact the isolated molecule arrangement for optimal packing. The crystal packing of these complexes is dependent on π···π interactions. In the manganese complex, parallel and T-shaped benzene···imidazole stacking dominates, while the zinc complex utilizes antiparallel π···π interactions involving the metronidazole benzoate. A π-hole interaction, π(CC)···π*(CO), with a π(CC)···π*(CC) transfer primarily drives the benzoate dimers formation. An additional antiparallel imidazole···imidazole dimer contributes to this crystal assembly. These findings highlight these metal complexes' interplay of electronic structure, electrostatics, and noncovalent interactions. The insights gained from this study can pave the way for designing functional materials with targeted properties by tailoring ligands to exploit specific interactions.

Electronic Fingerprint of the Protonated Imidazole Dimer Probed by X-ray Absorption Spectroscopy.

Protons in low-barrier superstrong hydrogen bonds are typically delocalized between two electronegative atoms. Conventional methods to characterize such superstrong hydrogen bonds are vibrational spectroscopy and diffraction techniques. We introduce soft X-ray spectroscopy to uncover the electronic fingerprints for proton sharing in the protonated imidazole dimer, a prototypical building block enabling effective proton transport in biology and high-temperature fuel cells. Using nitrogen core excitations as a sensitive probe for the protonation status, we identify the X-ray signature of a shared proton in the solvated imidazole dimer in a combined experimental and theoretical approach. The degree of proton sharing is examined as a function of structural variations that modify the shape of the low-barrier potential in the superstrong hydrogen bond. We conclude by showing how the sensitivity to the quantum distribution of proton motion in the double-well potential is reflected in the spectral signature of the shared proton.

Fast photochromism of helicene-bridged imidazole dimers.

The unique optical and magnetic properties of organic biradicaloids on polycyclic aromatic hydrocarbons are of fundamental interest in the development of novel organic optoelectronic materials. Open-shell π-conjugated molecules with helicity have recently attracted a great deal of attention due to the magnetic-field-dependence and spin-selectivity arising from the combination of helical chirality and electron spins. However, the molecular design for helical biradicaloids is limited due to the thermal instability and high reactivity. Herein, we achieved fast photochromic reactions and reversible photo-generation of biradical species using helicene-bridged imidazole dimers. A [9]helicene-bridged imidazole dimer exhibits reversible photochromism upon UV light irradiation. The transient species produced reversibly by UV light irradiation exhibited ESR spectra with a fine structure characteristic of a triplet radical pair, indicating the reversible generation of the biradical. The half-life of the thermal recombination reaction of the biradical was estimated to be 29 ms at 298 K. Conversely, a substantial activation energy barrier was confirmed for the intramolecular recombination reaction in the [7]helicene-bridged imidazole dimer, attributed to the extended pitch length of [7]helicene. The temperature dependence of the thermal back reactions revealed that the [7]helicene and [9]helicene moieties functioned as 'soft' and 'hard' molecular bridges, respectively. These findings pave the way for future advances in the development of photoswitchable helical biradicaloids.

Bridged-Imidazole Dimer Exhibiting Three-State Negative Photochromism with a Single Photochromic Unit.

Photochromic molecules that can exhibit multiple states of photochromism in a single photochromic unit are considered more attractive than traditional bistable photochromic molecules because they can offer more versatility and control in photoresponsive systems. We have synthesized a negative photochromic 1-(1-naphthyl)pyrenyl-bridged imidazole dimer (NPy-ImD) that has three different isomers: a colorless isomer, 6MR, a blue-colored isomer, 5MR-B, and a red-colored isomer, 5MR-R. NPy-ImD can interconvert between these isomers via a short-lived transient biradical, BR, upon photoirradiation. 5MR-R is the most stable isomer, and the energy levels of 6MR, 5MR-B, and BR are relatively close to each other. The colored isomers 5MR-R and 5MR-B are photochemically isomerized to 6MR via the short-lived BR upon irradiation with blue light and red light, respectively. The absorption bands of 5MR-R and 5MR-B are well separated by more than 150 nm, with a small overlap, which means they can be selectively excited with different light sources, visible light for 5MR-R and NIR light for 5MR-B. The colorless isomer 6MR is formed from the short-lived BR through a kinetically controlled reaction. 6MR and 5MR-B can then be converted to the more stable isomer 5MR-R through a thermodynamically controlled reaction, which is facilitated by the thermally accessible intermediate, BR. Notably, 5MR-R photoisomerizes to 6MR when irradiated with CW-UV light, whereas it photoisomerizes to 5MR-B by a two-photon process when irradiated with nanosecond UV laser pulses.

