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The understanding of the relationship between molecular structure and the thermodynamics of host-guest binding is essential for the rational design of the applications of inclusion complexes. To obtain insight into the factors governing the driving force of complex formation in aqueous solutions, the encapsulation of five pharmaceutically important protoberberine alkaloids was studied in sulfobutylether-β-cyclodextrin having on average 6.4 degrees of substitution (SBE6.4βCD). Spectrophotometric, fluorescence spectroscopic, and isothermal calorimetric measurements showed 1:1 complexation in dilute solutions. From 1.92 × 104 M−1, about an eight-fold decrease of the association constant was observed in the series of berberine ≈ coptisine >> palmatine > epiberberine > dehydrocorydaline. The embedment of these alkaloids in the SBE6.4βCD cavity was entropy-controlled with mildly negative enthalpy contributions. These findings suggest that the stabilization of the examined complexes arises primarily from the hydrophobic interaction between the constituents. The more than three orders of magnitude smaller association constants of protoberberine alkaloids with SBE6.4βCD than with cucurbit[7]uril, a host having similar cavity size, originates from the much smaller exothermicity of the confinement in the former macrocycle.

The inclusion of protonated (-)-tetrahydropalmatine (THP+) and dehydrocorydaline (DHC+), natural alkaloids, in the cavity of cucurbit[7]uril was monitored in real time by a spectrofluorimetric method in water at various temperatures. Both guests produced 1 : 1 complexes in enthalpy controlled processes without any detectable intermediates. The tight entrance of CB7 imposed substantial steric hindrance for encapsulation making the entry into the host several orders of magnitude slower than diffusion. Despite the ∼6 kJ mol-1 lower activation enthalpy, the rate constant of THP+ ingression into CB7 was about 44-fold smaller at 298 K than that of DHC+ as a consequence of the considerably negative activation entropy of the former binding. The egression rates of the two studied alkaloids differed to a much lesser extent because the lower energy barrier of THP+ release was almost compensated by the unfavourable activation entropy. In comparison with the kinetics of the reversible confinement of the palmatine parent compound, the presence of the methyl substituent on the aromatic heterocyclic ring in DHC+ barely modified the rate constant of entry into CB7 but caused about 10-fold increase in the dissociation rate at 298 K.

Very little information is available on the kinetics of the self-assembly and dissociation of optically silent building blocks despite the importance of such data in the rational design of tailor-made host���guest systems. We introduce here a novel time-resolved method that enables the simultaneous determination of complex formation and complex dissociation rate constants for inclusion-type host���guest complexes. The simultaneous analyte indicator binding assay (SBA) gives also direct access to binding affinities, thus largely simplifying the experimental procedure for a full kinetic and thermodynamic characterisation of host���guest systems.

Seven dimethyl-substituted optically active pyridino-18-crown-6 ethers containing various substituents at position 4 of the pyridine ring were studied with regards to the electron-donating and -withdrawing effects of substituents on enantiomeric recognition. In order to compile this set of compounds, we prepared four novel pyridino-18-crown-6 ethers, including an intermediate of a new synthetic route for a formerly reported crown ether. The discriminating ability of these pyridino-crown ethers with C2-symmetry toward the enantiomers of protonated primary amines was examined by isothermal titration calorimetry.

Both thermodynamic and kinetic insights are needed for a proper analysis of association and dissociation processes of host–guest interactions. However, kinetic descriptions of supramolecular systems are scarce in the literature because suitable experimental protocols are lacking. We introduce here three time-resolved methods that allow for convenient determination of kinetic rate constants of spectroscopically silent or even insoluble guests with the macrocyclic cucurbit[n]uril family and human serum albumin (HSA) protein as representative hosts.

