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Cyclodextrins and cucurbiturils are very good receptors of hydrophobic species in water. The product stability (logK > 10 for complexes involving neutral guests and cucurbiturils were reported) is a consequence of strongly exothermic association, rationalized by non-classical hydrophobic effect (release of energetically rich cavity water). However, our recent study of the adamantyl-based guest inclusion within β-cyclodextrin (β-CD) revealed an almost complete compensation of ΔrH°(T) and –TΔrS°(T) contributions to logK temperature dependence. The results could be explained by the Frank-Evans model of adamantane hydration at lower (classical hydrophobic effect) and gradual “iceberg melting” at higher temperatures. We have therefore decided to study the complexation of both (poly)cyclic and linear aliphatic compounds with cucurbit[7]uril (CB7) and β-CD in a wide temperature range, both experimentally (ITC, ROESY NMR spectroscopy) and computationally (classical, solvent-explicit MD simulations). The investigated guests were chosen with the aim of supressing all thermodynamic contributions to hosting apart those associated with the hydrophobic effect. The study provided missing pieces to a jigsaw puzzle explaining the thermodynamic contributions to standard complexation Gibbs energies, as well as insights into hydration of guest and host cavities. Apart from that, intriguing differences concerning the enthalpic and entropic effect of CB7 and β-CD cavity dehydration were revealed.

Calixarenes are macrocyclic compounds comprised of phenolic units ortho-linked by methylene bridges. Depending on their size and substituents at upper or lower rim, these ligands have been found to be suitable receptors for various ionic and/or neutral species. Calixarenes bearing suitable binding sites as well as fluorescent moieties (e. g. naphthalene, anthracene, pyrene, phenanthridine) have been recognized as highly sensitive ion sensors, which can be attributed to the prominent sensitivity of fluorescence spectroscopy. In this work the binding affinities of fluorescent calix[4]arene derivatives L1 and L2 towards transition metal cations in acetonitrile were investigated by means of UV, fluorescence, and NMR spectroscopies, as well as isothermal titration calorimetry. The obtained results were discussed regarding the hosts and guests structural properties.

The temperature and solvent effect on the complexation of various guests (Figure 1) with α-, β- and γ-cyclodextrin and cucurbit[7]uril was explored experimentally and by means of molecular dynamics simulations. The stability constants of all investigated complexes were by far the highest with cucurbit[7]uril in water. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in almost complete enthalpy-entropy compensation was observed for most explored host-guest systems. For those systems complexation thermodynamics was in line with the classical rationale of the hydrophobic effect at lower temperatures, and the non-classical explanation at higher ones. The optimized inclusion complex structures corresponded to those deduced by means of NMR spectroscopy and the experimentally obtained and calculated ΔrG° were in very good agreement.

Calixarenes are a class of supramolecular hosts that can be easily functionalized to give receptors for various chemical species.Due to the prominent sensitivity of fluorescence spectroscopy and high affinity of these macrocyclic ligands towards cations, it is possible to prepare highly sensitive ion sensors by introducing fluorescent substituents into the calixarene moiety. In the scope of this work, the binding affinities of calix[4]arene derivative L towards alkaline earth metal cations in several organic solvents were investigated by means of isothermal titration calorimetry, UV and fluorescence spectroscopies, as well as molecular dynamics simulations. The obtained results provided a detailed insight into the complexation thermodynamics and structures of the ligand and complexes formed.

Calixarenes are macrocyclic oligomers consisted of four or more phenolic residues linked by methylene groups in ortho position. Depending on their size and substituents at lower and/or upper rim, these compounds have been found to be very efficient receptors for various chemical species. Those bearing suitable binding sites as well as fluorescent moieties can be considered as very sensitive ion sensors due to the high sensitivity of fluorescence spectroscopy. In the scope of this work, two fluorescent phenanthridinebased calix[4]arene derivatives L1 and L2 (Figure 1) were designed and prepared. Their binding affinities towards alkali, alkaline earth, and transition metal cations in various organic solvents (acetonitrile, methanol, ethanol, N, N- dimethylformamide, dimethyl sulfoxide) were investigated by means of UV, fluorimetry, NMR, and isothermal titration calorimetry. The obtained results were discussed regarding the structural characteristics of the studied calixarene derivatives and solvation abilities of the solvents used.

