Experimental and theoretical studies of substituent effects in hydrogen bond based molecular recognition of a zwitterion by substituted arylureas

Wilcox, Craig S.; Kim, Eun-il; Romano, David; Kuo, Lung Huang; Burt, Arthur L.; Curran, Dennis P.

doi:10.1016/0040-4020(94)00921-g

Cited by 123 publications

(74 citation statements)

References 13 publications

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“…However, rate enhancement relative to the solution reaction requires that the strengthening of the H bond to enzymatic catalytic groups be greater than that to water. The steeper dependences of H bond strength on ⌬pK a generally observed in organic solvents and the gas phase than in water suggested that this is possible (10,11,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)36). However, we were aware of no direct comparison of these dependencies in nonaqueous and aqueous media.…”

Section: Discussionmentioning

confidence: 77%

See 1 more Smart Citation

The change in hydrogen bond strength accompanying charge rearrangement: Implications for enzymatic catalysis

Shan

Herschlag²

1996

Proc. Natl. Acad. Sci. U.S.A.

186

197

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The equilibrium for formation of the intramolecular hydrogen bond (K HB ) in a series of substituted salicylate monoanions was investigated as a function of ⌬pK a , the difference between the pK a values of the hydrogen bond donor and acceptor, in both water and dimethyl sulfoxide. The dependence of log K HB upon ⌬pK a is linear in both solvents, but is steeper in dimethyl sulfoxide (slope ‫؍‬ 0.73) than in water (slope ‫؍‬ 0.05). Thus, hydrogen bond strength can undergo substantially larger increases in nonaqueous media than aqueous solutions as the charge density on the donor or acceptor atom increases. These results support a general mechanism for enzymatic catalysis, in which hydrogen bonding to a substrate is strengthened as charge rearranges in going from the ground state to the transition state; the strengthening of the hydrogen bond would be greater in a nonaqueous enzymatic active site than in water, thus providing a rate enhancement for an enzymatic reaction relative to the solution reaction. We suggest that binding energy of an enzyme is used to fix the substrate in the low-dielectric active site, where the strengthening of the hydrogen bond in the course of a reaction is increased.Electronic rearrangement typically occurs in the course of a reaction, resulting in changes in the charge density of functional groups on the reactant. This is shown in Scheme I for the example of the triosephosphate isomerase (TIM) reaction.As the reaction proceeds from the ground state to the transition state, negative charge accumulates on the carbonyl oxygen, as reflected by the Ϸ10-unit increase in the pK a of this group. [The pK a of the carbonyl oxygen in the ground state is estimated to be Ϫ2 to 0; the pK a of the enol hydroxyl in a fully enolic transition state is estimated to be Ϸ10 (1).] The hydrogen bond (H bond) from a histidine residue of TIM to the carbonyl oxygen can be strengthened by this charge buildup (depicted by the darker dots in Scheme I). However, to obtain a rate enhancement relative to the solution reaction, the strengthening of an H bond to an enzymatic group in the course of a reaction must be greater than the strengthening of the corresponding H bond to water.Could the environment of the enzyme active site increase the change in H bond strength accompanying charge rearrangements relative to that in water? To address this question, we used the aprotic organic solvent dimethyl sulfoxide (DMSO) as a crude mimic of the active site environment and investigated the energetics of the intramolecular H bond in a series of substituted salicylate monoanions in both DMSO and water. There is a larger increase in H bond strength in DMSO than in water as the pK a values of the H bonding groups are varied. We suggest that a substantial amount of catalysis can be obtained by enzymes from the greater strengthening of H bonds accompanying charge rearrangements in nonaqueous environments than in aqueous solutions. MATERIALS AND METHODS Materials.The indicators 2,6-di-tert-butyl-4-nitrophenol and 9-carboxym...

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Section: Discussionmentioning

confidence: 77%

“…DMSO may therefore provide a crude mimic for the environment in an enzymatic interior, despite its high bulk dielectric constant. In general, larger Brønsted slopes for H bonds are observed in nonaqueous solutions than in water (10,11,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)36).…”

Section: Origins Of the Larger Brønsted Slopes Of H Bonding Inmentioning

confidence: 99%

The change in hydrogen bond strength accompanying charge rearrangement: Implications for enzymatic catalysis

Shan

Herschlag²

1996

Proc. Natl. Acad. Sci. U.S.A.

