Anion Receptors Research Articles

Transmembrane Transport of Bicarbonate by Anion Receptors.

The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by natural proteins. Transport of bicarbonate is important for crucial biological functions such as respiration and digestion. Despite this biological relevance, bicarbonate transport has not been as widely studied as chloride transport. Herein we present an overview of the synthetic receptors that have been studied as bicarbonate transporters, together with the different assays used to perform transport studies in large unilamellar vesicles. We highlight the most active transporters and comment on the nature of the functional groups present in active and inactive compounds. We also address recent mechanistic studies that have revealed different processes that can lead to net transport of bicarbonate, as well as studies reported in cells and tissues, and comment on the key challenges for the further development of bicarbonate transporters.

Unfurling Anion-π Interactions Involving Graphynes.

Ever since the inception of anion-π interactions, their nature and functional relevance have intrigued researchers. We address the twin challenge of elucidation of the role of extended conjugation and design of all-carbon neutral anion receptors by computations on the anion-π complexes of the halide ions with graphynes. Leveraging on the extended π-conjugation effects, we unfurl the functional relevance of graphynes as anion receptors using descriptors such as electrostatic potential, quadrupole moments, molecular polarizabilities and binding energies. Further, employing natural energy decomposition analysis, we assert that anion-π interactions are not merely dominated by electrostatic interactions. The polarization components do indeed play a crucial role in governing the binding of the anions to the graphynes.

Chloride Binding Modulated by Anion Receptors Bearing Tetrazine and Urea.

Modulation and fine-tuning of the strength of weak interactions to bind anions are described in a series of synthetic receptors. The general design of the receptors includes both a urea motif and a tetrazine motif. The synthetic sequence towards three receptors is detailed. Impacts of H-bond strength and linker length between urea and tetrazine on chloride complexation are studied. Binding properties of the chloride anion are examined in both the ground and excited states using a panel of analytical methods (NMR spectroscopy, mass spectrometry, UV/Visible spectroscopies, and fluorescence). A ranking of the receptors by complexation strength has been determined, allowing a better understanding of the structure-properties relationship on these compounds.

One Hundred Carboxylate Receptors.

This work presents a compilation of binding constant (logKass) values in DMSO-d6/H2O (0.5% m/m) for a variety of receptors with 12 carboxylate anions (formate, acetate, lactate, pivalate, sorbate, hexanoate, benzoate, glyphosate, glucuronate, ibuprofen, naproxen, and ketoprofen). A total of 489 logKass values are listed for 100 anion receptor molecules. Most logKass values originate from previously published articles, along with some values for previously unpublished receptor molecules, spanning a workflow of 8 years. The purpose of this study is to serve as a comprehensive information source for selecting suitable receptor candidates to be used in practical carboxylate sensing applications, such as constructing ion-selective electrodes (ISE-s). To support such decision making, all receptors are presented together with lipophilicity (logPo/w) data.

A Charge-Neutral Self-Assembled L2Zn2 Helicate as Bench-Stable Receptor for Anion Recognition at Nanomolar Concentration.

The field of anion recognition chemistry is dominated by two fundamental approaches to design receptors. One relies on the formation of covalent bonds resulting in organic and often neutral host species, while the other one utilizes metal-driven self-assembly for the formation of charged receptors with well-defined nanocavities. Yet, the combination of their individual advantages in the form of charge-neutral metal-assembled bench-stable anion receptors is severely lacking. Herein, we present a fluorescent and uncharged double-stranded hydroxyquinoline-based zinc(II) helicate with the ability to bind environmentally relevant dicarboxylate anions with high fidelity in dimethyl sulfoxide (DMSO) at nanomolar concentrations. These dianions are pinned between zinc(II) centers with binding constants up to 145 000 000 M-1. The presented investigation exemplifies a pathway to bridge the two design approaches and combine their strength in one structural motif as an efficient anion receptor.

Calix[4]pyrrole-Based Molecular Capsule: Dihydrogen Phosphate-Promoted 1:2 Fluoride Anion Complexation.