The medium effects on the complexation of alkali-metal cations with calix[4]arene derivatives containing triazole subunits (compunds L and l) was systematically explored by means of microcalorimetric and UV-Vis spectrophotometric titrations in dimethylformamide, methanol water and acetonitrile. First two solvents were chosen for the purpose of comparison of receptors binding abilities as both ligands exhibit sufficient solubility required for complexation investigations in these media. The cation hosting in MeCN was studied to compare the ligand L with other tertiary amide calixarene derivatives. On the basis of ligand dissolution enthalpies, and the literature data, the enthalpies of reactants and the product transfer among solvents were obtained. The studied compounds binded alkali-metal cation rather efficiently and similarly in methanol and in dimethylformamide, whereas the acetonitrile was the most favourable reaction medium for alkalimetal cation reactions with receptor L. Compound l proved to be a remarkable host for Na+ in water. The cation binding was enthalpically controlled. The complexation of Li+ with ligand L in acetonitrile was the only entropically favourable reaction. The peak-affinity of both compounds for Na+ was noticed for all studied reactions. The 1H NMR investigations revealed relatively low affinity of the calixarene sodium complex for the inclusion of solvent molecule in the calixarene hydrophobic cavity, with the exception of acetonitrile. In many examined cases, the considerable solvent effect on the complexation equilibria was proven to be an interesting interplay between the transfer enthalpies and entropies of the reactants and the products.

Calixarene tertiary amide derivatives are well known to have very high affinities towards alkali and alkaline earth metal cations, and can be glycosylated to produce potentially water-soluble compounds. Those additionally bearing fluorescent moieties can be considered as very sensitive fluorimetric ion sensors due to the prominent sensitivity of fluorescence spectroscopy. In the scope of this work the binding affinity of fluorescent, phenanthridine-based calix[4]arene glycoconjugate towards alkali and alkaline earth metal cations was investigated by means of spectrophotometry, fluorimetry, microcalorimetry, and 1H NMR spectroscopy. The thermodynamic parameters of the corresponding complexation reactions (i.e. stability constants of the complexes formed, standard reaction Gibbs energies, enthalpies, and entropies) were determined and discussed regarding the charge density and solvation of the cations as well as structural properties of the ligand.

The temperature and solvent effect on the complexation of various guests with α-, β- and γ-cyclodextrin and cucurbit[7]uril was explored experimentally and by means of molecular dynamics simulations. The stability constants of all investigated complexes were by far the highest with cucurbit[7]uril in water. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in almost complete enthalpy- entropy compensation was observed solely in water. The complexation thermodynamics was in line with classical rationale of the hydrophobic effect at lower temperatures, and the non-classical explanation at higher ones. Unlike in water, the hosting in formamide and ethylene glycol could be attributed to non- classical solvophobic effect. The optimized inclusion complex structures corresponded to those deduced by means of NMR spectroscopy and the experimentally obtained and calculated ΔrG° were in very good agreement. The carried out research bridged the gap between the classical and non-classical rationale of hydrophobic effect and demonstrated that solvophobically driven formation of inclusion complexes is not a water-limited phenomenon. However, among explored structured solvents, water stood out as unique solvation and complexation medium.

Calixarenes are a class of supramolecular hosts that can be easily functionalized with suitable donor groups at the lower and/or upper rim to give efficient receptors for various chemical species. Those bearing fluorescent moieties can be considered as potentially very sensitive fluorimetric ion sensors due to the prominent sensitivity of fluorescence spectroscopy and high affinity of these macrocyclic ligands towards cations. In the scope of this work, the binding affinities of calix[4]arene derivatives L1 and L2 towards alkali metal cations in acetonitrile, methanol and ethanol were investigated by means of UV spectrophotometry, fluorimetry and isothermal titration calorimetry. The thermodynamic parameters of the corresponding reactions were determined and discussed. The results obtained by molecular dynamics simulations and DFT calculations, together with those of NMR experiments, provided an additional insight into the structures and complexation properties of the ligands and the complexes formed.

Calixarenes are macrocyclic oligomers consisted of four or more phenolic residues linked by methylene bridges in the ortho position. As such, they can be easily functionalized with ketone, ester, amide, or other functional groups on the lower and/or upper rim to give efficient receptors for various ionic or neutral species. Due to the prominent sensitivity of fluorescence spectroscopy and high affinity of these macrocyclic ligands towards cations, it is possible to prepare highly sensitive ion sensors by introducing fluorescent substituents into the calixarene moiety. In the scope of this work, the binding affinities of tertiary amide and ester phenantridinebased calix[4]arene derivatives L1 and L2 towards alkali, alkaline earth and lanthanide cations in various organic solvents (acetonitrile, methanol, ethanol, N, N‐dimethylformamide, dimethyl sulfoxide) were investigated. Stability constants of the corresponding complexes were determined (or in some cases only assessed) by means of UV spectrophotometry, fluorimetry, and isothermal titration calorimetry. The latter technique also provided information on reaction enthalpies and entropies. The obtained thermodynamic parameters were discussed regarding the structural characteristics of the studied compounds and solvation properties of the solvents used.