The release of two organic guests from cucurbit[7]uril (CB7) was selectively monitored by the stopped‐flow method in aqueous solutions of inorganic salts to reveal the mechanistic picture in detail. Two contrasting mechanisms were identified: The symmetric dicationic 2,7‐dimethyldiazapyrenium shows a cation‐independent complex dissociation mechanism coupled to deceleration of the ingression in the presence of alkali and alkaline earth cations (Mn+) due to competitive formation of CB7–Mn+ complexes. A much richer, unprecedented kinetic behaviour was observed for the ingression and egression of the monocationic and non‐symmetric berberine (B+). The formation of ternary complex B+–CB7–Mn+ was unambiguously revealed. A difference of more than two orders of magnitude was found in the equilibrium constants of Mn+ binding to B+–CB7 inclusion complex. Large cations, such as K+ and Ba2+, also promoted B+ expulsion from the ternary complex in a bimolecular process. This study reveals a previously hidden mechanistic picture and motivates systematic kinetic investigations of other host–guest systems., Contrasting mechanisms: Stopped‐flow studies on the release of two organic guests from cucurbit[7]uril (CB7) in aqueous solutions of inorganic salts revealed two contrasting mechanisms. Whereas metal cations Mn+ promote the release of berberine (B+) from CB7 in a multistep process, the expulsion of dicationic dye 2,7‐dimethyldiazapyrenium has a simpler mechanism.

The association of 1,3,6,8-pyrenetetrasulfonate (S4P) or 8-hydroxypyrene-1,3,6-trisulfonate (S3POH) with cationic surfactants possessing tetradecyl substituent was studied in aqueous solution at 298 K. Two types of nanoparticles were produced depending on the mixing ratio of the components. The self-assembly to negatively charged larger nanoparticles at low surfactant excess was always exothermic, whereas the formation and size diminution of the positive nanoparticles in the presence of larger amount of surfactants were practically thermoneutral. The alteration of the fluorescence spectrum upon self-organization of the constituents indicated π−π interaction between the pyrene moieties within the nanoparticles. In tetradecyltrimethylammonium bromide solution, S4P induced the formation of not only nanoparticles but also mixed micelles composed of supramolecular and conventional amphiphiles. A pH-responsive entropy-controlled transformation of nanoparticles to such mixed micelles was achieved when 1-methyl-3-tetradecyl-imidazolium cation had more than 19-fold molar excess over S3POH.

Quasi-reversible single electron transfer (ET) kinetics of methylviologen partly-included at the rim of 4-sulfonatocalix[n]arenes (n = 4,6 and 8) has been investigated in aqueous solution. ET rates were measured by Nicholson method with relatively large potential scan rates (0.9 V/s

The kinetics of entry into and exit from the cavity of cucurbit[7]uril (CB7) was studied by the stopped-flow method in water at various temperatures using pharmaceutically important natural isoquinoline alkaloids as guest compounds. The rate constant of the alkaloid-CB7 complex dissociation was separately determined exploiting the very strong competitive binding of the 1-adamantylammonium cation to CB7. The enthalpy and entropy of activation for the release of berberine from CB7 were significantly lower than those found in the case of the other alkaloids, suggesting different dissociation dynamics. CB7 initially moved from the energetically most stable position encompassing the isoquinoline moiety of berberine to the smaller benzodioxole part, which could leave the macrocycle with less structural distortion. Despite the same thermodynamic parameters of berberine and palmatine inclusion, the latter compound was encapsulated in and set free from CB7 much slower due to the more substantial steric hindrance. The most rapid entry into CB7 and the most exothermic binding were found for epiberberine and coptisine, the alkaloids substituted with the less spacious dioxole ring on their isoquinoline moiety.

Self-association of three biologically active natural quaternary benzo[c]phenanthridine alkaloids, nitidine, sanguinarine, and chelerythrine was studied by spectrophotometry, fluorescence spectroscopy, fluorescence decay measurements and isothermal titration calorimetry in aqueous solution. The increase of alkaloid concentration brought about moderate changes in the absorption spectra, while the fluorescence properties altered only in the case of nitidine. Enthalpy-controlled self-binding occurred and the variation of the association enthalpy was substantially compensated by the unfavorable entropic term. Nitidine dimerization was the most exothermic and the equilibrium constant of this process exceeded by a factor of ~5 the corresponding values of the other two alkaloids. The results of quantum chemical calculations agree well with the experimental data and provide information on the structural features of the dimers.

High binding constants of 19 inorganic cations with the cucurbit[n]uril homologues (CBn, n = 5, 6, 7, 8) in water were determined and the far-reaching consequences and interferences of the high affinities (millimolar to micromolar) are discussed.