A molecular capsule (1) consisting of two calix[4]pyrroles connected via ethylene diamide linkers has been prepared as an anion receptor. 1H NMR spectroscopic studies carried out in CD2Cl2 revealed that receptor 1 recognizes a variety of anions with different binding modes and stoichiometries. For instance, receptor 1 binds fluoride and acetate with 1:2 receptor/anion stoichiometry and other test anions with 1:1 stoichiometry in solution when their respective tetrabutylammonium (TBA+) salts were used. In contrast, with tetraethylammnium (TEA+) salts, receptor 1 forms 1:2 complexes with chloride and bromide in addition to fluoride, overcoming expected Columbic repulsions between the anions co-bound in close proximity. Receptor 1 is also able to bind oxoanions, such as oxalate (C2O42-), dihydrogen phosphate (H2PO4-), sulfate (SO42-), and hydrogen pyrophosphate (HP2O73-), in the form of 1:1 complexes as the result of presumed cooperation between the two calix[4]pyrrole subunits. The selectivity of receptor 1 for fluoride versus dihydrogen phosphate varies depending on their relative concentrations. For instance, in the presence of less than 1.0 equiv of an equimolar mixture of fluoride and dihydrogen phosphate, receptor 1 shows high selectivity for dihydrogen phosphate. In contrast, in the presence of ≥2.0 anion equiv, receptor 1 binds fluoride preferentially, forming a 1:2 complex. Moreover, when treated with F-, the preformed 1:1 H2PO4- complex of receptor 1 is converted to the corresponding 1:2 receptor/fluoride complex with the release of the prebound dihydrogen phosphate anion. As inferred from gas-phase computations, this seemingly counterintuitive behavior is rationalized in terms of the precomplexed dihydrogen phosphate serving to reduce the reorganization energy required to bind two fluoride anions. The presence of a water molecule in addition to the bound fluoride anions may also favor the formation of the 1:2 F- complex. The present study provides a new approach for fine-tuning the binding selectivity of polytopic anion receptors.

Cover Feature: Mannich Reaction: An Alternative Synthetic Approach for Various Pyrrole‐Based Anion Receptors and Chelating Ligands (Eur. J. Org. Chem. 34/2022)

The Cover Feature illustrates the Mannich reaction as an alternative approach for the synthetic development of structurally diverse pyrrole-based acyclic, tripodal, macrocyclic, and macrobicyclic molecules, which are useful as anion receptors, chelating ligands, and as precursors for further reactions. Background image is the main arena of the C. V. Raman Global University where the corresponding author is currently working at. More information can be found in the Review by T. Guchhait, Satabdi Roy et al.

A molecular tuner: Substituent controlled π/π···hole induced selective colorimetric intramolecular push-pull fluoride sensor

Controlling the anion selectivity of synthetic anion receptors towards a particular anion is challenging task for researcher. In the case of bipodal receptors this become trickier since anion can approach the recognition elements of receptors from any direction. In order to overcome this problem, we adopted the new strategy in which the receptor molecules are functionalized with electron donating and/or withdrawing group. In the way of hunting such a receptors, herein Thio-semicarbazide based chemosensors 1-(2,4-dinitrophenyl)-4-(4-nitrophenyl) thiosemicarbazide L1, and 1-(2,4-dimethylphenyl)-4-(4-nitrophenyl) thiosemicarbazide L2 with electron withdrawing (EW) and donating (ED) groups have been synthesized for selective colorimetric anion sensing. Substituent effects on the strength of those receptors L1 and L2 have been studied by naked-eye colorimetric experiments, Ultraviolet-Visible (UV-Vis) spectrometric titration studies, Fourier-Transform Infrared experiments (FT-IR), 1H-NMR, 19F-NMR spectroscopic studies and Molecular Electrostatic Potential (MEP) surface analysis. When we have nitro substitution on both end of the thio-semicarbazide receptor L1, there were no selectivity was found with anions and receptor L1 shows visible color change with the all the tested anions. On the other hand, instead of nitro, when we have methyl substitution on one end and nitro substitution at an another end of the thio-semicarbazide receptor L2, then the receptor L2 show excellent selectivity towards fluoride ion with high association constant. Additionally, for azide considerable bathochromic shift of 70 nm also observed with reference to absorption values of cyanide and fluoride anion which will clearly distinguish the presence of azide ion from cyanide and fluoride. The observed bathochromic shift is mainly attributed due to the intramolecular charge transfer (ICT). In this work, we have successfully tuned the selectivity of synthesized receptors via generating a push-pull effect originated by electron withdrawing and donation substitutions on both end of the receptor L2. The enhanced selectivity of L2 is achieved by altering the acidity of -NHs of thio-semicarbazide derivative L2 by substituting EW and ED groups. In this present work, we have tuned the selectivity of receptor is via intramolecular push-pull effect by electron withdrawing and donating substituent.