Negative Photochromic 3-Phenylperylenyl-Bridged Imidazole Dimer Offering Quantitative and Selective Bidirectional Photoisomerization with Visible and Near-Infrared Light

Selective bidirectional photoisomerization reactions with high conversion ratios between stable and metastable isomers by irradiation of photochromic molecules with visible light of different wavelengths have been an important issue for many years. For negative photochromic molecules known so far, metastable isomers also absorb UV or visible light in the same region as stable isomers, making it difficult to selectively achieve the reverse reaction by visible-light irradiation. We have demonstrated that the absorption bands of the stable and metastable isomers of 3-phenylperylenyl-bridged imidazole dimer are largely separated by more than 140 nm and that almost quantitative and selective bidirectional photoconversion can be achieved by 660 and 460 nm light. Furthermore, the forward reaction can be achieved completely with near-infrared light of 785 nm.

Acceleration of the thermal back-reaction and the finding of a non-photochromic isomer for a negative photochromic binaphthyl-bridged imidazole dimer.

The development of visible or near-infrared (NIR) light-responsive fast photoswitchable molecules for the real-time, non-contact control of physical and chemical properties has received increased attention because of the non-invasive features to materials and biological tissues. We report a new molecular design to accelerate the thermal back-reaction of the negative photochromic binaphthyl-bridged imidazole dimer, BN-ImD. We also found that irradiation of the BN-ImD derivative with methyl groups on the bridging binaphthyl unit with visible light produced an unprecedented photoreaction product with a unique eight-membered ring structure. These observations provide fascinating clues for the future development of fast negative photochromic molecules.

Stepwise Photochromism of Bis(Imidazole Dimer) Bridged by a Sulfur Atom.

We report the development of the stepwise photochromic imidazole dimer bridged by a sulfur atom. The one-photon absorption leads to the generation of the colored biradical species, which rapidly recombines to the initial imidazole dimer following first-order reaction kinetics. The further photochemical reaction of the biradical species produces the long-lived colored species, which shows intermolecular dimerization.

In Silico Anticipation of Metabolic Pathways Extended to Organic Chemistry Reactions: A Case Study with Caffeine Alkaline Hydrolysis and The Origin of Camellimidazoles.

Camellimidazoles A-C were recently reported as natural substances in Keemun black tea. Although a "biosynthetic" route to these intriguing imidazole dimers was proposed from caffeine by the authors in this seminal report, we envisioned that a artefactual scenario, consisting of alkaline hydrolysis of caffeine and spontaneous cascade reactions with a methylene donor such as formaldehyde or methylene chloride, could also have led to their formation. To capture the diversity of molecules obtained under these conditions (i.e. alkaline treatment of caffeine/formaldehyde), an in silico MetWork-based pipeline was implemented, highlighting the sought-after camellimidazoles B and C. A wealth of further compounds were also tagged, notably comprising the herein newly described and unnatural camellimidazoles D-F that were subsequently confirmed as anticipated in silico upon extensive spectroscopic analyses. Likewise, camellimidazoles B and C could also be obtained using methylene chloride as an alternative methylene donor which may also have occurred in the initial phytochemical pipeline that implied this solvent. The current investigation emphasizes the fitness of MetWork tagging to extend the logic of in silico anticipation of metabolic pathways to organic chemistry reactions.

Gaussian process model of 51-dimensional potential energy surface for protonated imidazole dimer.

The goal of the present work is to obtain accurate potential energy surfaces (PESs) for high-dimensional molecular systems with a small number of ab initio calculations in a system-agnostic way. We use probabilistic modeling based on Gaussian processes (GPs). We illustrate that it is possible to build an accurate GP model of a 51-dimensional PES based on 5000 randomly distributed ab initio calculations with a global accuracy of <0.2 kcal/mol. Our approach uses GP models with composite kernels designed to enhance the Bayesian information content and represents the global PES as a sum of a full-dimensional GP and several GP models for molecular fragments of lower dimensionality. We demonstrate the potency of these algorithms by constructing the global PES for the protonated imidazole dimer, a molecular system with 19 atoms. We illustrate that GP models thus constructed can extrapolate the PES from low energies (<10 000 cm-1), yielding a PES at high energies (>20 000 cm-1). This opens the prospect for new applications of GPs, such as mapping out phase transitions by extrapolation or accelerating Bayesian optimization, for high-dimensional physics and chemistry problems with a restricted number of inputs, i.e., for high-dimensional problems where obtaining training data is very difficult.

Electric deflection of imidazole dimers and trimers in helium nanodroplets: Dipole moments, structure, and fragmentation.

