scholarly journals Thermodynamic properties of hydroxypropyl-β-cyclodextrin/guest interaction: a survey of recent studies

2021 ◽  
Author(s):  
Federica D’Aria ◽  
Bruno Pagano ◽  
Concetta Giancola
Keyword(s):  
Thermodynamic Properties ◽  
Isothermal Titration Calorimetry ◽  
Binding Constant ◽  
State Of The Art ◽  
Titration Calorimetry ◽  
Routes Of Administration ◽  
Binding Stoichiometry ◽  
Low Toxicity ◽  
The Stability ◽  
Thermodynamic Factors

AbstractFor many years, cyclodextrins (CDs) have been the object of attention for their capability of improving the stability, solubility and bioavailability of numerous molecules of interest, including drugs and nutraceuticals. They have low toxicity and for this reason have been employed for different routes of administration, including oral, ocular, nasal and parenteral. Among them, the hydroxypropyl-β-cyclodextrin (HP-β-CD) is the least toxic. Several physicochemical methodologies have been employed for studying cyclodextrin/guest interaction, but isothermal titration calorimetry (ITC) is the only one capable of simultaneously providing the binding constant, ΔH°, ΔS°, ΔG° and the binding stoichiometry. Here, we present the state of the art of ITC studies applied to HP-β-CD/guest complexes, discussing selected publications of the last five years, highlighting the thermodynamic factors that are decisive for optimal encapsulation.

scholarly journals Extracellular DNA Impedes the Transport of Vancomycin in Staphylococcus epidermidis Biofilms Preexposed to Subinhibitory Concentrations of Vancomycin

2014 ◽  
Vol 58 (12) ◽  
pp. 7273-7282 ◽  
Author(s):  
Natalya Doroshenko ◽  
Boo Shan Tseng ◽  
Robert P. Howlin ◽  
Jill Deacon ◽  
Julian A. Wharton ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Isothermal Titration Calorimetry ◽  
Staphylococcus Epidermidis ◽  
Binding Constant ◽  
Biofilm Formation ◽  
Potential Role ◽  
Extracellular Dna ◽  
Titration Calorimetry ◽  
Orthopedic Implant ◽  
Content Type

ABSTRACTStaphylococcus epidermidisbiofilm formation is responsible for the persistence of orthopedic implant infections. Previous studies have shown that exposure ofS. epidermidisbiofilms to sub-MICs of antibiotics induced an increased level of biofilm persistence. BODIPY FL-vancomycin (a fluorescent vancomycin conjugate) and confocal microscopy were used to show that the penetration of vancomycin through sub-MIC-vancomycin-treatedS. epidermidisbiofilms was impeded compared to that of control, untreated biofilms. Further experiments showed an increase in the extracellular DNA (eDNA) concentration in biofilms preexposed to sub-MIC vancomycin, suggesting a potential role for eDNA in the hindrance of vancomycin activity. Exogenously added,S. epidermidisDNA increased the planktonic vancomycin MIC and protected biofilm cells from lethal vancomycin concentrations. Finally, isothermal titration calorimetry (ITC) revealed that the binding constant of DNA and vancomycin was 100-fold higher than the previously reported binding constant of vancomycin and its intended cellulard-Ala-d-Ala peptide target. This study provides an explanation of the eDNA-based mechanism of antibiotic tolerance in sub-MIC-vancomycin-treatedS. epidermidisbiofilms, which might be an important factor for the persistence of biofilm infections.

scholarly journals Discovery of a Novel General Anesthetic Chemotype Using High-throughput Screening

2015 ◽  
Vol 122 (2) ◽  
pp. 325-333 ◽  
Author(s):  
Andrew R. McKinstry-Wu ◽  
Weiming Bu ◽  
Ganesha Rai ◽  
Wendy A. Lea ◽  
Brian P. Weiser ◽  
...  
Keyword(s):  
Isothermal Titration Calorimetry ◽  
High Throughput ◽  
High Throughput Screening ◽  
Medicinal Chemistry ◽  
Titration Calorimetry ◽  
Anesthetic Activity ◽  
High Throughput Screen ◽  
High Potency ◽  
Low Toxicity ◽  
Anesthetic Potency

