Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions

Since several years the inclusion of organic compounds (guests) within the hydrophobic cavity (host) of cyclodextrins (CDs) has been the subject of many investigations. Interestingly, the formation of inclusion complexes could affect the properties of the guest molecules and, for example, the influence of the delivery system can be a method to improve/change the photochemical behavior of the guest. In particular, very recent studies have shown the protective role of CDs preventing the degradation of the encapsulated guest. Starting from this consideration, in this work, only the structure and complexation mode of the inclusion complexes involving 4-thiothymidine (S4TdR, a known photosensitizer) and five CDs, namely 2-hydroxypropyl-α-cyclodextrin (2-HP-α-CD), 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), 2-hydroxypropyl-γ-cyclodextrin (2-HP-γ-CD), heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB CD) and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB CD) were investigated by different spectroscopic techniques (UV–vis, FTIR–ATR, 1H NMR) and cyclic voltammetry analysis (CV). This work is necessary for a prospective research on the photoreactivity of S4TdR in aqueous environment and in the presence of CDs to prevent its degradation under irradiation. UV–vis, FTIR–ATR and CV measurements suggested the formation of supramolecular structures involving the employed CDs and mainly the pyrimidine ring of S4TdR. 1H NMR analyses confirmed such indication, unveiling the presence of inclusion complexes. The strongest and deepest interactions were suggested when TRIMEB and DIMEB CDs were studied. The S4TdR affinity towards CDs was also evaluated by using the Benesi–Hildebrand (B–H) equation at 25 °C employing CV and 1H NMR methods. The stoichiometry of the interaction was also inferred and it appears to be 1:1 for all examined CDs.

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Intermolecular interactions in inclusion complexes

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273314093267 ◽

2014 ◽

Vol 70 (a1) ◽

pp. C673-C673

Author(s):

Kinga Suwinska

Keyword(s):

Inclusion Complexes ◽

Biological Systems ◽

Water Soluble ◽

The European Union ◽

Guest Molecules ◽

Development Fund ◽

Natural Systems ◽

Design And Synthesis ◽

Drug Molecules ◽

Solvent Molecules

The whole range of interactions can be found between host and guest in supramolecular assemblies from ion-ion interactions, ion-dipole interactions, dipol-dipol interactions through hydrogen bonding, cation-π interactions, π-π stacking to van der Waals forces. Additionally, the same interactions exist between the supramolecular complex and its surrounding, i.e. solvent molecules, neighboring complexes, gases, etc. Recently the interest of scientists in the field of supramolecular chemistry is focused on design and synthesis of water-soluble synthetic macrocyclic ligands which are good receptors for biologically important guest molecules and can mimic the models of biological systems. Studying such complexes may provide new insight into the mechanisms of the formation of similar natural systems and as a consequence will help in better understanding the processes which occur in biological systems and in developing new materials with specific properties and functions. In this presentation the interactions which are stabilizing inclusion complexes of calix[n]arenes and cyclodextrins (host molecules) with guest molecules of biological interest, especially drug molecules will be discussed. This research was partly financed by the European Union within the European Regional Development Fund (POIG.01.01.02-14-102/09)

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Tuning of the Cavity of Water-Soluble Thiacalix[4]arene for the Control of Inclusion Ability Toward Water-Miscible Organic Molecules

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20041080 ◽

2004 ◽

Vol 69 (5) ◽

pp. 1080-1096 ◽

Cited By ~ 5

Author(s):

Noriyoshi Kon ◽

Nobuhiko Iki ◽

Yuichiro Sano ◽

Satoshi Ogawa ◽

Chizuko Kabuto ◽

...