Mannich Reaction: An Alternative Synthetic Approach for Various Pyrrole‐Based Anion Receptors and Chelating Ligands

AbstractThis review article highlights the synthetic design of various pyrrole‐based acyclic, tripodal, macrocyclic, and macrobicyclic Mannich bases and their applications, mainly as anion receptors. By varying the amine‐types and molar proportions of reagents, a range of value‐added Mannich bases are obtained. Herein, the synthesis and properties of several azacalixpyrroles, azacalixdipyrrolylmethanes, and azacryptands are discussed. Emphasis is also given to the applications of pyrrole‐based Mannich bases in the construction of some chelating ligands as one of the steps in multistep organic syntheses. In addition, the use of Mannich products as ligands for synthesizing metal complexes is also described. More importantly, the establishment of Mannich reactions as an alternative approach for traditionally used Schiff's base or aldehyde/ketone‐condensation reactions is delineated.

Fluoride-selective chemosensor based on an anion imprinted fluorescent polymer

The sensing of fluoride ion through convenient and inexpensive methods has become significant analytical goals. The state-of-the-art involves the supporting of urea/thiourea optical discrete anion sensors into a polymeric scaffold. Nevertheless, high levels of selectivity are difficult to achieve, since the colorimetric/fluorometric response is also quenched by other anions such as dihydrogenphosphate. In this work we present, for the first time, the design of a polymeric optical fluoride chemosensor by using the anion-imprinting technique. First, four polymerizable anion receptors containing a urea-type binding site and different fluorophores as signaling units were prepared. One of them (1-(4-vinylphenyl)-3-(1-naphtyl)-urea) shows the most intense fluorescence emission in solution, exhibiting high optical sensitivity only for F– and H2PO4–. The electronic and structural features behind the optical response and anion affinity were elucidated through experimental and computational tools. To enhance the optical sensitivity and selectivity, a fluoride-imprinted polymeric optical sensor was prepared starting from this soluble sensor. The fluorescent emission is 13 times higher for the polymer and it is switched off only in the presence of fluoride, while for the rest of the anions, including H2PO4–, there was almost no optical response. To the best of our knowledge, this is the first fluoride-imprinted polymeric optical sensor reported so far.

An Inorganic-Rich SEI Layer Enabled By Hydrogen-Bonding-Catalyzed LiNO3 Reduction for Stable Lithium Metal Batteries

