Choong Leol Yoo - Academia.edu (original) (raw)

Papers by Choong Leol Yoo

Research paper thumbnail of Synthesis and biological activity of 2-(4,5-dihydroisoxazol-5-yl)-1,3,4-oxadiazoles

Bioorganic Medicinal Chemistry Letters, Sep 1, 2009

Acid hydrazides were coupled with acrylic acid derivatives and cyclodehydration gave 1,3,4-oxadia... more Acid hydrazides were coupled with acrylic acid derivatives and cyclodehydration gave 1,3,4-oxadiazoles. Lastly, in-situ nitrile oxide formation from aryl oximes treated with sodium hypochlorite, and subsequent 1,3-dipolar cycloaddition to the exomethylene moiety delivered 2-(4,5-dihydroisoxazol-5-yl)-1,3,4-oxadiazoles. This library was evaluated in a high-throughput screen at Dow AgroSciences. Several compounds were active against fungal pathogens and pest insects.

Research paper thumbnail of ChemInform Abstract: Synthesis and Biological Activity of 2-(4,5-Dihydroisoxazol-5-yl)-1,3,4-oxadiazoles

Research paper thumbnail of Potent s-cis -Locked Bithiazole Correctors of ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy ⊥

J Med Chem, 2008

N-(5-(2-(5-Chloro-2-methoxyphenylamino)thiazol-4-yl)-4-methylthiazol-2-yl)pivalamide 1 (compound ... more N-(5-(2-(5-Chloro-2-methoxyphenylamino)thiazol-4-yl)-4-methylthiazol-2-yl)pivalamide 1 (compound 15Jf) was found previously to correct defective cellular processing of the cystic fibrosis protein ∆F508-CFTR. Eight C4′-C5 C,C-bond-controlling bithiazole analogues of 1 were designed, synthesized, and evaluated to establish that constraining rotation about the bithiazole-tethering has a significant effect on corrector activity. For example, constraining the C4′-C5 bithiazole tether in the s-cis conformation [N-(2-(5-chloro-2methoxyphenylamino)-7,8-dihydro-6H-cyclohepta[1,2-d:3,4-d′]bithiazole-2′-yl)pivalamide, 29] results in improved corrector activity. Heteroatom placement in the bithaizole core is also critical as evidenced by the decisive loss of corrector activity with s-cis constrained N-(2-(5-chloro-2-methoxyphenylamino)-5,6-dihydro-4H-cyclohepta[1,2-d:3,4-d′]bithiazole-2′-yl)pivalamide 33. In addition, computational models were utilized to examine the conformational preferences for select model systems. Following our analysis, the "s-cislocked" cycloheptathiazolothiazole 29 was found to be the most potent bithiazole corrector, with an IC 50 of ∼450 nM.

Research paper thumbnail of A Novel Chiral Resolving Reagent, Bis(( S )-Mandelic acid)-3-nitrophthalate, for Amlodipine Racemate Resolution: Scalable Synthesis and Resolution Process

Organic Process Research & Development, 2009

Research paper thumbnail of Synthesis of 2H-Pyrroles via the 1,3-Dipolar Cycloaddition Reaction of Nitrile Ylides with Acrylamides

ChemInform, 2006

Pyrrole derivatives R 0120 Synthesis of 2H-Pyrroles via the 1,3-Dipolar Cycloaddition Reaction of... more Pyrrole derivatives R 0120 Synthesis of 2H-Pyrroles via the 1,3-Dipolar Cycloaddition Reaction of Nitrile Ylides with Acrylamides.-The reaction is investigated with respect to the acrylamide substitution pattern and benzimidoyl chloride equilibration.-(YOO, C. L.;

Research paper thumbnail of Constrained bithiazoles: small molecule correctors of defective ΔF508-CFTR protein trafficking

Journal of medicinal chemistry, Jan 14, 2014

Conformationally constrained bithiazoles were previously found to have improved efficacy over non... more Conformationally constrained bithiazoles were previously found to have improved efficacy over nonconstrained bithiazoles for correction of defective cellular processing of the ΔF508 mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. In this study, two sets of constrained bithiazoles were designed, synthesized, and tested in vitro using ΔF508-CFTR expressing epithelial cells. The SAR data demonstrated that modulating the constraining ring size between 7- versus 8-membered in these constrained bithiazole correctors did not significantly enhance their potency (IC50), but strongly affected maximum efficacy (Vmax), with constrained bithiazoles 9e and 10c increasing Vmax by 1.5-fold compared to benchmark bithiazole corr4a. The data suggest that the 7- and 8-membered constrained ring bithiazoles are similar in their ability to accommodate the requisite geometric constraints during protein binding.