Kaliksareni su makrociklički oligomeri koji se sastoje od četiri ili više fenolnih podjedinica povezanih metilenskim skupinama u ortho- položaju fenola. Specifičan oblik i mogućnost njihove funkcionalizacije čine kaliksarene zanimljivim molekulama domaćinima za razne neutralne i nabijene goste. Da bi se povećao afinitet za vezanje kationa, najčešće se na donji obod kaliksarena uvode ketonske, esterske ili amidne skupine. Funkcionalizacijom kaliksarena fluorescentnim supstituentima moguće je prirediti visokoosjetljive senzore za niz kemijskih vrsta, pri čemu ti supstituenti, osim što su zaslužni za fluorescenciju spoja, mogu sudjelovati i u vezanju kationa. U ovom radu proučavana su kompleksacijska svojstva derivata kaliks[4]arena koji, osim tercijarnih amidnih supstituenata, kao dio veznog mjesta posjeduje i fenantridinske fluorofore čija su potencijalna kation-vezujuća svojstva temeljena na prisustvu aromatskih dušikovih atoma. Mikrokalorimetrijskim, spektrofotometrijskim i fluorimetrijskim titracijama istražene su odgovarajuće reakcije kompleksiranja s kationima zemnoalkalijskih metala u više otapala (acetonitril, metanol, etanol). Odabir otapala zasnovan je na topljivosti liganda, solvatacijskim svojstvima i mogućnosti povezivanja vodikovim vezama. Određene su konstante stabilnosti kompleksa te standardne entalpije i entropije reakcija kompleksiranja. Također, istražen je utjecaj otapala i vezanja kationa na intenzitet fluorescencije navedenog kaliksarena te njegova potencijalna primjena kao fluorescentnog kationskog senzora. Da bi se stekao dojam o mogućim strukturama istraživanog spoja i njegovih kompleksa te utjecaj inkluzije molekula otapala u hidrofobnu kaliksarensku šupljinu, provedene su odgovarajuće simulacije molekulske dinamike.

Calixarenes are a class of supramolecular hosts that can be easily functionalized with suitable donor groups at the lower and/or upper rim to give efficient receptors for various ionic or neutral species. Due to the prominent sensitivity of fluorescence spectroscopy and high affinity of these macrocyclic ligands towards cations it is possible to prepare highly sensitive ion sensors by introducing fluorescent substituents into the calixarene moiety. In the scope of this work, the binding affinities of tertiary amide and ester phenantridine-based calix[4]arene derivatives L1 and L2 towards alkali metal cations in various organic solvents (acetonitrile, methanol, ethanol, N, N-dimethylformamide and dimethyl sulfoxide) were investigated experimentally (UV spectrophotometry, fluorimetry and isothermal titration calorimetry) as well as by means of classical molecular dynamics simulations which provided an additional insight into the complexation properties and structures of the complex species formed. The results gained by the latter technique indicated the occurrence of inclusion of solvent molecules in the calixarene hydrophobic cavity of the free and complexed ligands, which was found to significantly affect the complexation equilibria. The obtained thermodynamic reaction parameters were discussed regarding the structural characteristics of the studied compounds and solvation properties of the solvents used.

The solvent influence on the complexation of amphiphilic mannosides containing different non-polar moities with β-cyclodextrin and cucurbit[7]uril was explored in a wide range of temperatures by means of microcalorimetry and NMR spectroscopy. The stabilities of the complexes formed were higher in water than in other hydrogen-bonded solvents (ethylene glycol, formamide, N-methylformamide, and methanol), whereby all reactions were enthalpically controlled. The explored guest preffered cucurbit[7]uril as host. In the case of complexation reactions involving β- cyclodextrin and investigated guests in water notable temperature dependence of ΔrH° and ΔrS° was noticed. This resulted in almost perfect enthalpy-entropy compensation. The standard thermodynamic parameters for mannoside bindng with β-cyclodextrin in organic solvents exhibited relatively weak temperature dependence. The complex stability was strongly influenced by the compatibilty of guest and host cavity sizes, as well as the flexibility and the structure of the mannoside hydrophobic group. The carried out investigations clearly demonstrate that solvophobically driven formation of cyclodextrin and cucurbit[7]uril inclusion complexes is not a water limited phenomenon.

Combination of a lipophilic adamantyl subunit and a highly polar guanidine moiety affords adamantylaminoguanidines, compounds with membrane compatible features capable of binding to complementary molecules possessing phosphate groups.[1] We recently showed that adamantylaminoguanidines can effectively be incorporated into liposomes and the resulting liposomeformulations were capable of recognizing complementary liposomes.[2] We therefore turned outattention to preparing multicomponent self-assembled supramolecular nanovesicles capable of recognition and binding to fluorescently labelled DNA.[3] Our findings suggest that such nanovesicles(Figure 1) could potentially be applied as nonviral gene delivery vectors.