Abstract Background: The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures. Methods: Using a novel high-throughput screen employing the fluorescent anesthetic 1-aminoanthracene and apoferritin as a surrogate for on-pathway anesthetic protein target(s), we screened a 350,000 compound library for competition with 1-aminoanthracene–apoferritin binding. Hit compounds meeting structural criteria had their binding affinities for apoferritin quantified with isothermal titration calorimetry and were tested for γ-aminobutyric acid type A receptor binding using a flunitrazepam binding assay. Chemotypes with a strong presence in the top 700 and exhibiting activity via isothermal titration calorimetry were selected for medicinal chemistry optimization including testing for anesthetic potency and toxicity in an in vivo Xenopus laevis tadpole assay. Compounds with low toxicity and high potency were tested for anesthetic potency in mice. Results: From an initial chemical library of more than 350,000 compounds, we identified 2,600 compounds that potently inhibited 1-aminoanthracene binding to apoferritin. A subset of compounds chosen by structural criteria (700) was successfully reconfirmed using the initial assay. Based on a strong presence in both the initial and secondary screens the 6-phenylpyridazin-3(2H)-one chemotype was assessed for anesthetic activity in tadpoles. Medicinal chemistry efforts identified four compounds with high potency and low toxicity in tadpoles, two were found to be effective novel anesthetics in mice. Conclusion: The authors demonstrate the first use of a high-throughput screen to successfully identify a novel anesthetic chemotype and show mammalian anesthetic activity for members of that chemotype.

Thermodynamic Analysis of Chitooligosaccharide Binding to Urtica dioica agglutinin by Isothermal Titration Calorimetry

1999 ◽  
Vol 19 (5) ◽  
pp. 411-419 ◽  
Author(s):  
Samiksha Katiyar ◽  
E. J. M. Van Damme ◽  
Willy J. Peumans ◽  
Avadhesha Surolia
Keyword(s):  
Thermodynamic Parameters ◽  
Isothermal Titration Calorimetry ◽  
Thermodynamic Analysis ◽  
Binding Constant ◽  
Urtica Dioica ◽  
Titration Calorimetry ◽  
Sugar Residue ◽  
Binding Enthalpy ◽  
Urtica Dioica Agglutinin

UDA (Urtica dioica agglutinin) contains two hevein like domains with two non-identical interacting sites and is specific for chitooligosaccharides. The binding of chitooligosaccharides to UDA was studied by Isothermal Titration Calorimetry. Each site is composed of three subsites, each binding to a sugar residue. Thermodynamic parameters obtained show that while chitobiose has two independent non-interacting sites, chitotriose, chitotetrose and chitopentose have two interacting sites on each monomer of UDA. Values of binding enthalpy (ΔH) increase almost by a factor of 7 in going from chitobiose to chitotriose indicating the existence of three subsites in the combining site of UDA. The binding constant for chitotetrose and chitopentose increase without any further enhancement in the values of ΔH indicating that for oligomers larger than chitotriose interaction is favoured entropically.

scholarly journals Evaluation of the stability of cucurbit[8]uril-based ternary host−guest complexation in physiological environment and the fabrication of a supramolecular theranostic nanomedicine

2021 ◽  
Author(s):  
Han Wu ◽  
Zuobing Chen ◽  
Shaolong Qi ◽  
Bing Bai ◽  
Jiajun Ye ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Isothermal Titration Calorimetry ◽  
Titration Calorimetry ◽  
Resonance Spectroscopy ◽  
Vis Spectroscopy ◽  
Non Covalent Interactions ◽  
The Stability ◽  
Covalent Interactions