Research paper thumbnail of Stannous Chloride in Alcohol:  A One-Pot Conversion of 2-Nitro- N -arylbenzamides to 2,3-Dihydro-1 H -quinazoline-4-ones

The Journal of Organic Chemistry, 2005

Research paper thumbnail of Aminodeoxychorismate Synthase Inhibitors from One-Bead One-Compound Combinatorial Libraries:  “Staged” Inhibitor Design

Journal of Medicinal Chemistry, 2006

Research paper thumbnail of Chemical Inhibition of the Mitochondrial Division Dynamin Reveals Its Role in Bax/Bak-Dependent Mitochondrial Outer Membrane Permeabilization

Developmental Cell, 2008

Mitochondrial fusion and division play important roles in the regulation of apoptosis. Mitochondr... more Mitochondrial fusion and division play important roles in the regulation of apoptosis. Mitochondrial fusion proteins attenuate apoptosis by inhibiting release of cytochrome c from mitochondria, in part by controlling cristae structures. Mitochondrial division promotes apoptosis by an unknown mechanism. We addressed how division proteins regulate apoptosis using inhibitors of mitochondrial division identified in a chemical screen. The most efficacious inhibitor, mdivi-1 (for mitochondrial division inhibitor) attenuates mitochondrial division in yeast and mammalian cells by selectively inhibiting the mitochondrial division dynamin. In cells, mdivi-1 retards apoptosis by inhibiting mitochondrial outer membrane permeabilization. In vitro, mdivi-1 potently blocks Bid-activated Bax/Bak-dependent cytochrome c release from mitochondria. These data indicate the mitochondrial division dynamin directly regulates mitochondrial outer membrane permeabilization independent of Drp1-mediated division. Our findings raise the interesting possibility that mdivi-1 represents a novel class of therapeutics for stroke, myocardial infarction, and neurodegenerative diseases.

Research paper thumbnail of Design and synthesis of a hybrid potentiator–corrector agonist of the cystic fibrosis mutant protein ΔF508-CFTR

Bioorganic & Medicinal Chemistry Letters, 2010

A developing therapy of cystic fibrosis caused by the DF508 mutation in CFTR employs correction o... more A developing therapy of cystic fibrosis caused by the DF508 mutation in CFTR employs correction of defective CFTR chloride channel gating by a 'potentiator' and of defective CFTR protein folding by a 'corrector'. Based on SAR data for phenylglycine-type potentiators and bithiazole correctors, we designed a hybrid molecule incorporating an enzymatic hydrolysable linker to deliver the potentiator (PG01) fragment 2 and the corrector (Corr-4a) fragment 13. The hybrid molecule 14 contained PG01-OH and Corr-4a-linker-CO 2 H moieties, linked with an ethylene glycol spacer through an ester bond. The potentiator 2 and corrector 13 fragments (after cleavage) had low micromolar potency for restoration of DF508-CFTR channel gating and cellular processing, respectively. Cleavage of hybrid molecule 14 by intestinal enzymes under physiological conditions produced the active potentiator 2 and corrector fragments 13, providing proof-of-concept for small-molecule potentiator-corrector hybrids as a single drug therapy for CF caused by the DF508 mutation.

Research paper thumbnail of 4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing

Bioorganic & Medicinal Chemistry Letters, 2008

The synthesis and DF508-CFTR corrector activity of a 148-member methylbithiazole-based library ar... more The synthesis and DF508-CFTR corrector activity of a 148-member methylbithiazole-based library are reported. Synthetic routes were devised and optimized to generate methylbithiazole analogs in four steps. Corrector potency and efficacy were assayed using epithelial cells expressing human DF508-CFTR. These structure-activity data establish that the bithiazole substructure plays a critical function; eight novel methylbithiazole correctors were identified with low micromolar potencies.