Cyclodextrines (CDs) have been extensively studied due to their ability to host wide variety of hydrophobic compounds in water thus increasing their solubility in this solvent, and hence bioavailability.[1] The focus of our studies so far has been the synthesis of adamantyl glycosides and the evaluation of thermodynamic parameters of their complexation with b-CD in water.[2] Our present investigations have been directed to the complexation of other amphiphilic glycosides, namely, n-butyl, t-butyl, n-hexyl, cyclohexyl, n-octyl and cyclooctyl 2-(a- D-mannopyranosyloxy)acetates with b-CD in water and in organic solvents. Therefore, we present the synthesis of novel amphiphilic mannosylated esters of acetic acid possessing various alkyl parts (linear, branched or cyclic, Fig. 1). The esters were prepared by the reaction of acetylated or benzylated mannopyranose and corresponding esters of bromoacetic acid. Their complexation with b-CD was studied by means of titration calorimetry and NMR spectroscopy (1H, HSQC, COSY and ROESY techniques). The thermodynamic parameters of complexation (reaction enthalpies, standard reaction entropies, binding constants) were determined. Obtained results provide a deeper insight in correlations between guest structure and its complexation thermodynamics in investigated solvents.

The solvent influence on the complexation of amphiphilic mannosides, consisting of different non-polar moities, with β-cyclodextrin was explored in a range of temperatures (5 ≤ ϑ/ ºC ≤ 65) by means of microcalorimetry and NMR spectroscopy. The complexation was observed only in strongly hydrogen-bonded solvents (water, formamide, N-methylformamide, and ethylene glycol). The stabilities of complexes were higher in water than in investigated organic solvents, whereby all reactions were enthalpically controlled. A notable temperature dependence of ΔrH○ and ΔrS○ was noticed in water. In contrast, the standard complexation parameters in other investigated solvents exhibited relatively weak temperature dependence. As expected, the complex stability was strongly influenced by compatibilty of the guest and the β-cyclodextrin cavity sizes, as well as the flexibility and structure of the hydrophobic group of investigated mannosides. The carried out investigations provided a deeper insight into the hosting process, demonstrating that solvophobically driven formation of cyclodextrin inclusion complexes is not a water limited phenomenon.

Uvođenjem šećernih podjedinica na donji obod kaliks[4]arena s efikasnim veznim mjestom za alkalijske katione pripravljen je kaliksarenski derivat L topljiv u vodi. Kalorimetrijskim i spektrofotometrijskim titracijama istražene su odgovarajuće reakcije kompleksiranja u tom otapalu, kao i metanolu i formamidu. Određene su konstante stabilnosti kompleksa te standardne entalpije i entropije reakcija kompleksiranja. Kompleksacijska svojsta spoja L uspoređena su s onima analognog glikokonjugata koji sadrži osam glukoznih podjedinica.[1] Receptor L vrlo dobro veže alkalijske katione u svim ispitanim otapalima, a najveći afinitet pokazuje prema Na+. Reakcije alkalijskih kationa s istraženim makrociklom entalpijski su kontrolirane, a standardne reakcijske entropije negativne su u svim slučajevima, osim za kompleksiranja Li+ u metanolu. Opaženi utjecaj broja glukoznih podjedinica na stabilnost kompleksa posljedica je zanimljivog odnosa reakcijskih entalpija i entropija, posebice u vodi i metanolu.

U predavanju će biti opisano sveobuhvatno istraživanje koordinacijskih reakcija nekoliko karbonilnih derivata kaliks[4]arena s alkalijskim kationima u većem broju otapala. Termodinamičke veličine kompleksiranja (konstante stabilnosti kompleksa, standardne reakcijske Gibbsove energije, entalpije i entropije), dobivene primjenom različitih eksperimentalnih metoda, bit će diskutirane s obzirom na strukturu reaktanata i produkata reakcija, a poseban će naglasak biti stavljen na utjecaj otapala reaktanata i produkata, te intra- i intermolekulskih vodikovih veza na ravnoteže proučavanih reakcija. U tu će svrhu biti prezentirani i pojašnjeni termodinamički ciklusi transfera gosta, domaćina i kompleksa između otapala. Rezultati spomenutih istraživanja jasno ukazuju na izniman utjecaj solvatacije na kompleksacijska svojstva kaliksarena, odnosno koordinacijski reakcija općenito. Pored navedenog, pružaju detaljniji uvid u povezanost strukture makrocikličkih spojeva i njihove kemijske reaktivnosti. Kako će biti pokazano, takve informacije mogu poslužiti kao osnova za ciljani dizajn novih, učinkovitih receptora za ione i neutralne kemijske vrste.