186

197

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“…16 It is evident that the enhanced acidity of the thiourea proton by the introduction of an electron withdrawing substituent causes the anion binding extremely strong. 16,17 As can be seen from Table 1 and Fig. 2, the changes in the absorption spectra are clearly anion dependent.…”

Section: Resultsmentioning

confidence: 63%

“…[4][5][6][7] In design and fabrication of new anion receptors for applications in aprotic media [8][9][10][11] , the (thio)urea group as hydrogen bond donor has recently drawn much interest as a functional group for neutral receptors to recognize mono-and dicarboxylate anions, halide anions, sulfate, as well as dihydrogenphosphate etc. 6c,9-17 Wilcox et al 17 have recently shown substituent effects in arylthiourea upon binding with a zwitterionic sulfonic acid in chloroform. In their study, some of the aryl(thio)ureas with a nitro group were found to show changes in their UV-Vis spectra upon complexation.…”

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confidence: 99%

Anion Sensing by a Thiourea Based Chromoionophore via Hydrogen Bonding

et al. 1998

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Development of chromogenic receptors for biologically important substrates is one of the current research topics in analytical chemistry and biochemistry. A wide variety of chromoionophores for cations such as alkali and alkaline-earth metal ions 1 as well as amines 2,3 have been reported. In contrast, only a few chromoionophores have been reported for the colorimetric determination of anions in solution. [4][5][6][7] In design and fabrication of new anion receptors for applications in aprotic media [8][9][10][11] , the (thio)urea group as hydrogen bond donor has recently drawn much interest as a functional group for neutral receptors to recognize mono-and dicarboxylate anions, halide anions, sulfate, as well as dihydrogenphosphate etc. 6c,9-17 Wilcox et al. 17 have recently shown substituent effects in arylthiourea upon binding with a zwitterionic sulfonic acid in chloroform. In their study, some of the aryl(thio)ureas with a nitro group were found to show changes in their UV-Vis spectra upon complexation. However, these spectral changes were only utilized to assess association strengths, and no further studies of these materials as chromogenic anion receptors have been reported.We now report herein a very simple anion receptor 1 in which a p-nitrophenyl group is linked to a methylthiourea moiety. In this type of donor-acceptor chromophore, the electronic excitation is mostly accompanied by a charge transfer from donor nitrogen of the thiourea to acceptor substituent (-NO 2 ) of the chromophore.18 Thus, the excited state would be more strongly stabilized by anion binding, resulting in a bathochromic shift in the absorption maxima (l max ). Introducing the electron withdrawing substituent enhances the acidity of thiourea moiety, receptor 1 strongly binds with anions to produce an effective color change in aprotic media. Experimental Chemicals and instrumentsAll guest anions were commercially available as tetrabutylammonium salts and purified by recrystallization as described elsewhere. 16 Spectrometric grade acetonitrile was purchased from Nacalai Tesque, Inc.(Kyoto, Japan), and dried over molecular sieves 3A. 1 H NMR spectra were obtained on a JEOL a-500 spectrometer (500 MHz; JEOL DATUM, Tokyo, Japan). All chemical shifts values (d) are reported in parts per million (ppm), using the residual solvent signal (2.49) of DMSO-d 6 as reference. Absorption spectra were recorded at 25˚C with a Hitachi U-3000 spectrophotometer (Hitachi, Ltd., Tokyo, Japan). (1) p-Nitroaniline (2.0 g, 14 mmol) was dissolved in ethanol-triethylamine (dried over molecular sieves 4A, 220 ml) and a solution of methyl isothiocyanate (9.1 g, 124 mmol) in ethanol (5 ml) was added slowly. The reaction solution was stirred for 47 h at 80˚C, and then the solvent was evaporated. Repeated recrystallization from ethanol gave the product as pale yellow crystals (0.30 g; 10% H, 4.29; N, 19.89; S, 15.18. Found: C, 45.42; H, 4.28; N, 19.60; S, 14.88. Synthesis of N-methyl-N´-(4-nitrophenyl)thiourea Results and DiscussionThe spectral characteristics o...