Research paper thumbnail of Tweezer-Type Neutral Carrier-Based Calcium-Selective Membrane Electrode with Drastically Reduced Anionic Interference

Analytical Chemistry, 2002

A new calcium-selective ionophore N,N-dioctyl-3alpha,12alpha-bis(N-heptyl-N-methylcarbamoyl-metho... more A new calcium-selective ionophore N,N-dioctyl-3alpha,12alpha-bis(N-heptyl-N-methylcarbamoyl-methoxyacetamidoacetoxy)-5beta-cholan-24-amide (denoted as BACA), was synthesized, and its potentiometric performance has been evaluated in comparison with that of the best known calcium-selective neutral carriers, ETH 129 and ETH 1001. The 1H NMR spectra of BACA titrated with Ca(SCN)2 suggest that BACA forms a 1:1 complex, tweezing a calcium ion between the two parallel diamide groups substituted on a rigid bile acid frame. The calcium-selective membrane based on BACA was less selective to calcium (log K(Ca2+ j)POT = -4.2, -4.2, -4.6, and -4.8, respectively, for j = Mg2+, Li+, Na+, and K+) than those based on ETH 129 (log K(Ca2+ j)POT = -4.4, -4.3, -5.4, and -5.4, respectively, in the same order) and ETH 1001 (log K(Ca2+ j)POT = -4.4, -4.4, -5.4, and -5.4), implying that BACA forms a weaker calcium complex than the other two ETH compounds. In our experimental conditions, potentiometrically determined complex formation constants of calcium-selective neutral carriers (log beta(Ca2+ L)) were 15.2, 14.0, and 8.6 for ETH 129, ETH 1001, and BACA, respectively. A slightly reduced calcium selectivity of BACA, however, affects the anionic interference-free calcium-selective membrane; the BACA-based membrane exhibits a Nernstian response up to 10(-1) M Ca2+ in the presence of lipophilic anions (e.g., SCN-, ClO4-, salicylate, and I-) and anionic surfactant, whereas the ETH 129- and ETH 1001-based ones suffer from serious anionic interference showing a curvature or leveled off response over about 10(-4) M. It was demonstrated that such a trade off does not affect the analytical performance of BACA-based electrode in most applications, including clinical analysis.

Research paper thumbnail of Potentiometric Evaluation of Solvent Polymeric Carbonate-Selective Membranes Based on Molecular Tweezer-Type Neutral Carriers

Analytical Chemistry, 2000

Potentiometric properties of the ion-selective electrodes) based on highly plasticized PVC membra... more Potentiometric properties of the ion-selective electrodes) based on highly plasticized PVC membranes doped with the carbonate-selective cholic acid (CA) derivatives have been measured. The carbonate-selective neutral carriers have been prepared by coupling one to three trifluoroacetobenzoyl (TFAB) groups to a cholic acid derivative which has three hydroxyl linkers lining on the C3, C7, and C12 positions of its rigid steroidal ring structure. The membranes based on cholic acid derivatives with two TFABs [3,7-bis(TFAB)CA, 3,12-bis(TFAB)CA, and 7,12-bis(T-FAB)CA] exhibited remarkably improved carbonate selectivity, indicating that the bis(FAB)CAs behave like molecular tweezers for the carbonate ion. For example, 3,12-bis(TFAB)CA resulted in 10-300-fold-enhanced carbonate selectivity over other anions (e.g., salicylate, ClO4-, SCN-, (HPO4)2-, NO3-, NO2-, Br-, and Cl-) compared to that of the neutral carriers with a single TFAB group. The distances between the carbonate binding centers of bis(TFAB)CAs, i.e., the carbonyl carbons of the two TFAB groups, are in the 7.3-7.9-A range at the AM1 level semiempirical calculation, which is too far for the carbonate ion to form direct covalent bonding. The fast atom bombardment mass spectra of bis(TFAB)CAs show that significant fractions of the compounds are either mono- or dihydrated before complexing the carbonate ion. These findings seem to suggest that bis(TFAB)CAs recognize the incoming carbonate ion by forming both covalent and hydrogen bonding between the hydrated and unhydrated TFAB groups. The analytical utility of the carbonate-selective electrode based on 3,12-bis(TFAB)-CA has been demonstrated by measuring the total carbon dioxide in human serum in the presence of lipophilic anion interferents, e.g., salicylate.

Research paper thumbnail of Potent s-cis-Locked Bithiazole Correctors of ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy⊥

Journal of medicinal …, 2008

┴ X-ray crystallographic data of N-(2-(5-chloro-2-methoxyphenylamino)-7,8-dihydro-6H-cyclohepta-[... more ┴ X-ray crystallographic data of N-(2-(5-chloro-2-methoxyphenylamino)-7,8-dihydro-6H-cyclohepta-[1,2-d:3,4-d']bithiazole-2'-yl)pivalamide (C 21 H 23 ClN 4 O 2 S 2) were submitted to the Cambridge Crystallographic Data Centre (deposition number CCDC687310).