Kaliksareni su makrociklički oligomeri koji se sastoje od četiri ili više fenolnih podjedinica povezanih metilenskim skupinama u ortho-položaju fenola. Specifičan oblik i mogućnost njihove funkcionalizacije čine kaliksarene zanimljivim molekulama domaćinima za razne neutralne i nabijene goste. Kako bi se povećao afinitet za vezanje kationa, na donji i/ili gornji obod kaliksarena najčešće se uvode ketonske, esterske ili amidne funkcionalne skupine. Uvođenjem fluorescentnih supstituenata u strukturu kaliksarena moguće je prirediti visokoosjetljive senzore za niz kemijskih vrsta, pri čemu ti supstituenti, osim što su zaslužni za fluorescenciju spoja (fluorofori), mogu sudjelovati i u vezanju kationa (ionofori). U ovom radu proučavana su kompleksacijska svojstva derivata kaliks[4]arena koji, osim amidnih supstituenata, kao dio veznog mjesta posjeduje i fenantridinske fluorofore koji također mogu sudjelovati u vezanju kationa. Mikrokalorimetrijskim, spektrofotometrijskim i fluorimetrijskim titracijama istražene su odgovarajuće reakcije kompleksiranja s kationima alkalijskih metala u više otapala (acetonitril, metanol, etanol, N, N-dimetilformamid, dimetilsulfoksid). Određene su konstante stabilnosti kompleksa te standardne entalpije i entropije reakcija kompleksiranja. Također, istražen je utjecaj otapala i vezanja kationa na relativni intenzitet fluorescencije navedenog kaliks[4]arena te njegova potencijalna primjena kao fluorescentnog kationskog senzora.

The p-tert-butyl calix[4]arenes with carbonyl- containing substituents at the lower rim are known to be effective receptors for alkali- metal cations. Apart from the chemical nature of the attached functionalities, and the cation size, the complexation thermodynamics is strongly influenced by the reactant and the product solvation.[1, 2] In the first part of the work the thermodynamic parameters of alkali-metal cation complexation with a simple calix[4]arene ketone derivative (L) in methanol, ethanol, N-methylformamide, N, N- dimethylformamide, dimethyl sulfoxide, and acetonitrile were determined.[1] The compound L was found to be rather efficient receptor for alkali-metal cations. The cation binding was enthalpically controlled with the peak affinity for Na+. To examine the possible inclusion of the investigated solvent molecules into the hydrophobic basket of the receptor and its sodium complex detailed spectro-photometric, calorimetric and 1H NMR titrations in chloroform were carried out. The solvent binding was much more favorable in the case of NaL+ when compared to free ligand. The sodium complex exhibited the highest affinity for the acetonitrile, which can, at least in part, explain the highest stability of the complexes in this solvent. In the second part of the work, the inclusion of acetonitrile molecule in the hydrophobic cavity of a more rigid tertiary amide calix[4]arene derivative and the corresponding sodium complex was investigated. The obtained data provided an insight into the influence of the calixarene flexibility on the thermodynamics of adduct formation.

Kaliksareni su makrociklički oligomeri koji se sastoje od četiri ili više fenolnih podjedinica povezanih metilenskim skupinama u ortho-položaju fenola. Specifični oblik i mogućnost njihove funkcionalizacije čine kaliksarene vrlo zanimljivim molekulama domaćinima za razne neutralne i nabijene goste. Kaliksareni koji posjeduju ketonske, esterske ili amidne funkcionalne skupine na donjem obodu pokazuju veliki afinitet za vezanje kationa. Uvođenjem fluorescentnih supstituenata u strukturu kaliksarena moguće je prirediti visokoosjetljive senzore za niz kemijskih vrsta.Pripravljen je derivat kaliks[4] arena koji ima kombinaciju klasičnih amidnih supstituenata kao dio veznog mjesta dok su na preostalim podjedinicama vezani fenantridinski fluorofori koji također sudjeluju u procesu kompleksiranja. Kalorimetrijskim, spektrofotometrijskim i fluorimetrijskim titracijama istražene su odgovarajuće reakcije kompleksiranja s kationima alkalijskih metala u acetonitrilu i metanolu. Određene su konstante stabilnosti kompleksa te standardne entalpije i entropije reakcija kompleksiranja. Fluorimetrijskim titracijama istražen i utjecaj otapala i vezanja kationa na relativni intezitet fluorescencije, a time i potencijalna primjena kaliksarenskog receptora kao fluorescentnog senzora za katione alkalijskih metala.