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“…[8][9][10][11][12][13][14][15] We have recently reported that selective colorimetry and fluorometry of anions are feasible by introducing chromogenic and fluorogenic transducers into the thiourea moiety with an electronically conjugated structure. [16][17][18] If the anion recognition is performed by solvent extraction, the function of these anion receptors would be applicable to various separation and sensing systems such as membrane transport and optode analysis.…”

mentioning

confidence: 99%

Efficient Ion-Pair Extraction of Potassium Chloride from Aqueous Phase into Nitrobenzene Containing Dicyclohexyl-18-crown-6 as Cation Binder and Diphenylthiourea as Anion Binder

et al. 1999

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Ion-pair recognition of cationic and anionic guest species by bifunctional receptors is a current topic in molecular recognition chemistry. [1][2][3][4][5] Recently Beer et al. have designed novel rhenium(I) bipyridyl amide crown ether receptors and shown that these receptors complexed to form K + Cl -ion pairs in which complexation of crown ether moiety with K + cooperated in the binding of Cl -in organic solution. 6 Reinhoudt et al. have also shown that calix[4]arenes bearing urea moieties behave as bifunctional receptors in which the anion binding is controlled by the complex formation of tetraester binding site with alkali metal cations in chloroform. 7 In these receptors, the amide moieties functioned as anion recognition sites through hydrogenbonding interactions.Thiourea moiety has also shown to be an effective binding site to recognize anions such as mono-and dicarboxylate, halide, sulfate, and dihydrogenphosphate anions through hydrogen-bonding interaction. [8][9][10][11][12][13][14][15] We have recently reported that selective colorimetry and fluorometry of anions are feasible by introducing chromogenic and fluorogenic transducers into the thiourea moiety with an electronically conjugated structure. [16][17][18] If the anion recognition is performed by solvent extraction, the function of these anion receptors would be applicable to various separation and sensing systems such as membrane transport and optode analysis. [19][20][21][22][23][24] To prove this feasibility, we report herein an efficient synergistic effect of a thiourea receptor for an ion-pair extraction of potassium salts by dicyclohexyl-18-crown-6 (DC18C6) through hydrogen-bonding interaction. DC18C6 is well known as a specific binder for potassium cation. 25 In combination with the ion pair extraction of potassium salts by DC18C6, the extraction behavior of nitrate, bromide, chloride, and acetate ions from aqueous into nitrobenzene solution with a simple ion receptor, diphenylthiourea (DPTU), have been examined. Interestingly, the hydrophilic chloride ion is effectively extracted into the organic solution in the presence of DPTU. The importance of hydrogenbonding interaction for this extraction system is clarified by 1 H NMR analysis in the present study. ExperimentalReagents Diphenylthiourea receptor, DPTU, was purchased from Wako Pure Chemical Co., Ltd. DC18C6 was obtained from Tokyo Chemical Industry Co., Ltd. Science, Tohoku University, Aoba, Japan In combination with an ion pair extraction of potassium salts by dicyclohexyl-18-crown-6 (DC18C6), extraction behavior of anions with a diphenylthiourea (DPTU) from aqueous phase into nitrobenzene has been examined. The extraction selectivity of potassium salts follows a Hofmeister series: NO3 ->Br ->Cl ->OAc -. The extractability of KCl by DC18C6 is significantly enhanced upon the addition of DPTU in organic solution. The slope analysis of the extraction equilibrium reveals a 1:1 complex formation between DPTU and Cl -. The hydrogen-bonding interaction of DPTU with Cl -is confirmed by ...

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Experimental and theoretical studies of substituent effects in hydrogen bond based molecular recognition of a zwitterion by substituted arylureas

Cited by 123 publications

References 13 publications

The change in hydrogen bond strength accompanying charge rearrangement: Implications for enzymatic catalysis

The change in hydrogen bond strength accompanying charge rearrangement: Implications for enzymatic catalysis

Anion Sensing by a Thiourea Based Chromoionophore via Hydrogen Bonding

Efficient Ion-Pair Extraction of Potassium Chloride from Aqueous Phase into Nitrobenzene Containing Dicyclohexyl-18-crown-6 as Cation Binder and Diphenylthiourea as Anion Binder

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