Keyword(s):

Guest Molecule ◽

Organic Molecules ◽

Hydrophobic Effect ◽

Binding Constants ◽

Water Soluble ◽

Main Role ◽

Diethyl Ketone ◽

Guest Molecules ◽

X Ray ◽

H Nmr

Inclusion abilities of water-soluble thiacalix[4]arenetetrasulfonate (3) and mono-O-carboxymethylated derivatives 5 and 6 toward water-miscible organic molecules such as alcohols, ketones, and nitriles in water were investigated by 1H NMR. The limit chemical shift change of the guest upon inclusion in the host suggested that the hosts regioselectively encapsulate the guests from the side of aliphatic moiety. Large guests such as pentan-1-ol showed folding of the alkyl chain to be included inside the cavity. On the other hand, mono-O-substituted 6 included a guest molecule less deep in the cavity than 3 did. Binding constants (K) of 3 toward guest molecules increased with hydrophobicity of the guest, suggesting that hydrophobic effect plays a main role for the complexation. On the contrary, mono-O-carboxymethyl derivatives 5 and 6 showed the opposite dependency of stability on hydrophobicity; higher affinities toward less hydrophobic guests. Among the guests examined, the smallest entities such as CH3OH and CH3CN were best included in 5 with the highest binding constant ever reported (K > 102 M-1). It was concluded that introduction of the carboxymethyl group into one of the phenolic OH of thiacalix[4]arene led to tuning of the cavity shape for stereospecific inclusion of small guests. The tuning of cavity by the O-alkylation was actually confirmed by X-ray crystal analysis of a complex of 5 with diethyl ketone.

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Enantioselective Recognition of Chiral Guests by the Water-Soluble Chiral Keplerate {Mo132} Spherical Capsule with 30 Inner Lactate Ligands

10.26434/chemrxiv.8847923.v1 ◽

2019 ◽

Author(s):

Nancy Watfa ◽

Weimin Xuan ◽

Zoe Sinclair ◽

Robert Pow ◽

Yousef Abul-Haija ◽

...

Keyword(s):

Aqueous Solution ◽

Chiral Recognition ◽

Association Constants ◽

Water Soluble ◽

Enantioselective Recognition ◽

H Nmr ◽

Dosy Nmr ◽

Spherical Capsule ◽

Surface Pores ◽

Guest Chemistry

Investigations of chiral host guest chemistry are important to explore recognition in confined environments. Here, by synthesizing water-soluble chiral porous nanocapsule based on the inorganic metal-oxo Keplerate-type cluster, {Mo132} with chiral lactate ligands with the composition [Mo132O372(H2O)72(x-Lactate)30]42- (x = D or L), it was possible to study the interaction with a chiral guest, L/D-carnitine and (R/S)-2-butanol in aqueous solution. The enantioselective recognition was studied by quantitative 1H NMR and 1H DOSY NMR which highlighted that the chiral recognition is regulated by two distinct sites. Differences in the association constants (K) of L- and D-carnitine, which, due to their charge, are generally restricted from entering the interior of the host, are observed, indicating that their recognition predominantly occurs at the surface pores of the structure. Conversely, a larger difference in association constants (KS/KR = 3) is observed for recognition within the capsule interior of (R)- and (S)-2-butanol.

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NMR Studies of the Inclusion Complexes Between Ezetimibe and Cyclodextrins

Revista de Chimie ◽

10.37358/rc.18.7.6427 ◽

2018 ◽

Vol 69 (7) ◽

pp. 1838-1841

Author(s):

Hajnal Kelemen ◽

Angella Csillag ◽

Bela Noszal ◽

Gabor Orgovan

Keyword(s):

Inclusion Complex ◽

Inclusion Complexes ◽

Water Solubility ◽

Solution Nmr ◽

Spectroscopic Techniques ◽

Nmr Studies ◽

The Poor ◽

Poor Water Solubility

Ezetimibe, the antihyperlipidemic drug of poor bioavailability was complexed with native and derivatized cyclodextrins.The complexes were characterized in terms stability, stoichiometry and structure using various 1D and 2D solution NMR spectroscopic techniques. The complexes were found to be of moderate stability (logK[3). The least stable inclusion complex is formed with b-cyclodextrin, while the ezetimibe-methylated-b--cyclodextrin has a 7-fold higher stability. The results can be useful to improve the poor water-solubility and the concomitant bioavailability of ezetimibe.