Research paper thumbnail of Synthesis and biological activity of 2-(4,5-dihydroisoxazol-5-yl)-1,3,4-oxadiazoles

Bioorganic Medicinal Chemistry Letters, Sep 1, 2009

Acid hydrazides were coupled with acrylic acid derivatives and cyclodehydration gave 1,3,4-oxadia... more Acid hydrazides were coupled with acrylic acid derivatives and cyclodehydration gave 1,3,4-oxadiazoles. Lastly, in-situ nitrile oxide formation from aryl oximes treated with sodium hypochlorite, and subsequent 1,3-dipolar cycloaddition to the exomethylene moiety delivered 2-(4,5-dihydroisoxazol-5-yl)-1,3,4-oxadiazoles. This library was evaluated in a high-throughput screen at Dow AgroSciences. Several compounds were active against fungal pathogens and pest insects.

Research paper thumbnail of ChemInform Abstract: Synthesis and Biological Activity of 2-(4,5-Dihydroisoxazol-5-yl)-1,3,4-oxadiazoles

Research paper thumbnail of Potent s-cis -Locked Bithiazole Correctors of ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy ⊥

J Med Chem, 2008

N-(5-(2-(5-Chloro-2-methoxyphenylamino)thiazol-4-yl)-4-methylthiazol-2-yl)pivalamide 1 (compound ... more N-(5-(2-(5-Chloro-2-methoxyphenylamino)thiazol-4-yl)-4-methylthiazol-2-yl)pivalamide 1 (compound 15Jf) was found previously to correct defective cellular processing of the cystic fibrosis protein ∆F508-CFTR. Eight C4′-C5 C,C-bond-controlling bithiazole analogues of 1 were designed, synthesized, and evaluated to establish that constraining rotation about the bithiazole-tethering has a significant effect on corrector activity. For example, constraining the C4′-C5 bithiazole tether in the s-cis conformation [N-(2-(5-chloro-2methoxyphenylamino)-7,8-dihydro-6H-cyclohepta[1,2-d:3,4-d′]bithiazole-2′-yl)pivalamide, 29] results in improved corrector activity. Heteroatom placement in the bithaizole core is also critical as evidenced by the decisive loss of corrector activity with s-cis constrained N-(2-(5-chloro-2-methoxyphenylamino)-5,6-dihydro-4H-cyclohepta[1,2-d:3,4-d′]bithiazole-2′-yl)pivalamide 33. In addition, computational models were utilized to examine the conformational preferences for select model systems. Following our analysis, the "s-cislocked" cycloheptathiazolothiazole 29 was found to be the most potent bithiazole corrector, with an IC 50 of ∼450 nM.

Research paper thumbnail of A Novel Chiral Resolving Reagent, Bis(( S )-Mandelic acid)-3-nitrophthalate, for Amlodipine Racemate Resolution: Scalable Synthesis and Resolution Process

Organic Process Research & Development, 2009

Research paper thumbnail of Synthesis of 2H-Pyrroles via the 1,3-Dipolar Cycloaddition Reaction of Nitrile Ylides with Acrylamides

ChemInform, 2006

Pyrrole derivatives R 0120 Synthesis of 2H-Pyrroles via the 1,3-Dipolar Cycloaddition Reaction of... more Pyrrole derivatives R 0120 Synthesis of 2H-Pyrroles via the 1,3-Dipolar Cycloaddition Reaction of Nitrile Ylides with Acrylamides.-The reaction is investigated with respect to the acrylamide substitution pattern and benzimidoyl chloride equilibration.-(YOO, C. L.;

Research paper thumbnail of Constrained bithiazoles: small molecule correctors of defective ΔF508-CFTR protein trafficking

Journal of medicinal chemistry, Jan 14, 2014

Conformationally constrained bithiazoles were previously found to have improved efficacy over non... more Conformationally constrained bithiazoles were previously found to have improved efficacy over nonconstrained bithiazoles for correction of defective cellular processing of the ΔF508 mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. In this study, two sets of constrained bithiazoles were designed, synthesized, and tested in vitro using ΔF508-CFTR expressing epithelial cells. The SAR data demonstrated that modulating the constraining ring size between 7- versus 8-membered in these constrained bithiazole correctors did not significantly enhance their potency (IC50), but strongly affected maximum efficacy (Vmax), with constrained bithiazoles 9e and 10c increasing Vmax by 1.5-fold compared to benchmark bithiazole corr4a. The data suggest that the 7- and 8-membered constrained ring bithiazoles are similar in their ability to accommodate the requisite geometric constraints during protein binding.