Spontaneous formation of positively charged nanoparticles was observed upon mixing more than stoichiometric amount of chitosan with 4-sulfonatocalix[8]arene (SCX8) in acidic solution. The particle size did not change with SCX8 concentration, polymer chain length, and the degree of deacetylation at 0.002 ≤ SCX8/chitosan ≤0.043 molar ratios in 0.01 M HCl. However, larger aggregates were produced when chitosan concentration was increased. The most stable nanoparticles with 160 nm diameter and narrow size distribution were obtained at pH 4 using low molecular weight chitosan. These particles encapsulated coralyne with more than 90 % entrapment efficiency and 15 % loading capacity. A loading ratio of [coralyne]/[SCX8] = 1.7 was achieved without any stability loss. 4-Sulfonatocalix[4]arene induced the formation of slightly smaller nanoparticles than its homologs comprising 6 or 8 phenol units.

Absorption and fluorescence spectroscopic measurements, as well as isothermal calorimetric titrations showed that the biexponential decay kinetics of protonated ellipticine (EH + ) fluorescence in water originates from dimerization. Due to the high equilibrium constant for the association of two EH + and the intense fluorescence of the dimer, deviation from the exponential emission intensity decay commences below micromolar concentrations. Dimerization must be taken into account when EH + concentration is determined by spectrophotometry, and when EH + binding to substrates are studied. The molar absorption coefficients of the monomer and dimer were determined.

International audience; The effect of the chain length of the alkyl and alkoxy substituents on the binding characteristics of 1-alkyl-6-alkoxy-quinolinium cations was studied using 4-sulfonatocalix[4]arene (SCX4) and 4-sulfonatocalix[6]arene (SCX6) in neutral aqueous solutions at 298 K. Isothermal calorimetric titrations showed enthalpy-controlled inclusion with 1:1 stoichiometry. The equilibrium constants of complexation were always larger for the confinement in SCX4 than in its SCX6 homologue because the better matching between the host and guest sizes allowed more exothermic interaction. The binding affinity diminished with the lengthening of the aliphatic chain of the guests in the case of the association with SCX4, but insignificant change was found for SCX6 complexes. The most substantial change in the enthalpic and entropic contributions to the driving force of complex production occurred when the alkyl chain was linked to the heterocyclic nitrogen and the number of its carbon atoms varied between 1 and 4. 1 H NMR spectra evidenced that in SCX6, the 1-alkyl-6-alkoxy-quinolinium cations could be included within the macrocycle cavity. In the case of SCX4, the quinolinium ring is always inside the host, but the alkyl chain is included within SCX4 only for a short chain length (n up to 4). In contrast, the alkoxy chain displays a very weak interaction with the cavity irrespective of the length. Because of the outward orientation from the host, the lengthening of the alkoxy substituent of the quinolinium moiety barely influenced the thermodynamics of inclusion in SCX4. Distinct linear enthalpy−entropy correlations were found for the encapsulation in SCX4 and SCX6.

In order to reveal the influence of the guest molecular structure, the interactions between 4-sulfonatocalix[n]arene (SCXn) cavitands (n = 4 or 6) and two series of quinolinium derivatives were studied in neutral aqueous solutions at 298 K. For this, the long alkyl chain of the quinoliniums was attached either to the heterocyclic nitrogen (CmC1OQ+ m = 10, 12, or 14) or to the oxygen located in position 6 of the aromatic system (C1CmOQ+ m = 8, 10, or 12). All the quinolinium derivatives self-assembled with SCXn into nanoparticles (NP), whose size, zeta potential and composition were determined over a large molar mixing ratio range. Isothermal titration calorimetry showed that host-guest binding assisted the formation of negatively charged NPs in exothermic processes. The enthalpy gain in these associations significantly increased with the lengthening of the 1-alkyl group but was insensitive to the size of the SCXn macrocycle. The morphology of NPs was studied by cryo-TEM method. CmC1OQ+ organization with SCXn led to spherical NPs without regular inner structure. In contrast, C1CmOQ+-SCXn nanoaggregates usually had various shapes and the original morphologies exhibited lamellar domains with ~3 nm layer thickness. The different orientation of CmC1OQ+ and C1CmOQ+ in the cavitand was proposed to rationalize the morphological alterations.

The effect of temperature and NaCl concentration variations on the self-assembly of 1-methyl-3-tetradecylimidazolium (C14mim(+)) and 4-sulfonatocalix[6]arene (SCX6) was studied by dynamic light scattering and isothermal calorimetric methods at pH 7. Inclusion complex formation promoted the self-assembly to spherical nanoparticles (NP), which transformed to supramolecular micelles (SM) in the presence of NaCl. Highly reversible, temperature-responsive behavior was observed, and the conditions of the NP-SM transition could be tuned by the alteration of C14mim(+):SCX6 mixing ratio and NaCl concentration. The association to SM was always exothermic with enthalpy independent of the amount of NaCl. In contrast, NPs were produced in endothermic process at low temperature, and the enthalpy change became less favorable upon increase in NaCl concentration. The NP formation was accompanied by negative molar heat capacity change, which further diminished when NaCl concentration was raised.

