Preorganization Effect Research Articles

Enhanced Near-infrared Phosphorescent Emission Modulated by Clipping of Metallotweezers in Aqueous Media.

Near-infrared phosphorescent materials have received significant attention due to their potential applications in bioimaging and diagnostics. Although, many types of organic phosphors with near-infrared emission have been developed, the low phosphorescence efficiency in aqueous solution hampers their practical applications in biological systems. Hence, there is an urgent need to develop near-infrared phosphorescent materials with high emission efficiency in aqueous media. Metallotweezers, based on d8 transition metal complexes, emerge as the potential candidates for realizing this objective. Specifically, metallotweezers, featuring two positively charged platinum(II) terpyridine and neutral gold(III) diphenylpyridine pincers on diphenylpyridine spacer, have been designed and synthesized, respectively. The pre-organization effect, rendered by the rigid spacer, enables the resulting metallotweezers to complex with each other, resulting in the formation of clipping complex. The synergistic rigidifying and shielding effects of clipping structure results in enhanced phosphorescent emission intensity. Concurrently, due to phase segregation between the clipping units and the polyethylene glycol tail, the clipping complex undergoes self-assembly in aqueous solution, resulting in phosphorescent emission in the near-infrared region. Overall, non-covalent clipping of metallotweezers illustrated in this study presents a new and effective approach toward near-infrared phosphorescent materials.

Achieving Circularly Polarized Phosphorescence through Noncovalent Clipping of Metallotweezers.

Circularly polarized phosphorescent materials, based on host-guest complexation, have received significant attention due to their outstanding emission performance in solutions. Recent studies have primarily focused on macrocyclic host-guest complexes. To broaden the scope of this research, there is a keen pursuit of developing novel chiral phosphorescent host-guest systems. Metallotweezers with square-planar d8 transition metal complexes emerge as promising candidates for achieving this objective. Specifically, metallotweezers, comprising platinum(II) terpyridine and gold(III) diphenylpyridine pincers on a diphenylpyridine scaffold, have been designed and synthesized. Due to the preorganization effect rendered by the diphenylpyridine scaffold, the resulting metallotweezers are capable of complexing with each other and forming quadruple stacking structures. The phosphorescent emission is enhanced owing to the synergistic rigidifying and shielding effects. Meanwhile, the steric effect of chiral (1R) pinene units on the platinum(II) terpyridine pincers results in a stereospecific twist for the quadruple stacking structures. Thus, the chirality transfers from the molecular to the supramolecular level. By a combination of phosphorescent enhancement and supramolecular chirality for the clipping complex, circularly polarized phosphorescent emission is achieved. Overall, noncovalent clipping of metallotweezers exemplified in the current study presents a novel and effective approach toward solution-processable circularly polarized phosphorescent materials.

One-Step Catalyst-Transfer Macrocyclization: Expanding the Chemical Space of Azaparacyclophanes.

In this paper, we report on a one-step catalyst-transfer macrocyclization (CTM) reaction, based on the Pd-catalyzed Buchwald-Hartwig cross-coupling reaction, selectively affording only cyclic structures. This route offers a versatile and efficient approach to synthesize aza[1n]paracyclophanes (APCs) featuring diverse functionalities and lumens. The method operates at mild reaction temperatures (40 °C) and short reaction times (∼2 h), delivering excellent isolated yields (>75% macrocycles) and up to 30% of a 6-membered cyclophane, all under nonhigh-dilution concentrations (35-350 mM). Structural insights into APCs reveal variations in product distribution based on different endocyclic substituents, with steric properties of exocyclic substituents having minimal influence on the macrocyclization. Aryl-type endocyclic substituents predominantly yield 6-membered macrocycles, while polycyclic aromatic units such as fluorene and carbazole favor 4-membered species. Experimental and computational studies support a proposed mechanism of ring-walking catalyst transfer that promotes the macrocycle formation. It has been found that the macrocyclization is driven by the formation of cyclic conformers during the oligomerization step favoring an intramolecular C-N bond formation that, depending on the cycle size, hinges on either preorganization effect or kinetic increase of the reductive elimination step or a combination of the two. The CTM process exhibits a "living" behavior, facilitating sequential synthesis of other macrocycles by introducing relevant monomers, thus providing a practical synthetic platform for chemical libraries. Notably, CTM operates both under diluted and concentrated regimes, offering scalability potential, unlike typical macrocyclization reactions usually operating in the 0.1-1 mM range.