Research paper thumbnail of Stannous Chloride in Alcohol:  A One-Pot Conversion of 2-Nitro- N -arylbenzamides to 2,3-Dihydro-1 H -quinazoline-4-ones

The Journal of Organic Chemistry, 2005

Research paper thumbnail of Aminodeoxychorismate Synthase Inhibitors from One-Bead One-Compound Combinatorial Libraries:  “Staged” Inhibitor Design

Journal of Medicinal Chemistry, 2006

Research paper thumbnail of Chemical Inhibition of the Mitochondrial Division Dynamin Reveals Its Role in Bax/Bak-Dependent Mitochondrial Outer Membrane Permeabilization

Developmental Cell, 2008

Mitochondrial fusion and division play important roles in the regulation of apoptosis. Mitochondr... more Mitochondrial fusion and division play important roles in the regulation of apoptosis. Mitochondrial fusion proteins attenuate apoptosis by inhibiting release of cytochrome c from mitochondria, in part by controlling cristae structures. Mitochondrial division promotes apoptosis by an unknown mechanism. We addressed how division proteins regulate apoptosis using inhibitors of mitochondrial division identified in a chemical screen. The most efficacious inhibitor, mdivi-1 (for mitochondrial division inhibitor) attenuates mitochondrial division in yeast and mammalian cells by selectively inhibiting the mitochondrial division dynamin. In cells, mdivi-1 retards apoptosis by inhibiting mitochondrial outer membrane permeabilization. In vitro, mdivi-1 potently blocks Bid-activated Bax/Bak-dependent cytochrome c release from mitochondria. These data indicate the mitochondrial division dynamin directly regulates mitochondrial outer membrane permeabilization independent of Drp1-mediated division. Our findings raise the interesting possibility that mdivi-1 represents a novel class of therapeutics for stroke, myocardial infarction, and neurodegenerative diseases.

Research paper thumbnail of Design and synthesis of a hybrid potentiator–corrector agonist of the cystic fibrosis mutant protein ΔF508-CFTR

Bioorganic & Medicinal Chemistry Letters, 2010

A developing therapy of cystic fibrosis caused by the DF508 mutation in CFTR employs correction o... more A developing therapy of cystic fibrosis caused by the DF508 mutation in CFTR employs correction of defective CFTR chloride channel gating by a 'potentiator' and of defective CFTR protein folding by a 'corrector'. Based on SAR data for phenylglycine-type potentiators and bithiazole correctors, we designed a hybrid molecule incorporating an enzymatic hydrolysable linker to deliver the potentiator (PG01) fragment 2 and the corrector (Corr-4a) fragment 13. The hybrid molecule 14 contained PG01-OH and Corr-4a-linker-CO 2 H moieties, linked with an ethylene glycol spacer through an ester bond. The potentiator 2 and corrector 13 fragments (after cleavage) had low micromolar potency for restoration of DF508-CFTR channel gating and cellular processing, respectively. Cleavage of hybrid molecule 14 by intestinal enzymes under physiological conditions produced the active potentiator 2 and corrector fragments 13, providing proof-of-concept for small-molecule potentiator-corrector hybrids as a single drug therapy for CF caused by the DF508 mutation.

Research paper thumbnail of 4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing

Bioorganic & Medicinal Chemistry Letters, 2008

The synthesis and DF508-CFTR corrector activity of a 148-member methylbithiazole-based library ar... more The synthesis and DF508-CFTR corrector activity of a 148-member methylbithiazole-based library are reported. Synthetic routes were devised and optimized to generate methylbithiazole analogs in four steps. Corrector potency and efficacy were assayed using epithelial cells expressing human DF508-CFTR. These structure-activity data establish that the bithiazole substructure plays a critical function; eight novel methylbithiazole correctors were identified with low micromolar potencies.