The complexation of the highly fluorescent 6-methoxy-1-methyl-quinolinium (C1MQ) and the widely used herbicide, difenzoquat (DFQ), with 4-sulfonatocalix[4]arene (SCX4) macrocycle was studied by isothermal titration calorimetry, fluorescence and NMR spectroscopy in aqueous solutions at 298 K. Both guests produced 1:1 complexes with SCX4, but the binding affinity of C1MQ was more than one order of magnitude larger than that of DFQ in neutral medium. The higher stability of C1MQ-SCX4 complex originated from the significant enthalpy gain upon its formation. The encapsulation of C1MQ in SCX4 in the ground state resulted in an efficient fluorescence quenching due to electron transfer from the host to the excited guest. The marked difference in the fluorescence quantum yields for free and bound C1MQ was used to detect the competitive complexation of DFQ in SCX4.

The effect of headgroup variation on the association of supramolecular amphiphiles composed of 4-sulfonatocalix[6]arene (SCX6) and cationic surfactant possessing tetradecyl substituent was studied in aqueous solutions at pH 7. When the surfactant contained hydrophilic trimethylammonium, pyridinium, or 1-methylimidazolium headgroup, highly reversible temperature-responsive nanoparticle–supramolecular micelle transformation could be attained at appropriately chosen component mixing ratios and NaCl concentrations. In these cases, the substantial negative molar heat capacity change (ΔCp) rendered nanoparticle formation strongly endothermic at low temperature, whereas the assembly to supramolecular micelle was always accompanied by enthalpy gain. The ΔCp values became less negative when the charge density and the hydrophilic character of the surfactant headgroup diminished. The association of the more hydrophobic 6-methoxyquinolinium and quinolinium surfactants with SCX6 did not lead to supramolecular micelle ...

Slow wave activity (SWA) is a characteristic brain oscillation in sleep and quiet wakefulness. Although the cell types contributing to SWA genesis are not yet identified, the principal role of neurons in the emergence of this essential cognitive mechanism has not been questioned. To address the possibility of astrocytic involvement in SWA, we used a transgenic rat line expressing a calcium sensitive fluorescent protein in both astrocytes and interneurons and simultaneously imaged astrocytic and neuronal activity in vivo. Here we demonstrate, for the first time, that the astrocyte network display synchronized recurrent activity in vivo coupled to UP states measured by field recording and neuronal calcium imaging. Furthermore, we present evidence that extensive synchronization of the astrocytic network precedes the spatial build-up of neuronal synchronization. The earlier extensive recruitment of astrocytes in the synchronized activity is reinforced by the observation that neurons surrounded by active astrocytes are more likely to join SWA, suggesting causality. Further supporting this notion, we demonstrate that blockade of astrocytic gap junctional communication or inhibition of astrocytic Ca2+ transients reduces the ratio of both astrocytes and neurons involved in SWA. These in vivo findings conclusively suggest a causal role of the astrocytic syncytium in SWA generation.

The kinetics and thermodynamics of berberine inclusion in cucurbit[7]uril was studied by stopped-flow method, fluorescence titrations, and isothermal calorimetry in neat water. The ~500-fold fluorescence intensity enhancement upon encapsulation was exploited to monitor the complex formation in real time at various temperatures. The increase in the fluorescence intensity could be fitted well by assuming a simple 1:1 binding equilibrium without any intermediate formation. For the rate constants of association and dissociation, (1.9 ± 0.1) × 10(7) M(-1) s(-1) and (0.81 ± 0.08) s(-1) were found at 298 K, respectively. The ingression into the cavity of CB7 had 32 ± 2 kJ mol(-1) activation enthalpy, implying a constrictive binding, whereas 69 ± 2 kJ mol(-1) was obtained for the activation enthalpy of the egression. Substantial structural change had to occur when berberine passed through the tight carbonyl-rimmed portal of the macrocycle to reach the transition state. An enthalpy-driven complexation took place with a slight entropy gain.