Abstract PurposeTo evaluate the stability of cucurbit[8]uril-based 1:1:1 ternary host−guest complexation in physiological environment for the fabrication of supramolecular theranostics with promising potentials in precise cancer imaging and therapy. MethodsThe host−guest complexation between cucurbit[8]uril (CB[8]), 4,4′-bipyridinium, and napththyl guest was fully studied using various characterizations, including nuclear magnetic resonance spectroscopy ( 1 H NMR), ultraviolet-visible (UV-vis) spectroscopy, isothermal titration calorimetry (ITC). The association constants of this ternary complex were determined using isothermal titration calorimetry. The stability of the non-covalent interactions and self-assemblies form from this molecular recognition was confirmed by UV-vis spectroscopy and dynamic light scattering (DLS). A supramolecular nanomedicine was constructed on the basis of this 1:1:1 ternary recognition, and its in vitro and in vivo anticancer efficacy were thoroughly evaluated. Positron emission tomography (PET) imaging was used to monitor the delivery and biodistribution of the supramolecular nanomedicine. ResultsVarious experiments confirmed that the ternary complexation between 4,4′-bipyridinium, and napththyl derivative and CB[8] was stable in physiological environment, including phosphate buffered solution and cell culture medium. Supramolecular nanomedicine (SNM@DOX) encapsulating a neutral anticancer drug (doxrubincin, DOX) was prepared based on this molecular recognition that linked the hydrophobic poly(ε-caprolactone) chain and hydrophilic polyethylene glycol segment. The non-covalent interactions guaranteed the stability of SNM@DOX during blood circulation and promoted its tumor accumulation by taking advantage of the enhanced permeability and retention effect, thus greatly improving the anti-tumor efficacy as compared with the free drug. ConclusionArising from the host-enhanced charge-transfer interactions, the CB[8]-based ternary recognition was stable enough in physiological environment, which was suitable for the fabrication of supramolecular nanotheranostics showing promising potentials in precise cancer diagnosis and therapy.

scholarly journals Evaluation of the stability of cucurbit[8]uril-based ternary host−guest complexation in physiological environment and the fabrication of a supramolecular theranostic nanomedicine

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Han Wu ◽  
Zuobing Chen ◽  
Shaolong Qi ◽  
Bing Bai ◽  
Jiajun Ye ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Isothermal Titration Calorimetry ◽  
Disease Diagnosis ◽  
Titration Calorimetry ◽  
Resonance Spectroscopy ◽  
Diagnosis And Therapy ◽  
Vis Spectroscopy ◽  
Non Covalent Interactions ◽  
The Stability ◽  
Covalent Interactions

Abstract Background Supramolecular theranostics have exhibited promising potentials in disease diagnosis and therapy by taking advantages of the dynamic and reversible nature of non-covalent interactions. It is extremely important to figure out the stability of the driving forces in physiological environment for the preparation of theranostic systems. Methods The host−guest complexation between cucurbit[8]uril (CB[8]), 4,4′-bipyridinium, and napththyl guest was fully studied using various characterizations, including nuclear magnetic resonance spectroscopy, ultraviolet–visible (UV–vis) spectroscopy, isothermal titration calorimetry (ITC). The association constants of this ternary complex were determined using isothermal titration calorimetry. The stability of the non-covalent interactions and self-assemblies form from this molecular recognition was confirmed by UV–vis spectroscopy and dynamic light scattering (DLS). A supramolecular nanomedicine was constructed on the basis of this 1:1:1 ternary recognition, and its in vitro and in vivo anticancer efficacy were thoroughly evaluated. Positron emission tomography (PET) imaging was used to monitor the delivery and biodistribution of the supramolecular nanomedicine. Results Various experiments confirmed that the ternary complexation between 4,4′-bipyridinium, and napththyl derivative and CB[8] was stable in physiological environment, including phosphate buffered solution and cell culture medium. Supramolecular nanomedicine (SNM@DOX) encapsulating a neutral anticancer drug (doxrubincin, DOX) was prepared based on this molecular recognition that linked the hydrophobic poly(ε-caprolactone) chain and hydrophilic polyethylene glycol segment. The non-covalent interactions guaranteed the stability of SNM@DOX during blood circulation and promoted its tumor accumulation by taking advantage of the enhanced permeability and retention effect, thus greatly improving the anti-tumor efficacy as compared with the free drug. Conclusion Arising from the host-enhanced charge-transfer interactions, the CB[8]-based ternary recognition was stable enough in physiological environment, which was suitable for the fabrication of supramolecular nanotheranostics showing promising potentials in precise cancer diagnosis and therapy. Graphic Abstract