Enhanced Chemiluminescence under the Nanoconfinement of Covalent-Organic Frameworks and Its Application in Sensitive Detection of Cancer Biomarkers.

Chemiluminescence (CL) with intensive emission has been pursued for decades. It is still challenging to find a new mechanism to enhance CL. In this work, confinement-enhanced CL was developed for the first time by the coembedding of N-(aminobutyl)-N-(ethylisoluminol) (ABEI) and Co2+ into gold nanoparticle-modified covalent-organic frameworks (COFs). For the consideration of improving the hydrophilicity of COFs and facilitating subsequent biological modification, gold nanoparticles were first reduced on the COF surface (Au-COF) in situ without other reducing reagents. By virtue of the abundant imine bond and π backbones, ABEI and Co2+ were embedded in Au-COF synergistically through π-π stacking and coordination. The confinement of ABEI and Co2+ into Au-COF brought an over 20-fold enhancement of CL intensity compared to that of adding them to a liquid phase, which benefitted from the three aspects of the confinement effect, including the molecular enrichment effect, the physical constraint effect, and the molecular preorganization effect. As proof of concept, a lipid-protein dual-recognition sandwich strategy based on this CL-functionalized COF was developed for the detection of breast cancer cell line-derived extracellular vesicles (EVs) with four orders of magnitude improvement in the detection limit compared to ELISA. The successful distinction of human epidermal growth factor receptor 2 (HER2)-positive patients from HER2-negative patients indicated the great application potential of the proposed bioassay in HER2-positive breast cancer diagnosis. This work proposed a novel enhancement mechanism for CL based on crystalline porous materials, which provides a new perspective for the development of CL-functionalized materials for biosensors and bioassays.

Analyzing the Reaction of Orotidine 5'-Phosphate Decarboxylase as a Way to Examine Some Key Catalytic Proposals.

This study analyzes the origin of enzyme catalysis by focusing on the reaction of orotidine 5'-phosphate decarboxylase (ODCase). This reaction involves an enormous catalytic effect of 23 kcal/mol that has been attributed to reactant state destabilization associated with the use of binding energy through the so-called Circe effect. However, our early studies and subsequent key experiments have shown that the presumed effect of the binding energy (namely, the strain exerted by a bond to a phosphate group) does not contribute to the catalysis. In this study, we perform quantitative empirical valence bond calculations that reproduce the catalytic effect of ODCase and the effect of removing the phosphate side chain. The calculations demonstrate that the effect of the phosphate is due to a change in reorganization energy and should not be described as an induced fit effect. Similarly, we show that the overall catalytic effect is due to electrostatic transition state stabilization, which again reflects the smaller reorganization energy in the enzyme than in water. We also elaborate on the problems with the induced fit proposal, including the fact that it does not serve to tell us what the actual origin of the action of the catalytic effect is. In addition to the above points, we use this paper to discuss misconceptions about the meaning of the preorganization effect, as well as other misunderstandings of what is being done in consistent calculations of enzyme catalysis.

Bioinspired Electron Polarization of Nanozymes with a Human Self-Generated Electric Field for Cancer Catalytic Therapy.

Reactive oxygen species (ROS) production efficiencies of the nanocatalysts are highly desired for cancer therapy, but currently the ROS generation efficiency is still far from defecting the tumors. Therefore, improving their ROS generation ability is highly desirable for cancer therapy. Herein, inspired by the electrostatic preorganization effect during the catalysis of natural protein enzymes, a human self-driven catalysis-promoting system, TENG-CatSystem is developed, to improve catalytic cancer therapy. The TENG-CatSystem is mainly composed of three elements: a human self-driven triboelectric nanogenerator (TENG) as the electric field stimulator to provide electric pulses with high biosafety, a nanozyme comprising a 1D ferriporphyrin covalent organic framework coated on a carbon nanotube (COF-CNT) to generate ROS, and a COF-CNT-embedded conductive hydrogel that can be injected into the tumor tissues to increase local accumulation of COF-CNT and decrease the electrical impedances of tissues. Under the human self-generated electric field provided by the wearable TENG, the peroxidase-like activity of the COF-CNT is fourfold higher than that without an electric field. Highly malignant 4T1 breast carcinoma in mice is significantly suppressed using the TENG-CatSystem. The human self-driven TENG-CatSystem not only demonstrates high catalytic ROS generation efficiency for improved cancer therapy, but also offers a new therapeutic mode for self-driven at-home therapy.