A combination of absorption and fluorescence spectroscopic studies with isothermal calorimetric titrations and stopped-flow measurements is a powerful way to reveal the thermodynamics and kinetics of inclusion complex formation with cucurbit[8]uril (CB8). The unique photophysical characteristics of berberine (B(+)), a pharmaceutically important natural alkaloid, were exploited to distinguish the consecutive encapsulation processes, and to examine the confinement in the CB8 cavity. The highly environment sensitive fluorescence lifetime of B(+) permitted the selective detection of various cucurbituril complexes, and indicated to what extent the embedded guest was available for interaction with water. Highly stable 1 : 1 and 2 : 1 B(+) : CB8 complexes were produced due to the release of the high energy water molecules from the CB8 interior, and the second binding step proved to be almost 3 times more exothermic. The favorable entropy change contributed appreciably to the driving force of 1 : 1 encapsulation. In contrast, the embedment of the second B(+) in CB8 led to substantial entropy diminution. The kinetics of encapsulation was followed in real time by recording the fluorescence intensity change after rapid mixing of B(+) and CB8. No evidence was found for intermediates. The rate constants of (64 ± 9) × 10(6), and (5.0 ± 0.5) × 10(6) M(-1) s(-1) were found for the 1 : 1 and 2 : 1 associations, whereas 3.8 ± 0.6, and 0.6 ± 0.1 s(-1) were obtained as the rate constants of the reverse processes at 283 K, respectively.

The temperature dependence of the kinetics of flavopereirine inclusion in cucurbit[7]uril (CB7) was studied by a stopped-flow method in water. The substantial blue-shift of the emission band and the ∼4-fold fluorescence quantum yield enhancement upon host–guest binding permitted the monitoring of the formation and dissociation of the flavopereirine–CB7 1 : 1 complex in real time. The competitive binding of the 1-adamantylammonium cation with extremely high affinity was exploited to selectively and very accurately determine the kinetic parameters of the exit of flavopereirine from the CB7 cavity. The rate constants of the ingression into and the egression from CB7 were found to be 9.0 × 107 M−1 s−1 and 1.6 s−1 at 298 K, respectively. Both processes had substantial activation enthalpy implying that a steric barrier had to be overcome in the course of the reversible encapsulation. The 31 ± 2 kJ mol−1 activation enthalpy of the entry into CB7 was comparable to the 37 ± 2 kJ mol−1 enthalpy change upon the dissociation of the complex.

Fluorescence characteristics of a biologically active natural alkaloid, luotonin A (LuA), were studied by steady-state and time-resolved spectroscopic methods. The rate constant of the radiationless deactivation from the singlet-excited state diminished by more than one order of magnitude when the solvent polarity was changed from toluene to water. Dual emission was found in polyfluorinated alcohols of large hydrogen bond donating ability due to photoinitiated proton displacement along the hydrogen bond. In CH2Cl2, LuA produced both 1 : 1 and 1 : 2 hydrogen-bonded complexes with hexafluoro-2-propanol (HFIP) in the ground state. Photoexcitation of the 1 : 2 complex led to protonated LuA, whose fluorescence appeared at a long wavelength. LuA served as a bidentate ligand forming 1 : 1 complexes with metal ions in acetonitrile. The stability of the complexes diminished in the series of Cd(2+)Zn(2+)Ag(+), and upon competitive binding of water to the metal cations. The effect of chelate formation on the fluorescent properties was revealed.

The effect of 1:1 complex formation on the photochromic behavior of the merocyanine isomer of a nitro-substituted spirobenzopyran dye was studied in aqueous solution using 4-sulfonatocalixarene (SCXn) cavitands possessing four or eight phenol units. The binding constants were independent of the size of the macrocycle, and about 7-fold more stable associates were produced at pH 2.3 than in slightly alkaline solution. The complexation with SCXn diminished the acidity of protonated merocyanine (trans-MCH(+)) and precluded its photoinitiated transition to spirobenzopyran form, but did not affect the reactions in basic media. Upon exposure to light, the complexed trans-MCH(+) was converted to cis isomer. The association with 4-sulfonatocalix[4]arene slowed down the thermal back reaction in the dark to a larger extent than the confinement to 4-sulfonatocalix[8]arene. Both the activation energy and the Arrhenius A factor were significantly larger when the smaller, more rigid macrocycle served as a host.