Calixarenes are macrocyclic oligomers consisted of four or more phenolic residues linked by methylene groups in the ortho position and can be easily functionalized to give receptors for vast number of ionic or neutral species. Calixarenes bearing fluorescent moieties can be considered as potentially very sensitive fluorimetric ion sensors due to the high sensitivity of fluorescence spectroscopy and high affinity of these macrocyclic ligands towards cations. In the scope of this work, two novel fluorescent phenathridine-based calix[4]arene derivatives were designed and prepared. The binding affinities of these compounds towards metal cations in several solvents (acetonitrile, methanol, ethanol, N, N-dimethylformamide, dimethylsufoxide) were investigated. Phenanthridine moities were introduced at a lower calix[4]arene rim and served both as fluorescent probes and parts of cation-binding site. Stability constants of the corresponding complexes were determined by means of UV spectrophotometry, fluorimetry and isothermal microcalorimetry. The latter technique also provided information on reaction enthalpies and entropies. The obtained results were discussed regarding the structural characteristics of the calixarene derivatives and differences in solvation abilities of the solvents used.

Calixarenes are macrocyclic oligomers consisted of four or more phenolic residues linked by methylene bridges in the ortho position and can be easily functionalized to give receptors for various ionic or neutral species. Calixarenes bearing fluorescent moieties can be considered as potentially very sensitive fluorimetric ion sensors due to the high sensitivity of fluorescence spectroscopy and high affinity of these macrocyclic ligands towards cations. [1-3] In the scope of this work, novel fluorescent phenathridine-based calix[4]arene derivatives L1 and L2 were designed and prepared (Figure 1) and their complexation properties towards metal cations in several solvents were investigated. Phenanthridine moities were introduced at a lower calixarene rim and served both as fluorescent probes and parts of cation-binding site. Stability constants of the corresponding complexes were determined by means of fluorimetry, UV spectrophotometry, NMR spectroscopy and isothermal titration calorimetry.

Kaliksareni su makrociklički oligomeri koji se sastoje od fenolnih podjedinica povezanih metilenskim skupinama u ortho-položaju fenola. Specifični oblik i mogućnost njihove funkcionalizacije čine ovu klasu spojeva vrlo zanimljivim molekulama domaćinima za razne neutralne i nabijene goste. Kaliksareni koji posjeduju ketonske, esterske ili amidne funkcionalne skupine na donjem i/ili gornjem obodu pokazuju veliki afinitet za vezanje kationa. Uvođenjem fluorescentnih supstituenata u strukturu kaliksarena moguće je prirediti visokoosjetljive senzore za niz kemijskih vrsta. Pripravljeni su derivati kaliks[4]arena L1 i L2 koji uz klasična amidna i esterska vezna mjesta imaju fluoroforne fenatridinske podjedinice na donjem kaliksarenskom obodu. Kalorimetrijskim, spektrofotometrijskim i fluorimetrijskim titracijama istražene su odgovarajuće reakcije kompleksiranja s kationima metala u više otapala. Određene su konstante stabilnosti kompleksa te standardne entalpije i entropije reakcija kompleksiranja. Fluorimetrijskim titracijama istražen i utjecaj otapala i vezanja kationa na relativni intezitet fluorescencije, a time i potencijalna primjena kaliksarenskog receptora kao fluorescentnog senzora za katione metala.

Kaliksareni su makrociklički oligomerni spojevi sastavljeni od četiriju ili više fenolnih podjedinica povezanih metilenskim skupinama u ortho-položaju fenola. Raznolikost kaliksarenskih derivata posljedica je varijabilnog broja fenolnih podjedinica makrocikala te mogućnosti funkcionalizacije na gornjem i donjem kaliksarenskom obodu. Cilj ovoga rada bio je istražiti utjecaj otapala na kompleksiranje kationa alkalijskih metala (M+) ketonskim derivatom kaliks[4]arena (L). Mikrokalorimetrijskim i spektrofotometrijskim titracijama određene su konstante stabilnosti kompleksa ML+ u navedenim otapalima te je potvrđena entalpijska kontrola procesa kompleksiranja.1 Kompleksiranje Na+ s L uočeno je u svim ispitivanim otapalima, dok je kompleksiranje ostalih alkalijskih kationa opaženo samo u metanolu i acetonitrilu. Spektrofotometrijskim, mikrokalorimetrijskim i 1H-NMR titracijama ispitana je inkluzija molekula otapala u hidrofobnu šupljinu kompleksa NaL+ kao potencijalni dodatni pokretač nastanka kompleksa ML+. Uočen je slabi afinitet kaliksarenske hidrofobne šupljine prema metanolu i N-metilformamidu te nešto jači afinitet za vezanje acetonitrila. Primjena izotermne mikrokalorimetrije u istraživanju formiranja kompleksâ ML+, istraživanje temperaturne ovisnosti topljivosti liganda L u ispitivanim otapalima i poznavanje standardnih termodinamičkih funkcija tranfera kationa alkalijskih metala omogućili su konstruiranje termodinamičkih ciklusa iz kojih slijedi detaljna termodinamička interpretacija različitih utjecaja ispitivanih otapala na stabilnost kompleksa ML+. Različiti solvatacijski utjecaji na formiranje kompleksa mogu se za većinu promatranih otapala objasniti uzimajući u obzir samo solvataciju kationa i kompleksa, dok u slučaju acetonitrila važnu ulogu ima i inkluzija molekule otapala u kaliksarensku hidrofobnu šupljinu.