Supramolecular preorganization effect to access single cobalt sites for enhanced photocatalytic hydrogen evolution and nitrogen fixation

Ever-increased investigation has been focused on designing photocatalysts comprising intimately interfaced photo-absorbers and co-catalysts for promoting the separation of electron-hole pairs and surface redox reaction. Herein, we present a photocatalytic system in which the single-site-cobalt-atom is firmly trapped and stabilized into the frameworks of porous crimped graphitic carbon nitride (g-C3N4), proposing as advanced photocatalysts for solar-photon-driven hydrogen production and nitrogen fixation. A single molecular source of dicyandiamide was used to partly transformed and then in-situ preorganized into supermolecular precursor, which could coordinate with cobalt ions and manipulate the interactions under elevated temperature prior to the condensation to form atomically Co dispersed g-C3N4 materials. Theoretical evaluation and experimental validation identified that the chemical integration of single-site-cobalt-atom on g-C3N4 is critical in optimizing the electron and band structures and accelerating the interfacial charge transfer process. As a result, the as-obtained Co@g-C3N4 possesses an exceptional photocatalytic hydrogen production rate (2481 μmolh−1g−1, λ > 420 nm) and conspicuous nitrogen photofixation performances under visible-light irradiation. Such concerted catalysis attributes to the negative shift of the Fermi level in Co@g-C3N4 system deriving from the induced charge-transfer effect, which effectively gains the reducibility of electrons and creates more active sites for photocatalytic reactions.

Experimental and theoretical studies on structure, bonding and luminescence properties of Eu(III) and Tb(III) complexes of a new macrocyclic based 8HQ ligand

8-Hydroxyquinolate complexes of lanthanide have a variety of applications in electroluminescent devices due to their unique luminescence properties. But, the simple 8HQ ligand has a tendency to form polynuclear complexes. However, linking several 8HQ units to a single moiety facilitates the formation of mononuclear complexes due to flexibility, preorganization, π-stacking and entropy effect. Mononuclear complexes of europium and terbium ions with a new chelator, [1,4,7-tris-{(5-methylene-8-hydroxyquinoline)-1,4,7-triazacyclononane}], embedded with these prerequisites are synthesized and characterized. Each Ln(III) is nine-coordinate and bonded to three sets of O,N-donors of 8HQ units and three water resulting in a pseudo-C3 symmetric tricapped trigonal prismatic geometry. In silico studies suggest that the metal ion can easily be encapsulated in the central cavity of the ligand without changing its basic structure. Interesting, diverse behavior was observed for photoluminescence spectral studies in solid and solution state. At room temperature, an antenna effect was observed for the complexes only in the powder form. The experimental photoluminescence studies have been explained with the help of TDDFT. The nature of bonding between the lanthanide and the ligand, interpreted by NBO and ETS-NOCV, suggest that the Ln-L bonds are ∼25% covalent. The Slater Condon parameters, spin-orbital coupling constants, and the nephelauxetic parameters were calculated from LF-DFT.

Theoretical study on steric effects, electronic properties, preorganization and solvent effect in host–guest chemistry of hexaprotonated form of an azacyclophane and halide anions

A theoretical study on the selectivity of hexaprotonated form of preorganized azacyclophane C3-trenphen (H6 L 6+) for halide anions in the gas phase and solution is reported. The calculated formation and interaction energies show the following trend: [F⊂H6 L]5+ > [Cl⊂H6 L]5+ > [Br⊂H6 L]5+ > [I⊂H6 L]5+. Our calculations in both the gas phase and solution, in agreement with the experimental observations, show that the H6 L 6+ host has the largest selectivity for fluoride anion. Indeed, the stronger host–guest interaction in [F⊂H6 L]5+ complex effectively compensates the unfavourable strain energy of the host and desolvation energy of fluoride anion. Furthermore, herein, the solvent effect does not change the observed trend for gas-phase formation energies. In continuation, in order to find the origin of longer X−···aromatic ring (X−···cntr) distance than X−···bridgehead nitrogen (X−···Napical) in the present complexes, the X−···C6H6 and X−···NH3 systems were simulated, respectively. The calculated interaction energies for two latter systems in different X−···C6H6 and X−···NH3 distances clearly showed that the repulsion force between X− and nitrogen atom is larger than that between X− and aromatic ring. Thus, only when there are the strong N–H···X− interactions in top of the cage, the Napical···X− distance is considerably smaller than cntr···X− one.

Synthesis, Ion Recognition Ability, and Metal-Assisted Aggregation Behavior of Dinuclear Metallohosts Having a Bis(Saloph) Macrocyclic Ligand.