Deuterated imidazole (IM) molecules, dimers, and trimers formed in liquid helium nanodroplets are studied by the electrostatic beam deflection method. Monitoring the deflection profile of (IM)D+ provides a direct way to establish that it is the primary product of the ionization-induced fragmentation both of (IM)2 and (IM)3. The magnitude of the deflection determines the electric dipole moments of the parent clusters: nearly 9 D for the dimer and 14.5 D for the trimer. These very large dipole values confirm theoretical predictions and derive from a polar chain bonding arrangement of the heterocyclic imidazole molecules.

Fast Photochromism of the Imidazole Dimers Bridged by Group 14 Atoms.

We developed fast photochromic imidazole dimers bridged by group 14 atoms. These compounds reversibly break the C-N bond to generate the colored open-ring biradical form. The colored form thermally reproduces the initial colorless form in the microsecond time scales. Furthermore, the color of the biradical can be easily controlled by the introduction of two different types of the imidazolyl radicals. These results give attractive insights for the further development of fast photochromic imidazole dimers.

Red or Near-Infrared Light Operating Negative Photochromism of a Binaphthyl-Bridged Imidazole Dimer.

The development of red or near-infrared light (NIR) switchable photochromic molecules is required for an efficient utilization of sunlight and regulation of biological activities. While the photosensitization of photochromic molecules to red or NIR light has been achieved by a two-photon absorption process, the development of a molecule itself having sensitivity to red or NIR light has been now a challenging study. Herein, we developed an efficient molecular design for realizing red or NIR-light-responsive negative photochromism based on binaphthyl-bridged imidazole dimers. The introduction of electron-donating substituents shows the red shift of the absorption band at the visible-light region because of the contribution of a charge-transfer transition. Especially, the introduction of a di(4-methoxyphenyl)amino group (TPAOMe) and a perylenyl group largely shifts the absorption edge of the stable colored form to 900 nm. In addition, because the absorption band of one of the derivatives substituted with TPAOMe covers the whole visible-light region, the colored form shows a neutral gray color. Upon red (660 nm) or NIR-light (790 nm) irradiation, we observed the negative photochromic reaction from the stable colored form to the metastable colorless form. Therefore, the substituted binaphthyl-bridged imidazole dimers constitute the attractive photoswitches within a biological window.

Exploration of imidazole and imidazopyridine dimers as anticancer agents: Design, synthesis, and structure-activity relationship study.

Dimerization of proteins/receptors plays a critical role in various cellular processes, including cell proliferation and differentiation. Therefore, targeting such dimeric proteins/receptors by dimeric small molecules could be a potential therapeutic approach to treating various diseases, including inflammation-associated diseases like cancer. A novel series of bis-imidazoles (13-18) and bis-imidazo[1,2-a]pyridines (19-28) were designed and synthesized from Schiff base dimers (1-12) for their anticancer activities. All the synthesized compounds were screened for anticancer activities against three cancer cell lines, including cervical (HeLa), breast (MDA-MB-231), and renal cancer (ACHN). From structure-activity relationship studies, imidazo[1,2-a]pyridines (19-28) showed remarkable cytotoxic activities, with compounds 19 and 24 showing the best inhibitory activities against all three cell lines. Especially, both 19 and 24 were very effective against the breast cancer cell line (19, GI50 = 0.43 µM; 24, GI50 = 0.3 µM), exceeding the activity of the control adriamycin (GI50 = 0.51 µM). The in vivo anticancer activity results of compounds 19 and 24 were comparable with those of the animals treated with the standard drug tamoxifen. Therefore, the dimeric imidazo[1,2-a]pyridine scaffold could serve as a potential lead for the development of novel anticancer agents.

Turn-On Mode Fluorescence Switch by Using Negative Photochromic Imidazole Dimer.

The development of fluorescence switchable molecules in several polar and apolar environments has been required for fluorescence imaging of nanostructures. Photochromic molecules are an important class for the reversible light-triggered fluorescence switching. Although many studies of fluorescence switching by using photochromic reactions have been reported, the report of photochromic molecules reversibly showing turn-on mode fluorescence switching has been limited in spite of their importance. Herein, we report the photoactivatable fluorescence based on negative photochromism, where the absorption spectrum of the compound after irradiation is blue-shifted relative to that before irradiation. We introduced naphthalimide units as a green fluorophore to the negative photochromic binaphthyl-bridged imidazole dimer. The fluorescence of the naphthalimide unit is efficiently quenched in the initial colored isomer (fluorescence quantum yield: Φfluo. = 0.01) by Förster resonance energy transfer. In contrast, the fluorescence quantum yield increases up to 0.75 in the transient isomer formed by the negative photochromic reaction. The fluorescence intensity thermally decreases with the thermal back reaction to form the original stable colored form. These results indicate that the negative photochromic molecules are suitable for turn-on mode fluorescence switches and will give an attractive insight for the development of reversible fluorescence switching molecules.