The inclusion of 1-alkyl-3-methylimidazolium ions (C n mim + ) in 4-sulfonatocalix[8]arene was studied by isothermal titration calorimetry in aqueous solution at 298 K. Sequential formation of 1:1 and 2:1 complexes occurred in enthalpy driven reactions. The alteration of the molecular structure of the guest barely affected the driving force of the confinement of the first C n mim + . However, the binding affinity of the second C n mim + went through a maximum when the number of carbon atoms in the side chain was increased. The enthalpy and entropy change diminished linearly with the length of the aliphatic substituent of C n mim + for 1:1 complexation, but reached a minimum for the hexyl homologue in the case of 2:1 inclusion. Linear entropy–enthalpy correlations were found with smaller slope and intercept for the second binding step.

The effect of macrocycle size on the association of supramolecular amphiphiles composed of 4-sulfonatocalix[n]arene and 1-methyl-3-tetradecylimidazolium (C14mim+) was studied in aqueous solutions at pH 7. When the cavitand contained four sulfonatophenol units (SCX4), formation of spherical nanoparticles (NPs) was observed. By contrast, both supramolecular micelle (SM) and NP formation could be attained in the presence of NaCl when the larger, more flexible 4-sulfonatocalix[8]arene (SCX8) served as the host compound. The SCX8-promoted self-assembly into the SM was enthalpically more favorable than the NP production, but the molar heat capacity changes in the two processes barely differed. An addition of 50 mM NaCl significantly increased the enthalpy of C14mim+–SCX8 NP formation, thereby making the self-organization into the SM more favorable. The transformation of SM into NP at high temperatures was due to the substantial entropic contribution to the driving force behind the NP formation. The critical mic...

The encapsulation of protonated ellipticine (EH+) in the cavity of cucurbit[8]uril (CB8) was studied in water at pH 4 with spectrophotometric, fluorescence spectroscopic and isothermal calorimetric measurements. The formation of three types of inclusion complexes was observed depending on the host and guest concentrations. Not only one, but also two EH+ was capable of encapsulation in CB8 in 37 μM EH+ solution and the thermodynamics of the binding steps were revealed. The produced very stable complexes showed markedly different absorption and fluorescence properties. When large excess of CB8 was employed in dilute (0.49 μM) EH+ solution, sequential binding of two CB8 occurred to the monomer alkaloid bringing about a substantial alteration in the fluorescence decay kinetics. The driving force of the 1:2 guest:host complex formation was much lower than that of 1:1 encapsulation.

The effect of cucurbit[7]uril (CB7) on the spiropyran-merocyanine photochromic interconversion was studied in acidic and alkaline aqueous solutions. The merocyanine (MC) isomer was found to be the thermodynamically most stable form both in water and in the presence of CB7. A preferential binding of the protonated merocyanine (MCH(+)) to CB7 was observed with an equilibrium constant of 7.4×10(4) m(-1), and the complex formation led to significant diminution of acidity of the guest. The photoinduced transformation of MCH(+) to the spiropyran isomer was accelerated 2.3-fold upon addition of CB7, whereas the rates of the other photochromic processes were not affected. The partial inclusion of MCH(+) in CB7 led to dual fluorescence due to the incomplete deprotonation in the singlet-excited state.

The effect of inclusion complex formation on the photochromic behavior of a spirobenzopyran dye and its merocyanine isomer was studied in aqueous solution using cucurbit[8]uril (CB8) as a host. The merocyanine (MC) and protonated merocyanine (MCH(+)) were the most stable forms both in water and inside the cavity of CB8. The equilibrium constant of 1:1 complexation with CB8 was found to be 1.7 × 10(5) and 2.0 × 10(6) M(-1) for the former and latter species, respectively. The encapsulation led to significant change in the rate of the photoinduced and thermal photochromic transformations and hindered the hydrolysis of MC. The effect of CB8 on the reaction kinetics strongly altered with pH. The transition from the spiropyran form to trans-MC in a thermal reaction had 33 kJ mol(-1) lower activation energy and more than 5 orders of magnitude smaller Arrhenius pre-exponential factor in CB8 than in water.

The photooxidation of sanguinarine, coralyne and berberine was studied in oxygenated alkaline methanol solutions. Rose bengal as photosensitizer significantly accelerates the process, indicating the importance of singlet molecular oxygen in the reaction mechanism. The quantum yield of sensitized oxidation was found to increase significantly with pH and reaches 0.4 for berberine at pH 13.8. The direct oxidation of alkaloids is less efficient, the quantum yield does not exceed 0.01 even in oxygen-saturated solutions. The photoinduced electron ejection does not play a role in the oxidation. The uncharged pseudobase forms, which are present in alkaline medium, are oxidized much more easily than the alkaloid cations.