Macrocyclic molecule 1 that has two saloph coordination sites was designed and synthesized. The macrocycle 1 was easily converted into the corresponding metallohosts 2 and 3 by the reaction with nickel(II) and palladium(II), respectively. As expected from the molecular structure of these metallohosts having an 18-crown-6-like cavity, the nickel(II) metallohost 2 showed excellent binding affinity toward Na(+), Ca(2+), and Sr(2+) to give 1:1 host-guest complexes. Preorganization effect due to the extremely rigid metal-containing macrocycle was suggested to be a major factor for the strong binding. Larger cations such as K(+), Rb(+), Cs(+), and Ba(2+) gave higher aggregated host-guest complexes such as 22M, 23M2, and 24M3. Density functional theory calculations revealed that smaller metal ions do not occupy the center of each macrocycle in the sandwich structures 22M, while larger Cs(+) simultaneously interacts with all the 12 oxygen donor atoms. On the basis of the interaction energy calculations, the preference for 2·Na over 22Na can be explained by destabilization of 22Na due to the elongated Na-O bonds and repulsive three-body interactions. When the ionic radius of the guest ion increases (K(+), Rb(+), Cs(+)), this destabilization becomes less significant and the formation of sandwich complexes 22M is favored. Such aggregation would significantly affect the physical and chemical properties of the metal complexes due to the interplane interactions between the metal centers.

Chiral imidazolium receptors for citrate and malate: the importance of the preorganization.

A family of simple receptors formed by two or three cationic imidazolium arms attached to a central aromatic linkage and displaying different conformational flexibility has been synthesized from the enantiopure (1S,2S)-2-(1-H-imidazol-1-yl)-cyclohexanol. The crystal structures of the corresponding bromides of two of the hosts showed remarkable differences. The tripodal receptor with a trimethylated central benzene ring (1a) showed a cone-type conformation defining an inner anion-binding site, while the bipodal molecule with the central meta-phenylene spacer (m-2a) displayed an extended conformation. The binding properties of the chiral imidazolium hosts toward citrate, isocitrate and the two enantiomers of malate have been studied by (1)H NMR titration experiments in 9:1 CD3CN:CD3OH at 298.15 K. Interestingly, 1a showed a stronger interaction with dianionic malate than with the trianionic citrate or isocitrate, suggesting that the smaller guest is better accommodated in the host cavity. Among this family, 1a proved to be the best receptor due to a combination of a larger number of electrostatic and H-bonding interactions and to a more efficient preorganization in the cone-type conformation. This preorganization effect is also present in solution as confirmed by (1)H NMR spectroscopy.

Rational design of protein stability: effect of (2S,4R)-4-fluoroproline on the stability and folding pathway of ubiquitin.

BackgroundMany strategies have been employed to increase the conformational stability of proteins. The use of 4-substituted proline analogs capable to induce pre-organization in target proteins is an attractive tool to deliver an additional conformational stability without perturbing the overall protein structure. Both, peptides and proteins containing 4-fluorinated proline derivatives can be stabilized by forcing the pyrrolidine ring in its favored puckering conformation. The fluorinated pyrrolidine rings of proline can preferably stabilize either a Cγ-exo or a Cγ-endo ring pucker in dependence of proline chirality (4R/4S) in a complex protein structure. To examine whether this rational strategy can be generally used for protein stabilization, we have chosen human ubiquitin as a model protein which contains three proline residues displaying Cγ-exo puckering.Methodology/Principal FindingsWhile (2S,4R)-4-fluoroproline ((4R)-FPro) containing ubiquitinin can be expressed in related auxotrophic Escherichia coli strain, all attempts to incorporate (2S,4S)-4-fluoroproline ((4S)-FPro) failed. Our results indicate that (4R)-FPro is favoring the Cγ-exo conformation present in the wild type structure and stabilizes the protein structure due to a pre-organization effect. This was confirmed by thermal and guanidinium chloride-induced denaturation profile analyses, where we observed an increase in stability of −4.71 kJ·mol−1 in the case of (4R)-FPro containing ubiquitin ((4R)-FPro-ub) compared to wild type ubiquitin (wt-ub). Expectedly, activity assays revealed that (4R)-FPro-ub retained the full biological activity compared to wt-ub.Conclusions/SignificanceThe results fully confirm the general applicability of incorporating fluoroproline derivatives for improving protein stability. In general, a rational design strategy that enforces the natural occurring proline puckering conformation can be used to stabilize the desired target protein.