Fluorescence modulation by fast photochromism of a [2.2]paracyclophane-bridged imidazole dimer possessing a perylene bisimide moiety

We demonstrated the red-color fluorescence switching of a perylene bisimide (PBI) derivative by using a fast photochromic [2.2]paracyclophane-bridged imidazole dimer.

Theoretical investigation of the photochromic properties of [2.2]paracyclophane-bridged imidazole dimers and bis(imidazole) dimers

[2.2]paracyclophane-bridged imidazole dimers are excellent candidates to build fast photochromic devices with practical applications in full–colour holographic display. Herein, we propose an accurate, yet affordable, computational protocol relying on (TD-)DFT for investigating the structural, thermodynamical and optical properties of these systems, three properties of fundamental importance for their potential applications in fast light modulator devices. Within this theoretical framework, we provide an interpretation of the stepwise two-photon photochromic reaction observed for a symmetric [2.2]paracyclophane-bridged bis(imidazole dimer) and propose a new dissymmetric dimer with potential wavelength-dependent photoactivity.

Accelerating direct quantum dynamics using graphical processing units.

Methods using a swarm of Gaussian basis functions to represent the nuclear wavefunction are a very appealing way to solve the time-dependent Schrödinger equation (TDSE) as they avoid the conventional scaling bottleneck of grid-based methods and provide a grid-free trajectory representation of the dynamics understudy. When coupled with direct (on-the-fly) dynamics, these methods offer the ability to simulate quantum dynamics of larger systems in full nuclear configuration space and avoid the requirement of a priori fitting of a potential energy surface. During such simulations, it is often assumed that the limiting factor is the computational cost of the quantum chemistry calculations. To combat this, in the present paper the direct dynamics variational multi-configurational Gaussian (DD-vMCG) method is combined with electronic structure calculations accelerated by Graphical Processing Units (GPUs). For the systems studied, a protonated ammonia dimer and the imidazole dimer, it is shown that the cost of the term responsible for the quantum behaviour of the nuclear dynamics means that the computational time associated with the quantum chemistry quickly becomes a small part of the overall computational time. Using these simulations, an estimated scaling of the vMCG method, with respect to the number of Gaussian basis functions is reported. This can be used to identify when quantum chemistry is the limiting factor and when GPU acceleration will have a significant effect for both ground and excited state simulations.

Switching to Bright

Switching to Bright

Stepwise Two-Photon-Induced Fast Photoswitching via Electron Transfer in Higher Excited States of Photochromic Imidazole Dimer.

Stepwise two-photon excitations have been attracting much interest because of their much lower power thresholds compared with simultaneous two-photon processes and because some stepwise two-photon processes can be initiated by a weak incoherent excitation light source. Here we apply stepwise two-photon optical processes to the photochromic bridged imidazole dimer, whose solution instantly changes color upon UV irradiation and quickly reverts to the initial color thermally at room temperature. We synthesized a zinc tetraphenylporphyrin (ZnTPP)-substituted bridged imidazole dimer, and wide ranges of time-resolved spectroscopic studies revealed that a ZnTPP-linked bridged imidazole dimer shows efficient visible stepwise two-photon-induced photochromic reactions upon excitation at the porphyrin moiety. The fast photoswitching property combined with stepwise two-photon processes is important not only for the potential for novel photochromic materials that are sensitive to the incident light intensity but also for fundamental photochemistry using higher excited states.

Geometry of an Isolated Dimer of Imidazole Characterised by Rotational Spectroscopy and Ab Initio Calculations.

An isolated, gas-phase dimer of imidazole is generated through laser vaporisation of a solid rod containing a 1:1 mixture of imidazole and copper in the presence of an argon buffer gas undergoing supersonic expansion. The complex is characterised through broadband rotational spectroscopy and is shown to have a twisted, hydrogen-bonded geometry. Calculations at the CCSD(T)(F12*)/cc-pVDZ-F12 level of theory confirm this to be the lowest-energy conformer of the imidazole dimer. The distance between the respective centres of mass of the imidazole monomer subunits is determined to be 5.2751(1) Å, and the twist angle γ describing rotation of one monomer with respect to the other about a line connecting the centres of mass of the monomers is determined to be 87.9(4)°. Four out of six intermolecular parameters in the model geometry are precisely determined from the experimental rotational constants and are consistent with results calculated ab initio.