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Improved thermally stable oligoetherols from 6-aminouracil, ethylene carbonate and boric acid

Open Chemistry ◽

10.1515/chem-2019-0118 ◽

2019 ◽

Vol 17 (1) ◽

pp. 1080-1086

Author(s):

Elżbieta Chmiel-Szukiewicz

Keyword(s):

Thermal Stability ◽

Thermal Properties ◽

Boric Acid ◽

Ethylene Carbonate ◽

Pyrimidine Ring ◽

Polyurethane Foams ◽

High Thermal Stability ◽

H Nmr ◽

Maldi Tof ◽

Instrumental Methods

AbstractSyntheses of oligoetherols with a 1,3-pyrimidine ring and boron atoms using 6-aminouracil, ethylene carbonate and boric acid has been proposed. The structure of the obtained products were determined by instrumental methods (IR, 1H-NMR and MALDI-ToF spectra). The physicochemical and thermal properties of oligoetherols were examined. The products were characterized by high thermal stability. Based on the tests performed, it was found that oligoetherols obtained from 6-aminouracil, boric acid and ethylene carbonate are suitable for the manufacturing of polyurethane foams with improved thermal stability and reduced flammability.

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Direct photoreactive immobilization of water-soluble phospholipid polymers on substrates in an aqueous environment

Colloids and Surfaces B Biointerfaces ◽

10.1016/j.colsurfb.2020.111507 ◽

2021 ◽

Vol 199 ◽

pp. 111507

Author(s):

Kyoko Fukazawa ◽

Kazushi Tsuji ◽

Yuuki Inoue ◽

Kazuhiko Ishihara

Keyword(s):

Water Soluble ◽

Aqueous Environment

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Water-soluble β-aminobisulfonate building blocks for pH and Cu2+ indicators

RSC Advances ◽

10.1039/c6ra17791c ◽

2016 ◽

Vol 6 (88) ◽

pp. 84712-84721 ◽

Cited By ~ 5

Author(s):

Maria A. Cardona ◽

Marina Kveder ◽

Ulrich Baisch ◽

Michael R. Probert ◽

David C. Magri

Keyword(s):

Nmr Spectroscopy ◽

Building Blocks ◽

Water Soluble ◽

Visible Absorption ◽

H Nmr ◽

Uv Visible

Two phenyl β-aminobisulfonate ligands characterised by UV-visible absorption, EPR and 1H NMR spectroscopy exhibit evidence for binding with Cu2+ in water and methanol.

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Synthesis and Guest-Binding Properties of pH/Reduction Dual-Responsive Cyclophane Dimer

Molecules ◽

10.3390/molecules26113097 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3097

Author(s):

Osamu Hayashida ◽

Yudai Tanaka ◽

Takaaki Miyazaki

Keyword(s):

Electrostatic Interaction ◽

Disulfide Bonds ◽

Water Soluble ◽

Guest Molecules ◽

Binding Behavior ◽

Dual Responsive ◽

Guest Binding ◽

Basic Solutions ◽

Ph Conditions ◽

Almost All

A water-soluble cyclophane dimer having two disulfide groups as a reduction-responsive cleavable bond as well as several acidic and basic functional groups as a pH-responsive ionizable group 1 was successfully synthesized. It was found that 1 showed pH-dependent guest-binding behavior. That is, 1 strongly bound an anionic guest, 6-p-toluidinonaphthalene-2-sulfonate (TNS) with binding constant (K/M−1) for 1:1 host-guest complexes of 9.6 × 104 M−1 at pH 3.8, which was larger than those at pH 7.4 and 10.7 (6.0 × 104 and 2.4 × 104 M−1, respectively), indicating a favorable electrostatic interaction between anionic guest and net cationic 1. What is more, release of the entrapped guest molecules by 1 was easily controlled by pH stimulus. Large favorable enthalpies (ΔH) for formation of host-guest complexes were obtained under the pH conditions employed, suggesting that electrostatic interaction between anionic TNS and 1 was the most important driving force for host-guest complexation. Such contributions of ΔH for formation of host-guest complexes decreased along with increased pH values from acidic to basic solutions. Upon addition of dithiothreitol (DTT) as a reducing reagent to an aqueous PBS buffer (pH 7.4) containing 1 and TNS, the fluorescence intensity originating from the bound guest molecules decreased gradually. A treatment of 1 with DTT gave 2, having less guest-binding affinity by the cleavage of disulfide bonds of 1. Consequently, almost all entrapped guest molecules by 1 were released from the host. Moreover, such reduction-responsive cleavage of 1 and release of bound guest molecules was performed more rapidly in aqueous buffer at pH 10.7.