Lithium metal anodes(LMAs) have been considered as the most promising anode candidates due to its high gravimetric capacity (3860 mAh g-1) and low electrode potential (-3.04 V vs S.H.E.). However, uncontrollable Li dendrite growth and low coulombic efficiency hinder practical application of LMAs, causing safety hazard and short cycle life [1]. Among several strategies to prevent Li dendrite growth, introducing the electrolyte additives is one of the most attractive approaches considering its simplicity and cost-effectiveness. Construction of a stable solid electrolyte interphase layer (SEI) is a prerequisite for the stable LMA, hence traditional remedy was introducing the SEI-forming additives in the electrolyte to form stable and robust SEI layer. However, SEI-forming additives cannot guarantee prolonged cycle life after a depletion of the additives, so another strategy is urgently needed.Recently, deposition-regulating additives show great opportunities in the LMA research field as shown in several researches [2,3]. These additives adsorb on the electrode surface and regulate Li deposition behavior to gain dendrite-free Li deposits. However, electrochemical working mechanism of these additives needs further investigation. These researches usually focus on their effect on the Li deposition kinetics, not on the SEI formation despite of the strong adsorption of additives on the electrode interface. Meanwhile, those deposition-regulating additives are not solely used, but often use LiNO3 as SEI forming co-additive. However, the interaction between those additives and LiNO3 is still veiled, despite the possibility of changed reduction behavior by additive-adsorbed surface. In this aspect, investigating interplay between deposition-regulating additive and LiNO3 is important for the deeper understanding of their working mechanism in the LMAs.In this contribution, we first report the synergetic effect of thiourea (TU) with LiNO3 on the SEI formation, and we constructed inorganic-rich ASEI layer by using thiourea as a proof-of-study. Thiourea is known as one of the deposition-regulation additives, which adsorbs on the Li metal surface and help to gain smooth Li deposits [3]. TU shows adsorptive behavior on several metal electrodes by S atom, while two N-H hydrogen bonds are toward the electrolyte side which may interact with anions [4]. Additionally, thiourea has been utilized as an anion receptor and shows strong interaction with NO3 - anion, which is good hydrogen bonding acceptor [5]. In this aspect, we could guess that abundance of NO3 - anion can be achieved in the presence of thiourea on the electrode surface by forming hydrogen bonding, resulting in inorganic-rich SEI layer.To investigate the adsorption behavior of TU on the Cu electrode, differential capacitance was measured and shown in Figure 1(a). In particular, with increment of TU concentration, PZC decreases, indicates more covered surface by TU. To investigate the interaction of TU with other electrolyte components, 1H NMR spectra of different components were conducted and shown in Figure 1(b). Addition of the other components resulted in upshift displacement of N-H bond of TU, implying weakened intramolecular hydrogen bonding of TU. In contrast, addition of LiNO3 resulted in downshift displacement meaning that NO3 - might form strong hydrogen bonding with TU. Also, linear scanning voltammetry (LSV) curves with different concentration of TU were conducted and shown in Figure 1(c) to investigate the effect of TU on electrolyte reduction. The characteristic peaks of LiNO3 and LiTFSI appear at 1.6 V and 1.3 V in the cell with 5wt% LiNO3. When TU is added in the electrolyte, those peaks shift negatively while showing higher current, might be due to catalytic contribution of TU on LiNO3 reduction.To verify the effect of catalyzed LiNO3 reduction on SEI component, we constructed ASEI film on the Cu electrode and conducted XPS measurement. As shown in Figure 2(a-b), abundant LiNxOy and Li3N components are found on ASEI with TU compared with ASEI without TU. Consequently, compared to Li|Cu@NSEI and Li |Cu@ASEI w/o TU, Li|Cu@ASEI with TU shows better cyclability and higher average CE of 96.44% during 80 cycles, as shown in Figure 3. We presumably conclude that better electrochemical performance of Li|Cu@ASEI with TU is would be due to catalyzed reduction of LiNO3 with the aid of thiourea N-H bond. Detailed working mechanism of TU and property of thiourea-modified ASEI will be further presented.

Tritopic Bis-Urea Receptors for Anion and Ion-Pair Recognition.

This work reports on the synthesis and characterization of three tritopic receptors and their binding properties toward various anions, as their tetrabutylammonium salts, and three alkali metal–acetate salts by UV–vis, fluorescence, 1H, 7Li, 23Na, and 39K NMR in MeCN/dimethyl sulfoxide (DMSO) 9:1 (v/v). Molecular recognition studies showed that the receptors have good affinity for oxyanions. Furthermore, these compounds are capable of ion-pair recognition of the alkali metal–acetate salts studied through a cooperative mechanism. Additionally, molecular modeling at the density functional theory (DFT) level of some lithium and sodium acetate complexes illustrates the ion-pair binding capacity of receptors. The anion is recognized through strong hydrogen bonds of the NH– groups from the two urea sites, while the cation interacts with the oxygen atoms of the polyether spacer. This work demonstrates that these compounds are good receptors for anions and ion pairs.

Anion binding by receptors containing NH donating groups – What do anions prefer?

Understanding the interplay between host structure and its ion-binding ability is one of the fundamental tasks in host-guest chemistry, as this allows prediction of their behaviour as supramolecular receptors. We tackled this issue in the present work by studying a series of aromatic amide derivatives and a hybrid urea-amide derivative as anion receptors in DMSO by 1H NMR and UV–Vis titrations. We found that the amide derivatives formed complexes of 1:1 stoichiometry with the tested anions (H2PO4−, AcO−, Cl−) and that both amide NH-groups were involved in the anion coordination. Spectral changes accompanying the complexation reaction also revealed that certain aromatic CH groups acted as hydrogen-bond donors aiding the complex stabilisation. In the cases of acetate or chloride, the hybrid urea-amide receptor 6H bound one anion engaging only the urea group as the binding site. In contrast, when dihydrogen phosphate was added to 6H the 1:1 and 2:1 complexes (anion:receptor) were detected. Again, the 1:1 complex was stabilized only by H-bonds with urea as the binding site. On the other hand, in the case of complex comprising two anions, the amide group participated in stabilisation and strong interanionic hydrogen bonds were formed. The gathered results addressed the title question, revealing that simple anions prefer to bind to urea when offered an amide or urea groups as binding sites without significant steric constraints. However, the presence of an amide group can facilitate the formation of higher complexes in specific cases.