Cyclodextrines (CDs) have been studied due to their ability to host wide variety of hydrophobic compounds in water and increase their solubility in water, hence bioavailability [1]. Recently, we reported the synthesis of adamantyl glycosides and the thermodynamic parameters of their complexation with β-CD in water [2] Our present investigations have been directed to the complexation of amphiphilic glycosides, namely, adamant-1- yl, cyclohexyl and benzyl 2-(α-D- mannopyranosyloxy)acetates with β-CD in water and in organic solvent. In this work we present the synthesis of novel amphiphilic mannosylated derivatives of acetic acid with different alkyl parts (Figure 1). The esters were prepared by the reaction of acetylated mannopyranose and corresponding esters of bromoacetic acid with linear, branched or cyclic alkyl parts. Their complexation with β- CD was studied by means of titration calorimetry and NMR spectroscopy. Solvents used in calorimetric experiments were strongly hydrogen bonded (water, alcohols) in which the inclusion of similar guests in β-CD is still largely unexplored. The thermodynamic parameters of complexation (reaction enthalpies, standard reaction entropies, binding constants) were determined. Obtained results provide a deeper insight in correlations between guest structure and its complexation thermodynamics in examined solvents.

Calixarenes are macrocyclic oligomers consisted of four or more phenolic residues linked by methylene bridges in the ortho position. By their relatively easy functionalization, a vast number of efficient receptors for various ionic and neutral species have been prepared [1]. Calixarenes bearing fluorescent moieties could be considered as potential sensitive fluorimetric ion sensors due to the high sensitivity of fluorimetry [2, 3]. In the scope of this work novel fluorescent antracene- and diphenylantracene-based calix[4]arene derivatives 1 and 2 were designed and synthesized. Their complexation with alkali- metal cations was investigated as well. Antracene and diphenylantracene moieties were introduced at a lower calixarene rim and served as fluorescent groups positioned close to the cation-binding site. Due to the low solubilities of the prepared calix[4]arene derivatives in solvents of moderate permittivities, their complexation was studied in methanol–dichloromethane and acetonitrile– dichloromethane solvent mixtures (φ = 0.5). Stability constants of the corresponding complexes were determined (in some cases only assessed) by means of fluorimetry, UV spectrophotometry, and isothermal microcalorimetry. The latter technique also provided information on reaction enthalpies and entropies. The obtained thermodynamic quantities were discussed regarding the structural characteristics of the ligands and solvation properties of the solvents used.

Adamant-1-yl, cyclohexyl and benzyl 2-(α-D-mannopyranosyloxy)acetate were prepared and their complexation with β-cyclodextrin in water, formamide and ethylene glycol was explored microcalorimetricaly and by means of NMR spectroscopy in a wide of range of temperatures (5 ≤ θ / °C ≤ 65). Formation of inclusion complexes with all explored derivatives was observed in water. The corresponding stability constants were the highest for adamantly based compound, somewhat lower for the cyclohexy mannoside and much lower for the benzyl derivative. The binding of adamantly mannoside in organic solvents occurred at all temperatures explored, whereas the complexation of cyclohexyl derivative could be noticed only at 5 °C. The inclusion of the benzene subunit into the macrocycle cavity in formamide and in ethylene glycol was not observed. The stabilities of the adamantly and cyclohexyl complexes were higher in water than in formamide and ethylene glycol. All reactions were enthalpically controlled at all temperatures examined. The less favourable complexation in formamide and ethylene glycol with respect to water is mainly due to low ΔrSº values in these solvents. In addition, ΔrHº and ΔrSº for complexation of cyclohexyl and adamantyl mannosides in water decreased significantly with temperature, whereas no such effect could be observed in organic solvents. The main driving force for complex formation can be attributed to solvofobic solvation of host cavity and that of the guest. Despite this fact, the solvation of hydrophobic subunit of the guest and the macrocycle cavity seems to be notably different in water when compared to explored organic solvents.

