Modulation of pK<sub>a</sub> by cyclodextrins; subtle structural changes induce spectacularly different behaviors

Nowak, Paweł Mateusz; Woźniakiewicz, Michał; Mitoraj, Mariusz P.; Garnysz, Magdalena; Kościelniak, Paweł

doi:10.1039/c5ra14032c

Cited by 19 publications

(16 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increase in the guest p K a value (Δp K a >0) is generally observed for cation‐receptor or hydrogen bond‐acceptor host (such as cucurbiturils, p ‐sulfonated calixarenes,, and carboxylatopillarenes) which guest have an affinity for cations), while a decrease in the p K a value is commonly found with anion‐receptor or hydrogen bond‐donor hosts (such as cyclodextrins (with exceptions), which have an affinity for anions) . A molecular dynamics protocol has been developed for calculating the pH‐dependent binding free energies for CB[7] .…”

Section: Ground State Acid‐base Equilibriamentioning

confidence: 99%

Cucurbit[n]uril Host‐Guest Complexes of Acids, Photoacids, and Super Photoacids

Macartney

2017

Israel Journal of Chemistry

View full text Add to dashboard Cite

The supramolecular chemistry of host‐guest complexes of cucurbit[n]urils (CB[n]) with acidic guests in the ground (HG+) and excited states (HG+*) are reviewed. The effects of CB[n] complexation on the guests’ pKa and/or pKa* values are related to relative binding constants and host‐guest structures of the acid form of the guest and its conjugate base. Included are carbon acids, guests of biological and medicinal interest, dyes and related polyaromatic guests, and other organic and organometallic guests. The applications of the pKa shifts to the solubility, stability, and bioavailabilty of drug molecules, the stability and enhanced spectral properties of dyes, and in pH‐induced self‐sorting, micelle formation, host‐guest shuttling, and controlled guest release, are discussed.

show abstract

Section: Ground State Acid‐base Equilibriamentioning

confidence: 99%

Cucurbit[n]uril Host‐Guest Complexes of Acids, Photoacids, and Super Photoacids

Macartney

2017

Israel Journal of Chemistry

View full text Add to dashboard Cite

show abstract

“…Preceding studies on the interactions of W with several CD derivatives have been taken into consideration while planning the experiments for this part [ 9 , 10 , 11 , 12 ]. Accordingly, new derivatives of β-CD were selected, namely Ac-β-CD and HE-β-CD ( Chart S1, Supporting Information ).…”

Section: Resultsmentioning

confidence: 99%

“…The rationale behind our selection arises from the presence of additional hydroxyl or carbonyl functional groups that could enhance interactions with W. Unfortunately, both macrocycles gave weak or no interactions with W, as monitored by UV-visible absorption measurements at pH 3 and 9 ( Figure S1, Supporting Information ). However, the previously examined derivative Me-β-CD gave the highest binding constants [ 10 ], as illustrated in Figure 1 . The lack of encapsulation by other β-CD cages is due to size mismatch, more flexible cages and weaker non-bonded interactions with hydroxycoumarin derivatives [ 3 ].…”

Section: Resultsmentioning

confidence: 99%

Sequestration Effect on the Open-Cyclic Switchable Property of Warfarin Induced by Cyclodextrin: Time-Resolved Fluorescence Study

Al-Dubaili

Saleh

2017

Molecules

View full text Add to dashboard Cite

The excited-state lifetimes of the anticoagulant drug warfarin (W) in water and in the absence and presence of methyl-β-cyclodextrins (Me-β-CD) were recorded using time-resolved fluorescence measurements. Selective excitation of the open and cyclic protonated isomers of W were acquired with laser emitting diodes (LED) producing 320 and 280 nm excitation pulses, respectively. Formation of the inclusion complex was checked by UV-visible absorption spectroscopy, and the values of binding constants (2.9 × 103 M–1 and 4.2 × 102 M−1 for protonated and deprotonated forms, respectively) were extracted from the spectrophotometric data. Both absorption and time-resolved fluorescence results established that the interior of the macromolecular host binds preferentially the open protonated form, red shifts the maximum of its absorption of light at ~305 nm, extends its excited-state lifetime, and decreases its emission quantum yield (ФF). Collectively, sequestration of the open guest molecules decreases markedly their radiative rate constants (kr), likely due to formation of hydrogen-bonded complexes in both the ground and excited states. Due to lack of interactions, no change was observed in the excited-state lifetime of the cyclic form in the presence of Me-β-CD. The host also increases the excited-state lifetime and ФF of the drug deprotonated form (W−). These later findings could be attributed to the increased rigidity inside the cavity of Me-β-CD. The pKa values extracted from the variations of the UV-visible absorption spectra of W versus the pH of aqueous solution showed that the open isomer is more acidic in both ground and excited states. The positive shifts in pKa values induced by three derivatives of cyclodextrins: HE-β-CD, Ac-β-CD, and Me-β-CD supported the preferential binding of these hosts to open isomers over cyclic.