Research paper thumbnail of Tweezer-Type Neutral Carrier-Based Calcium-Selective Membrane Electrode with Drastically Reduced Anionic Interference

Analytical Chemistry, 2002

A new calcium-selective ionophore N,N-dioctyl-3alpha,12alpha-bis(N-heptyl-N-methylcarbamoyl-metho... more A new calcium-selective ionophore N,N-dioctyl-3alpha,12alpha-bis(N-heptyl-N-methylcarbamoyl-methoxyacetamidoacetoxy)-5beta-cholan-24-amide (denoted as BACA), was synthesized, and its potentiometric performance has been evaluated in comparison with that of the best known calcium-selective neutral carriers, ETH 129 and ETH 1001. The 1H NMR spectra of BACA titrated with Ca(SCN)2 suggest that BACA forms a 1:1 complex, tweezing a calcium ion between the two parallel diamide groups substituted on a rigid bile acid frame. The calcium-selective membrane based on BACA was less selective to calcium (log K(Ca2+ j)POT = -4.2, -4.2, -4.6, and -4.8, respectively, for j = Mg2+, Li+, Na+, and K+) than those based on ETH 129 (log K(Ca2+ j)POT = -4.4, -4.3, -5.4, and -5.4, respectively, in the same order) and ETH 1001 (log K(Ca2+ j)POT = -4.4, -4.4, -5.4, and -5.4), implying that BACA forms a weaker calcium complex than the other two ETH compounds. In our experimental conditions, potentiometrically determined complex formation constants of calcium-selective neutral carriers (log beta(Ca2+ L)) were 15.2, 14.0, and 8.6 for ETH 129, ETH 1001, and BACA, respectively. A slightly reduced calcium selectivity of BACA, however, affects the anionic interference-free calcium-selective membrane; the BACA-based membrane exhibits a Nernstian response up to 10(-1) M Ca2+ in the presence of lipophilic anions (e.g., SCN-, ClO4-, salicylate, and I-) and anionic surfactant, whereas the ETH 129- and ETH 1001-based ones suffer from serious anionic interference showing a curvature or leveled off response over about 10(-4) M. It was demonstrated that such a trade off does not affect the analytical performance of BACA-based electrode in most applications, including clinical analysis.

Research paper thumbnail of Potentiometric Evaluation of Solvent Polymeric Carbonate-Selective Membranes Based on Molecular Tweezer-Type Neutral Carriers

Analytical Chemistry, 2000

Potentiometric properties of the ion-selective electrodes) based on highly plasticized PVC membra... more Potentiometric properties of the ion-selective electrodes) based on highly plasticized PVC membranes doped with the carbonate-selective cholic acid (CA) derivatives have been measured. The carbonate-selective neutral carriers have been prepared by coupling one to three trifluoroacetobenzoyl (TFAB) groups to a cholic acid derivative which has three hydroxyl linkers lining on the C3, C7, and C12 positions of its rigid steroidal ring structure. The membranes based on cholic acid derivatives with two TFABs [3,7-bis(TFAB)CA, 3,12-bis(TFAB)CA, and 7,12-bis(T-FAB)CA] exhibited remarkably improved carbonate selectivity, indicating that the bis(FAB)CAs behave like molecular tweezers for the carbonate ion. For example, 3,12-bis(TFAB)CA resulted in 10-300-fold-enhanced carbonate selectivity over other anions (e.g., salicylate, ClO4-, SCN-, (HPO4)2-, NO3-, NO2-, Br-, and Cl-) compared to that of the neutral carriers with a single TFAB group. The distances between the carbonate binding centers of bis(TFAB)CAs, i.e., the carbonyl carbons of the two TFAB groups, are in the 7.3-7.9-A range at the AM1 level semiempirical calculation, which is too far for the carbonate ion to form direct covalent bonding. The fast atom bombardment mass spectra of bis(TFAB)CAs show that significant fractions of the compounds are either mono- or dihydrated before complexing the carbonate ion. These findings seem to suggest that bis(TFAB)CAs recognize the incoming carbonate ion by forming both covalent and hydrogen bonding between the hydrated and unhydrated TFAB groups. The analytical utility of the carbonate-selective electrode based on 3,12-bis(TFAB)-CA has been demonstrated by measuring the total carbon dioxide in human serum in the presence of lipophilic anion interferents, e.g., salicylate.

Research paper thumbnail of Potent s-cis-Locked Bithiazole Correctors of ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy⊥

Journal of medicinal …, 2008

┴ X-ray crystallographic data of N-(2-(5-chloro-2-methoxyphenylamino)-7,8-dihydro-6H-cyclohepta-[... more ┴ X-ray crystallographic data of N-(2-(5-chloro-2-methoxyphenylamino)-7,8-dihydro-6H-cyclohepta-[1,2-d:3,4-d']bithiazole-2'-yl)pivalamide (C 21 H 23 ClN 4 O 2 S 2) were submitted to the Cambridge Crystallographic Data Centre (deposition number CCDC687310).