Ion-Pairing Assemblies of Anion-Responsive π-Electronic Systems Bearing Triazole Moieties Introduced by Click Chemistry.

In this study, the diverse derivatives of dipyrrolyldiketone boron complexes as anion-responsive π-electronic systems were synthesized via the Huisgen cycloaddition of an ethynyl-substituted anion receptor and azide derivatives. The obtained triazole-substituted anion receptors showed effective anion-binding behaviors and ion-pairing assemblies comprising receptor-anion complexes and countercations. Solid-state ion-pairing structures were modulated according to the introduced azide moieties along with coexisting bulky and π-electronic cations.

Moisture-Sensitive Ratiometric Color-Changing Response: a Useful Tool for Precision Farming

Anthra[1,2-d]imidazole-6,11-dione-based charge transfer probes have been developed for the detection of water impurities in a wide range of laboratory-used organic solvents. The deprotonated (anionic) forms of the probe molecules, obtained upon addition of basic anions such as fluoride, demonstrate a ratiometric color-changing response (blue to yellow in presence of F– and red to yellow with CN– ion) even in the presence of a trace amount of moisture (detection limit: 0.008 wt %). Considering their high sensitivity and “naked-eye” response, the anionic receptors are utilized for the quantification of moisture level or water impurity in a wide range of real-life samples, such as building raw materials, packaged food items, soil, plant leaves, and so on. Determination of the moisture level of plant leaves or soil samples is particularly important for precision farming as it helps the farmers to schedule the irrigation events. Finally, low-cost, reusable, and optical kit-based dye-coated paper strips were developed for rapid, on-location detection as well as quantification purposes. Since such a sustainable approach does not involve any sophisticated instruments or complex sample preparation steps, the general public with little knowledge of science or technology will be able to use it without much difficulty.

Synthesis, characterization and hirshfeld surface analyses of Ni(mnt)-alkyl bis(imidazolium) ion pair compounds: Supramolecular interactions mediated self-assembly

A series of five new ion pair compounds with formulae [C9H14N4][Ni(mnt)2](CH3CN) (1a), [C10H16N4][Ni(mnt)2] (1b), [C11H18N4][Ni(mnt)2] (1c), [C12H20N4][Ni(mnt)2] (1d), [C13H22N4][Ni(mnt)2] (1e) have been synthesized from Ni(II) salts, Na2mnt (disodium maleonitriledithiolate) and alkyl-bis(imidazolium) cations [C8H12(CH2)nN4Br2] (n = 1 − 5). All the compounds were characterized by IR, elemental analyses, UV, and electrochemical studies. The solid-state structures of these compounds were characterized by single crystal X-diffraction, facilitated by Hirshfeld surface analyses, to quantify the type and magnitude of various non-covalent interactions controlling the self-assembly. Various supramolecular interactions CHcation···Nanion, CHcation···Sanion and CH···π play a crucial role in modulating the conformations of cationic and anionic receptors as well as mediating the self-assembly. Hirshfeld surface analyses reveals that supramolecular packing is dominated by the directional interactions in lower chain cationic receptors whereas, non-directional interactions operate in longer chain cationic receptors. Absorption spectra reveals compound 1d exhibits absorption band (diffuse reflectance) at 910 nm whereas others at 860 nm. All the compounds show oxidative response in the region 0.48−0.56 V in the electrochemical studies. Additionally, the phase purity of the compounds were confirmed by the powder X-ray diffraction studies.