scholarly journals Calorimetric Studies of Melanotransferrin (p97) and Its Interaction with Iron

2005 ◽  
Vol 280 (16) ◽  
pp. 15735-15741 ◽  
Author(s):  
A. Louise Creagh ◽  
Jacqueline W. C. Tiong ◽  
Mei Mei Tian ◽  
Charles A. Haynes ◽  
Wilfred A. Jefferies
Keyword(s):  
Differential Scanning Calorimetry ◽  
Isothermal Titration Calorimetry ◽  
Binding Constant ◽  
Direct Determination ◽  
Molar Ratio ◽  
Titration Calorimetry ◽  
Iron Binding ◽  
Scanning Calorimetry ◽  
Binding Characteristics ◽  
Apparent Binding Constant

The mammalian molecule melanotransferrin (mTf), also called p97, is a member of the transferrin family of molecules. It exists in both secreted and glycosylphosphatidylinositol-anchored forms and is thought to play a role in angiogenesis and in transporting iron across the blood brain barrier. The binding affinity of iron to this molecule has not been formally established. Here, the binding of ferric ion (chelated with a 2-fold molar ratio of nitrilotriacetate) to mTf has been studied using isothermal titration calorimetry and differential scanning calorimetry. One iron-binding site was determined for mTf with similar binding characteristics to other transferrins. In the absence of bicarbonate, binding occurs quickly with an apparent association constant of 2.6 × 107m–1at 25 °C. The presence of bicarbonate introduces kinetic effects that prevent direct determination of the apparent binding constant by isothermal titration calorimetry. Differential scanning calorimetry thermograms of mTf unfolding in the presence and absence of iron were therefore used to determine the apparent binding constant in the bicarbonate-containing system; at pH 7.5 and 25 °C, iron binding occurs in a 1:1 ratio with aKappof 4.4 × 1017m–1. This affinity is intermediate between the high and low affinity lobes of transferrin and suggests that mTf is likely to play a significant role in iron transport where the high affinity lobe of transferrin is occupied or where transferrin is in proportionally low concentrations.

scholarly journals Inhibition study of adenosine deaminase by caffeine using spectroscopy and isothermal titration calorimetry.

2003 ◽  
Vol 50 (3) ◽  
pp. 849-855 ◽  
Author(s):  
A A Saboury ◽  
A Divsalar ◽  
G Ataie ◽  
M Amanlou ◽  
A A Moosavi-Movahedi ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Isothermal Titration Calorimetry ◽  
Binding Constant ◽  
Titration Calorimetry ◽  
Uv Spectrophotometry ◽  
Positive Dependence ◽  
Sodium Phosphate Buffer ◽  
Fitting Method ◽  
Kinetic And Thermodynamic Studies

Kinetic and thermodynamic studies were made on the effect of caffeine on the activity of adenosine deaminase in 50 mM sodium phosphate buffer, pH 7.5, using UV spectrophotometry and isothermal titration calorimetry (ITC). An uncompetitive inhibition was observed for caffeine. A graphical fitting method was used for determination of binding constant and enthalpy of inhibitor binding by using isothermal titration microcalorimetry data. The dissociation-binding constant is equal to 350 microM by the microcalorimetry method, which agrees well with the value of 342 microM for the inhibition constant that was obtained from the spectroscopy method. Positive dependence of caffeine binding on temperature indicates a hydrophobic interaction.

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