On catalytic preorganization in oxyanion holes: highlighting the problems with the gas-phase modeling of oxyanion holes and illustrating the need for complete enzyme models.

Oxyanion holes play a major role in catalyzing enzymatic reactions, yet the corresponding energetics is frequently misunderstood. The main problem may be associated with the nontrivial nature of the electrostatic preorganization effect, without following the relevant formulation. That is, although the energetics of oxyanion holes have been fully quantified in early studies (which include both the enzymatic and reference solution reactions), the findings of these studies are sometimes overlooked, and, in some cases, it is assumed that gas-phase calculations with a fixed model of an oxyanion hole are sufficient for assessing the corresponding effect in the protein. Herein, we present a systematic analysis of this issue, clarifying the problems associated with modeling oxyanions by means of two fixed water molecules (or related constructs). We then re-emphasize the point that the effect of the oxyanion hole is mainly due to the fact that the relevant dipoles are already set in an orientation that stabilizes the TS charges, whereas the corresponding dipoles in solution are randomly oriented, resulting in the need to pay a very large reorganization energy. Simply calculating interaction energies with relatively fixed species cannot capture this crucial point, and considering it may help in advancing rational enzyme design.

Ketosteroid isomerase provides further support for the idea that enzymes work by electrostatic preorganization

One of the best systems for exploring the origin of enzyme catalysis has been the reaction of ketosteroid isomerase (KSI). Studies of the binding of phenolates to KSI have been taken as proof that the electrostatic preorganization effect only makes a minor contribution to the binding of the real, multiring, transition state (TS). However, our simulation study has determined that the difference between the phenolates and the TS arises from the fact that the nonpolar state of the phenolate can rotate freely relative to the oxyanion hole and thus loses the preorganization contribution. A recent study explored the reactivity of both small and multiring systems and concluded that their similar reactivity contradicts our preorganization idea. Herein, we establish that the available experiments in fact provide what is perhaps the best proof and clarification of the preorganization idea and its crucial role in enzyme catalysis. First, we analyze the binding energy and the pK(a) of equilenin and identify direct experimental evidence for our prediction about the differential electrostatic stabilization of the large TS and the small phenolates. Subsequently, we show that the similar reactivity of the small and large systems is also due to an electrostatic preorganization effect but that this effect only appears in the intermediate state because the TS is not free to rotate. This establishes the electrostatic origin of enzyme catalysis. We also clarify the crucial importance of having a well-defined physical concept when examining catalytic effects and the need for quantitative tools for analyzing such effects.

Toward Accurate Screening in Computer-Aided Enzyme Design

The ability to design effective enzymes is one of the most fundamental challenges in biotechnology and in some respects in biochemistry. In fact, such ability would be one of the most convincing manifestations of a full understanding of the origin of enzyme catalysis. In this work, we explore the reliability of different simulation approaches, in terms of their ability to rank different possible active site constructs. This validation is done by comparing the ability of different approaches to evaluate the catalytic contributions of various residues in chorismate mutase. It is demonstrated that the empirical valence bond (EVB) model can serve as a practical yet accurate tool in the final stages of computer-aided enzyme design (CAED). Other approaches for fast screening are also examined and found to be less accurate and mainly useful for qualitative screening of ionized residues. It is pointed out that accurate ranking of different options for enzyme design cannot be accomplished by approaches that cannot capture the electrostatic preorganization effect. This is in particular true with regard to current design approaches that use gas phase or small cluster calculations and then estimate the interaction between the enzyme and the transition state (TS) model rather than the TS binding free energy or the relevant activation free energy. The ability of the EVB model to provide a tool for quantitative ranking in the final stage of CAED may help in progressing toward the design of enzymes whose catalytic power is closer to that of native enzymes than to that of the current generation of designer enzymes.

Selective binding of benzenediol derivatives by simultaneous non-covalent interactions in bis-Pt(II) aza-aromatic host–guest system

We have designed and synthesized a new ligand, 6-(2-pyridinyl)-4-[3'-(3-pyridinyl)[1,1'-biphenyl]-3-yl]-2,2'-bipyridine (2). 2 reacted with Pt(cod)(MeCN)(2)(BF(4))(2) to quantitatively give the molecular dimer, 1.BF(4) (2(2).Pt(II)(2).4BF(4)(-)), by self-assembly. The (1)H NMR and UV-vis titration showed that the complexation affinity of 1.BF(4) toward benzenediol guests decreases in the order para > meta > ortho. The structural analysis revealed that the pi-pi stacking interactions and multiple CH...O hydrogen bonds make the benzenediol binding favorable. DFT calculations showed that complexation with Pt(II) leads to a unique charge distribution in 1 creating more positive sites inside the cavity that provides a strong binding site for benzenediols. The macrocyclic preorganization effect, induced-fit complexation mechanism, Coulombic interactions, such as pi-pi stacking interactions, and CH...O hydrogen bonding contribute to the benzenediol recognition.