show abstract

“…. In theory, at this pH two different mechanisms may contribute to enantioseparation, the one employing different binding affinities of enantiomers for CD, and the second one, following from different p K a shifts induced by complexation with CD . Various CDs were tested as the potential chiral selectors, differing in structural features such as size, substitution type and substitution degree.…”

Section: The Values Of Validation Parameters Obtained For MC 3‐mmc Amentioning

confidence: 99%

“…A. At such a low pH value only the mechanism based on different binding affinities plays the role in enantioseparation, since the enantiomers are equally (totally) ionized despite possibly different p K a shifts induced by complexation .…”

Section: The Values Of Validation Parameters Obtained For MC 3‐mmc Amentioning

confidence: 99%

Simultaneous enantioseparation of methcathinone and two isomeric methylmethcathinones using capillary electrophoresis assisted by 2‐hydroxyethyl‐β‐cyclodextrin

et al. 2018

Self Cite

View full text Add to dashboard Cite

Methcathinone (ephedrone), 4-methylmethcathinone (mephedrone), and 3-methylmethcathinone (metaphedrone) are toxicologically-important cathinone derivatives used commonly as designer drugs. In this work we show the first method allowing to separate simultaneously all these molecules in a chiral medium, ensuring good resolution between all enantiomers. Eight cyclodextrins have been tested as potential chiral selectors, the best results were obtained with 2-hydroxyethyl-β-cyclodextrin, unreported so far for efficient separation of cathinones. After optimization, the method was calibrated and validated with and without the use of internal standard. The addition of standard improved an overall repeatability and precision, the use of electrophoretic mobility ratio was especially favorable (RSD < 1%). It was demonstrated that the method may be easily extended by introducing the additional cathinone-related drugs to the sample, maintaining satisfactory separation efficiency.

show abstract

Modulation of pK_a by cyclodextrins; subtle structural changes induce spectacularly different behaviors

Abstract: Supramolecular acidity tuning: it is shown that minor structural changes of guests and hosts molecules may be of great importance for the complexation-induced pKa shifts and their temperature dependency.

Cited by 19 publications

References 25 publications

Cucurbit[n]uril Host‐Guest Complexes of Acids, Photoacids, and Super Photoacids

Cucurbit[n]uril Host‐Guest Complexes of Acids, Photoacids, and Super Photoacids

Sequestration Effect on the Open-Cyclic Switchable Property of Warfarin Induced by Cyclodextrin: Time-Resolved Fluorescence Study

Simultaneous enantioseparation of methcathinone and two isomeric methylmethcathinones using capillary electrophoresis assisted by 2‐hydroxyethyl‐β‐cyclodextrin

Contact Info

Product

Resources

About

Modulation of pKa by cyclodextrins; subtle structural changes induce spectacularly different behaviors

Abstract: Supramolecular acidity tuning: it is shown that minor structural changes of guests and hosts molecules may be of great importance for the complexation-induced pKa shifts and their temperature dependency.

Cited by 19 publications

References 25 publications

Cucurbit[n]uril Host‐Guest Complexes of Acids, Photoacids, and Super Photoacids

Cucurbit[n]uril Host‐Guest Complexes of Acids, Photoacids, and Super Photoacids

Sequestration Effect on the Open-Cyclic Switchable Property of Warfarin Induced by Cyclodextrin: Time-Resolved Fluorescence Study

Simultaneous enantioseparation of methcathinone and two isomeric methylmethcathinones using capillary electrophoresis assisted by 2‐hydroxyethyl‐β‐cyclodextrin

Contact Info

Product

Resources

About

Modulation of pK_a by cyclodextrins; subtle structural changes induce spectacularly different behaviors