A highly selective superphane for ReO4− recognition and extraction

Highly selective anion recognition and extraction is challenging and yet critical for removal of pollutants from the environment and the effective recovery of valuable chemicals from low-content (at sub-ppm or ppb level) sources. In this paper, we detail the gram-scale synthesis of a superphane 2 , an anion receptor that selectively binds ReO 4 − . Superphane 2 can extract perrhenate from solid mixtures containing traces of ReO 4 − anion (as low as 200 ppb) and aqueous media with near 100% selectivity over large excesses of competing anions. Meanwhile, up to 99.99% of ReO 4 − can be separated from complex simulated aqueous waste streams containing ppm-level perrhenate via either liquid-liquid extraction or simple column adsorption. Importantly, after extraction or adsorption, superphane 2 can be recycled and reused by simple treatment with aqueous NaHCO 3 . • A superphane for highly selective recognition of ReO 4 − is synthesized in gram scale • Over 99.99% of ReO 4 − can be separated from complex simulated waste streams • Rapid removal of ppb-level ReO 4 − is achieved via extraction or column adsorption • The superphane for ReO 4 − extraction/adsorption can be recycled and reused Extraction of low concentrations of rhenium anions from waste streams is important industrially. Zhou et al. present the facile and gram-scale synthesis of a superphane via dynamic imine chemistry coupled with NaBH 4 reduction, which can separate perrhenate from low-content mixtures and simulated Hanford waste streams with exceptionally high efficiency and selectivity, along with good recyclability and reusability.

A Photoresponsive Receptor with a 105 Magnitude of Reversible Anion-Binding Switching.

Invited for the cover of this issue are Jeffrey Einkauf, Vyacheslav Bryantsev, Bruce Moyer, and Radu Custelcean from Oak Ridge National Laboratory. The image depicts an anion receptor functionalized with a new photoswitchable chromophore, the diiminoguanidinium group, with exceptionally strong sulfate-binding affinity that can be turned off by photoirradiation with UV light. Read the full text of the article at 10.1002/chem.202200719.

Perivascular adipose tissue modulates the effects of flavonoids on rat aorta rings: Role of superoxide anion and β3 receptors

Several studies demonstrate the beneficial effects of dietary flavonoids on the cardiovascular system. Since perivascular adipose tissue (PVAT) plays an active role in the regulation of vascular tone in both health and diseases, the present study aimed to assess the functional interaction between PVAT and flavonoids in vitro on rat aorta rings. Several flavonoids proved to display both antispasmodic and spasmolytic activities towards noradrenaline-induced contraction of rings deprived of PVAT (-PVAT). However, on PVAT-intact (+PVAT) rings, both actions of some flavonoids were lost and/or much decreased. In rings-PVAT, the superoxide donor pyrogallol mimicked the effect of PVAT, while in rings+PVAT the antioxidant mito-tempol restored both activities of the two most representative flavonoids, namely apigenin and chrysin. The Rho-kinase inhibitor fasudil, or apigenin and chrysin concentration-dependently relaxed the vessel active tone induced by the Rho-kinase activator NaF; the presence of PVAT counteracted apigenin spasmolytic activity, though only in the absence of mito-tempol. Similar results were obtained in rings pre-contracted by phenylephrine. Finally, when β3 receptors were blocked by SR59230A, vasorelaxation caused by both flavonoids was unaffected by PVAT. These data are consistent with the hypothesis that both noradrenaline and apigenin activated adipocyte β3 receptors with the ensuing release of mitochondrial superoxide anion, which once diffused toward myocytes, counteracted flavonoid vasorelaxant activity. This phenomenon might limit the beneficial health effects of dietary flavonoids in patients affected by either obesity and/or other pathological conditions characterized by sympathetic nerve overactivity.

Front Cover: A Photoresponsive Receptor with a 105 Magnitude of Reversible Anion‐Binding Switching (Chem. Eur. J. 26/2022)

A new photoswitchable chromophore, the diiminoguanidinium group can be used as the base for an anion receptor based. Like the yin-yang (dark–light) relationship between the Moon and the Sun, the E,E and Z,Z photoisomers of the 2-pyridyl-diiminoguanidinium receptor have opposite binding behaviors towards sulfate, a representative oxyanion. The open E,E form binds sulfate with extraordinary strength in the dark, through chelating guanidinium hydrogen bonds. Upon photoisomerization to the Z,Z isomer, the anion-binding site is shut off, thereby ejecting the bound sulfate anion. More information can be found in the Research Article by B. A. Moyer, R. Custelcean and co-workers (DOI: 10.1002/chem.202200719).