The binding of 1-alkyl-3-methylimidazolium ions (C n mim + ) to p -sulfonato-substituted calix[4]arene (SCX4) and calix[6]arene (SCX6) was studied by isothermal titration calorimetry in aqueous solution at 298 K. The complexation had 1:1 stoichiometry and was enthalpy driven for all cations. The equilibrium constants of inclusion were determined at pH 6.5 and compared to those previously reported at pH 2. The driving force of encapsulation showed smaller pH dependence for SCX4 than for SCX6. The binding enthalpy changed only slightly when the 1-alkyl moiety of the imidazolium ring was lengthened and did not depend on the size of the calixarene macrocycle. The complexation with SCX4 caused smaller entropy loss and steeper linear enthalpy–entropy correlation.

The encapsulation of biologically important compounds in the cavity of cucurbit[7]urils (CB7) brings about a variety of effects. The binding of lumichrome to CB7 promotes the tautomerization from alloxazine- to isoalloxazine-type structure in the ground-state, leading to substantial changes in the absorption and fluorescence properties. Even partial embedding in CB7 macrocycle is able to protect sanguinarine, a natural alkaloid, against nucleophilic addition and photooxidation. The inclusion of berberine in CB7 results in about 500-fold enhancement of its fluorescence intensity, and the change in its fluorescence decay characteristics indicates ternary complex formation with cations. DAPI (4′,6-diamidino-2-phenylindole dication) is an excellent fluorescent probe for the study of the CB7 complex formation with ionic liquids, surfactants, and biologically important compounds. The binding of 1-alkyl-3-methylimidazolium ions to CB7 is strongly exothermic; both the enthalpy and the entropy change in the reaction go through a minimum when the 1-alkyl group is lengthened, reaching the smallest values for the hexyl derivative.

The absorption and fluorescence characteristics of flavopereirine, a pharmaceutically important natural alkaloid, were studied to reveal how the complex formation and the change of the microenvironment affect the deactivation kinetics from the singlet-excited state. The fluorescence lifetime was not influenced by the ionic strength, but a significant deuterium effect was observed showing that hydrogen bonding in the singlet-excited state promoted energy dissipation. Nucleotides caused both static and dynamic quenching. The rate constant of the latter process increased when the nucleobase was capable of donating electron to the excited flavopereirine. The spectrophotometric measurements provided evidence for non-cooperative binding to double-stranded DNA with an equilibrium constant of 4.6 × 10(5) M(-1). Time-resolved fluorescence signals showed that three kinds of complexes are formed with distinct fluorescence lifetimes. Flavopereirine binding to chondroitin sulfate was also found, which led to different fluorescence characteristics at pH 2 and 6.

The photoprocesses of berberine, palmatine, coralyne, sanguinarine, flavopereirine and ellipticine were studied in several solvents. The quantum yields Φ(Δ) of singlet molecular oxygen formation of berberine, palmatine and sanguinarine are moderate in dichloromethane (0.2-0.6) and much smaller in acetonitrile or trifluoroethanol. For the other alkaloids examined, Φ(Δ) is rather independent of solvent polarity. The direct and ketone-sensitized photolysis, using steady-state irradiation at 313 nm or 248/308 nm laser pulses, was studied by absorption and fluorescence spectroscopy. Thereby, radicals were observed yielding eventually dihydro derivatives as major products, which are thermally back-converted on admission of oxygen. The quantum yield of conversion of alkaloids to dihydroalkaloids is enhanced in the presence of triethylamine. The reaction in the presence of ketones and electron or H-atom donors has a quantum yield of close to unity.