Adamant-1-yl, cyclohexyl and benzyl 2-(α-D- mannopyranosyloxy)acetate were prepared and their complexation with β-cyclodextrin in water, formamide and ethylene glycol was explored microcalorimetricaly and by means of NMR spectroscopy in a wide of range of temperatures (5 ≤ θ / °C ≤ 65). Formation of inclusion complexes with all explored derivatives was observed in water. The corresponding stability constants were the highest for adamantly based compound, somewhat lower for the cyclohexy mannoside and much lower for the benzyl derivative. The binding of adamantly mannoside in organic solvents occurred at all temperatures explored, whereas the complexation of cyclohexyl derivative could be noticed only at 5 °C. The inclusion of the benzene subunit into the macrocycle cavity in formamide and in ethylene glycol was not observed. The stabilities of the adamantly and cyclohexyl complexes were higher in water than in formamide and ethylene glycol. All reactions were enthalpically controlled at all temperatures examined. The less favourable complexation in formamide and ethylene glycol with respect to water is mainly due to low ΔrSº values in these solvents. In addition, ΔrHº and ΔrSº for complexation of cyclohexyl and adamantyl mannosides in water decreased significantly with temperature, whereas no such effect could be observed in organic solvents. The main driving force for complex formation can be attributed to solvofobic solvation of host cavity and that of the guest. Despite this fact, the solvation of hydrophobic subunit of the guest and the macrocycle cavity seems to be notably different in water when compared to explored organic solvents.

(S)-N-(adamant-1-yl)-3-(β-D- mannopyranosyloxy)-2-methylpropanamide, was prepared by condensation of 1- adamantamine and mannose through short linker. The complexation thermodynamics of this compound with β-cyclodextrin and 6-O- monotosyl-β-cyclodextrin in water, methanol, ethylene glycol, formamide, and N-methylformamide was explored by means of microcalorimetry and NMR spectroscopy. The complex formation was observed in water, ethylene glycol and formamide. The temperature dependence (5 ≤ θ / ºC ≤ 65) of standard thermodynamic complexation parameters in these solvents was studied in detail. The structures of reaction products were investigated by means of NMR spectroscopy. The stabilities of the complexes were highest in water followed by formamide and ethylene glycol, whereby all reactions were enthalpically controlled at temperatures examined. The ΔrHº values for complexation reactions in formamide and ethylene glycol were rather similar in the studied temperature range, whereas the corresponding values in water decreased with the increase in temperature. The reaction entropies in all examined solvents were less favourable at higher than at lower temperatures. The stability constant of the synthetic macrocycle and adamantyl mannoside complex was lower than that with β-cyclodextrin. The main driving force for the formation of complexes can be attributed to solvophobic solvation of the host cavity and the adamantane subunit. The differences in the temperature dependence of the complex stabilities in water and both formamide and ethylene glycol can be explained by more pronounced changes of water structure with change in temperature.

U okviru rada sintetizirana su tri lipofilna O-manozida (adamant-1-ilni, cikloheksilni i benzilni 2-(α-D- manopiranoziloksi)acetat). O-Manozidi pripravljeni su reakcijom acetilirane manopiranoze i estera bromoctene kiseline. Zaštitne skupine s manoze uklonjene su Zemplenovom deacetilacijom. Reakcije pripravljenih spojeva s β-ciklodekstrinom istražene su u vodi, formamidu i etilen- glikolu titracijskom mikrokalorimetrijom i spektroskopijom NMR. Kompleksiranje svih spojeva u vodi ispitano je u širem temperaturnom intervalu (5 ≤ θ / °C ≤ 65). Stvaranje inkluzijskih kompleksa u vodi zamijećeno je u slučaju sva tri derivata manoze, a kompleksiranje cikloheksanskog derivata u formamidu i etilen-glikolu moglo se zamijetiti samo pri 5 °C. Inkluzijski kompleksi s adamantanskim derivatom stabilniji su od onih s cikloheksilnim derivatom, dok je stabilnosti kompleksnih vrsta s benzilnim derivatom u vodi vrlo niska. Konstante stabilnosti kompleksa adamantanskog i cikloheksanskog derivata u vodi veće su od onih u formamidu i etilen-glikolu, pri čemu su sve istražene reakcije entalpijski kontrolirane. Vrijednosti ΔrH i ΔrS za kompleksiranje adamantanskog i cikloheksanskog derivata s β- ciklodekstrinom u vodi smanjuju se s porastom temperature. Razlike u afinitetu ciklodekstrina za cikličke alkilne podjedinice u istraženim otapalima posljedica su znatno nižih vrijednosti ΔrS u etilen-glikolu i formamidu u odnosu na vodu. Kompleksiranje lipofilnih derivata s ciklodekstrinom u istraživanim otapalima većim je dijelom uzrokovano solvofobnom solvatacijom gosta i hidrofobne unutrašnjosti ciklodekstrina.