The Preorganization Effect of the Calix[4]arene Platform on the Extraction Properties of Acetylhydrazide Groups with Transition Metal Ions

The binding properties of the cone conformer of O,O,O,O-tetrakis[hydrazinocarbonylmethyl]-4-tert-butylcalix[4]arene, the cone and the 1,3-alternate conformers of the corresponding thia analogue have been evaluated by means of liquid–liquid extraction for a large variety of metal ions. The extraction constants and the stoichiometries of the complexes formed have been determined. Comparison of the extraction properties of calix[4]arenes with their acyclic monomeric analogue clearly demonstrated, that the preorganization of acetylhydrazide groups on the calix[4]arene platform is the cause for a significant improvement of its binding properties. The presence of additional “soft” nitrogen binding sites in acetylhydrazide derivatives of calix[4]arenes compared to their amide derivatives leads to a shift from their classical selectivity for alkali and alkaline earth cations to transition metals. The cone conformer of tetrathiacalix[4]arene shows higher selectivity in a series of d-metal ions compared with its “classical” analogue. The 1,3-alternate conformer exhibits an excellent extraction selectivity for Cu2+ and Hg2+.

Synthesis and complexation properties of carbonyl-containing thiacalix[4]arenes

Stereoisomers of thiacalix[4]arenes unsubstituted at the upper rim and containing four carbonyl fragments have been synthesized for the first time. Their structures were studied by 1D and 2D NMR spectroscopy, IR spectroscopy, and mass spectrometry. The complexation properties of the macro-cycles toward alkaline metal cations were estimated by the picrate extraction method. The absence of the preorganization effect in the case of the thiacalixarenes unsubstituted at the upper rim is the main reason for the sharp decrease in their extraction ability.

Molecular Dynamics Studies of Caspase-3

Caspase-3 is a fundamental target for pharmaceutical interventions against a variety of diseases involving disregulated apoptosis. The enzyme is active as a dimer with two symmetry-related active sites, each featuring a Cys-His catalytic dyad and a selectivity loop, which recognizes the characteristic DEVD pattern of the substrate. Here, a molecular dynamics study of the enzyme in complex with two pentapeptide substrates DEVDG is presented, which provides a characterization of the dynamic properties of the active form in aqueous solution. The mobility of the substrate and that of the catalytic residues are rather low indicating a distinct preorganization effect of the Michaelis complex. An essential mode analysis permits us to identify coupled motions between the two monomers. In particular, it is found that the motions of the two active site loops are correlated and tend to steer the substrate toward the reactive center, suggesting that dimerization has a distinct effect on the dynamic properties of the active site regions. The selectivity loop of one monomer turns out to be correlated with the N-terminal region of the p12 subunit of the other monomer, an interaction that is also found to play a fundamental role in the electrostatic stabilization of the quaternary structure. To further characterize the specific influence of dimerization on the enzyme essential motions, a molecular dynamics analysis is also performed on the isolated monomer.

Design and synthesis of preorganized tripodal fluororeceptors based on hydrogen bonding of thiourea groups for optical phosphate ion sensing

Expecting a preorganization effect, tripodal anion host molecules were designed and synthesized. It was demonstrated that two kinds of new thiourea derivatives having a six-fold substituted benzene ring as a preorganized spacer were effective for recognition of the tetrahedral dihydrogen phosphate anion. A tripodal fluororeceptor 1 having a pyrene moiety adjacent to the thiourea binding site showed long-wavelength emission upon addition of guest anions in acetonitrile. On the other hand, a tripodal thiourea receptor 2 connected to anthracene groups via methylene units showed a decrease in fluorescence intensity upon addition of anions. In both cases, the degree of the change in emission intensity was in the order of H2PO4− > CH3COO− > Cl− ≫ ClO4−, which is clearly different from that of reference compounds having only one binding site. Association constants (Ka) of these tripodal fluororeceptors also confirmed the dihydrogen phosphate selectivity over the more basic acetate anion in this homogeneous solution system. The characteristics of the fluororeceptors using the preorganization effect were shown to be promising for the development of chemical ion sensors with a specific anion selectivity.