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Diorganotin(iv) benzyldithiocarbamate complexes: synthesis, characterization, and thermal and cytotoxicity study

Open Chemistry ◽

10.1515/chem-2020-0037 ◽

2020 ◽

Vol 18 (1) ◽

pp. 453-462

Author(s):

Jerry O. Adeyemi ◽

Damian C. Onwudiwe ◽

Nirasha Nundkumar ◽

Moganavelli Singh

Keyword(s):

Cell Lines ◽

Human Tumor ◽

Complexation Reaction ◽

Spectroscopic Techniques ◽

X Ray Diffraction ◽

Human Tumor Cell Lines ◽

H Nmr ◽

Cytotoxicity Studies ◽

Final Residue ◽

Mcf 7

AbstractAmmonium benzyldithiocarbamate, represented as NH4L, was prepared and used in the complexation reaction involving three organotin(iv) salts, represented as R2SnCl2 (R = CH3, C4H9, and C6H5). The structures of the synthesized complexes [(CH3)2SnL2] (1), [(C4H9)2SnL2] (2), and [(C6H5)2SnL2] (3) were established using various spectroscopic techniques (Fourier transform infrared spectroscopy, 1H NMR, 13C NMR, and 119Sn NMR) and elemental analysis. Thermal decomposition of the complexes using thermogravimetric analysis under nitrogen showed no definite pathway in the pattern of the complexes even though they are structurally related. X-ray diffraction studies of the final residue showed a common diffraction pattern for the complexes and confirmed SnS as the product of the thermal treatment. Cytotoxicity studies of these complexes against the human tumor cell lines (HeLa and MCF-7) compared favorably with the used standard 5-fluorouracil drug, with complexes 2 and 3 showing very good activity toward the used cell lines.

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Probing Inclusion Complexes of Pentoxifylline and Pralidoxim inside Cyclic Oligosaccharides by Physicochemical Methodologies

Zeitschrift für Physikalische Chemie ◽

10.1515/zpch-2017-1020 ◽

2019 ◽

Vol 233 (8) ◽

pp. 1109-1127

Author(s):

Biraj Kumar Barman ◽

Kanak Roy ◽

Mahendra Nath Roy

Keyword(s):

Surface Tension ◽

Free Energy ◽

Inclusion Complexes ◽

Apparent Molar Volume ◽

Nmr Spectra ◽

Drug Delivery Systems ◽

Surface Tension Data ◽

H Nmr ◽

Ft Ir ◽

Inclusion Phenomena

Abstract Structurally different Molecules namely Pentoxifylline and Pralidoxim were chosen along with α-cyclodextrin and β-cyclodextrin to study host-guest inclusion phenomena. The formations of host guest inclusion complexes were confirmed by studying 1H-NMR spectra, FT-IR spectra, apparent molar volume and viscosity co-efficient. The stabilities of inclusion complexes were compared calculating the binding constant from UV-VIS spectroscopic study. The 1:1 stoichiometry of the inclusion complexes were also determined by analysing the Jobs plot and surface tension data. The values for Gibbs’ free energy were found negative for both the processes. Based on all the above experiments the inclusion processes were found feasible for both the compounds. These types of inclusion complexes are of high interest in the field of research and industry as these are used as drug delivery systems.

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