The inclusion of sanguinarine, a biologically active natural benzophenanthridine alkaloid, in cucurbit[7]uril (CB7) was studied by NMR and ground-state absorption spectroscopy, as well as steady-state and time-resolved fluorescence measurements in aqueous solution. The iminium form of sanguinarine (SA(+)) produces very stable 1 : 1 inclusion complex with CB7 (K = 1.0 × 10(6) M(-1)), whereas the equilibrium constant for the binding of the second CB7 is about 3 orders of magnitude smaller. Marked fluorescence quantum yield and fluorescence lifetime enhancements are found upon encapsulation of SA(+) due to the deceleration of the radiationless deactivation from the single-excited state, but the fluorescent properties of 1 : 1 and 1 : 2 complexes barely differ. The equilibrium between the iminium and alkanolamine forms is shifted 3.69 pK unit upon addition of CB7 as a consequence of the preferential encapsulation of the iminium form and the protection of the 6 position of sanguinarine against the nucleophilic attack by hydroxide anion. On the basis of thermodynamic cycle, about 225 M(-1) is estimated for the equilibrium constant of the complexation between the alkanolamine form of sanguinarine (SAOH) and CB7. The confinement in the CB7 macrocycle can be used to impede the nucleophilic addition of OH(-) to SA(+) and to hinder the photooxidation of SAOH.

The thermodynamics of 1:1 inclusion complex formation between 1-alkyl-3-methylimidazolium type ionic liquids and cucurbit[7]uril was studied by isothermal titration calorimetry in aqueous solution at 298 K. The encapsulation proved to be enthalpy driven for all cations used. The enthalpy change upon binding (ΔH) became more negative when the 1-alkyl moiety of the imidazolium ring was gradually lengthened reaching the most exothermic association with the hexyl derivative. Further increase of the number of carbon atoms in the aliphatic chain led to less negative ΔH values. The much smaller entropy change followed the trend of ΔH. The slope of the linear enthalpy–entropy correlation found in the present work is significantly smaller than that reported previously for cyclodextrin complexes, because the more rigid CB7 macrocycle cannot undergo significant conformational change upon complexation.

The properties of triplet-excited trans-4-hydroxy-4′-nitrostilbene were studied by photochemical means. This species produces singlet molecular oxygen with a quantum yield of ΦΔ = 0.4 in benzene and 0.05 in acetonitrile. Population of the triplet state was also detected by flash photolysis. The triplet yield is substantial in benzene or toluene and small in polar solvents. The major photoprocess is trans → cis isomerization, whose quantum yield is Φt-c = 0.45 in benzene and smaller in more polar media. The effects of solvent polarity on the triplet reactivity were revealed. For trans-4-hydroxy-2′,4′-dinitrostilbene, ΦΔ and Φt-c are much smaller. The photoreaction to the corresponding hydroxyphenylisatogen was examined and mechanistic aspects were discussed.

The excited singlet state properties of 4′-nitro- and 2′,4′-dinitro-substituted trans-4-hydroxystilbenes were studied in various solvents. The fluorescence quantum yield (Φf) of the former compound in solvents unable to form strong hydrogen bonds goes through a maximum as a function of the solvent polarity parameter E T N , reaching the highest value of 0.31 in butyronitrile. In contrast, a monotonous diminution of Φf and moderate changes were found in hydrogen bonding media. The addition of nitrogen-heterocyclic compounds leads to both dynamic and static fluorescence quenching due to excited-state proton transfer along the hydrogen bond. trans-2′,4′-Dinitro-4-hydroxystilbene emits only weak fluorescence in all solvents studied.

Addition of cucurbit[7]uril to an aqueous solution of lumichrome led to the formation of a new red-shifted band in both the absorption and fluorescence spectra indicating that binding to this rigid macrocyclic host facilitated the partial transformation into isoalloxazine-type structure. Global analysis of the results of spectrophotometric and spectrofluorometric titrations provided log K = 3.92 ± 0.06 for the logarithm of the equilibrium constant of 1:1 association. The dual fluorescence of the complex was quenched by protons in a diffusion-controlled process. Cucurbit[7]uril was found to exert negligible effect on the deprotonation of lumichrome in basic solution.

A clinically important natural isoquinoline alkaloid, berberine, was used as a fluorescent probe to study the encapsulation of 1-alkyl-3-methylimidazolium (CnMIm+) type ionic liquids in 4-sulfonato-substituted calix[4]arene (SCX4) and calix[6]arene (SCX6) at pH 2. Addition of ionic liquids to the aqueous solution of berberine−SCXn inclusion complexes brought about considerable fluorescence intensity diminution due to the extrusion of berberine from the macrocycle into the aqueous phase by the competitive inclusion of CnMIm+ cation. The lengthening of the aliphatic side chain of the imidazolium moiety diminished the equilibrium constant of complexation with SCX4, but enhanced the stability of SCX6 complexes. Larger binding strength was found for SCX4.