Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• Synthesis and structure of cyclodextrin-based (poly)rotaxanes CDs are cyclic sugar molecules in which multiple glucose units that are connected by α-1,4 bonds, e.g., α-CD, β-CD, and γ-CD (glucose-unit numbers 6, 7, and 8, respectively), are used for scientific studies and industrial productions (Figure 2

• substituted benzene ring, and γ-CD can host further bigger guest molecules, such as pyrene or two aliphatic chains, in one cavity. The ability of CD to form an inclusion complex structure is drastically affected by the cavity size or the modification strategy for the hydroxy groups on CD. To evaluate the

• synthesize the rotaxane. For example, Anderson and co-workers reported the synthesis of γ-CD–based [2]rotaxane via the Suzuki reaction using a dicarboxylic acid end-capping reagent; they reported a 17% yield (Scheme 1C) [39]. To perform an end-capping reaction in water, multiple hydrophilic substituents

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• properties of γ-CD (the largest of the three most abundant native CDs), the main experimental methods applied in this study were differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). By coupling these techniques with density functional theory (DFT) calculations we try to shed some

• light on the mechanism of the γ-CD hydration and to address some unanswered questions: (i) what are the preferable locations for water molecules in the macrocyclic cavity (“hot spots”); (ii) what are the major factors contributing to the stability of the water cluster in the CD interior; (iii) what type

• of interactions (i.e., water–water and/or water–CD walls) contribute to the stability of the water assemble; (iv) how does the mechanism of the γ-CD hydration compare with those of its α-CD and β-CD counterparts. Keywords: cyclodextrin; DFT calculation; DSC/TG; hydration; thermodynamic

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• solubility [14][15]. As early examples of the latter approach in the 1990s, Wennerström and co-workers reported the study of supramolecular BiCAP complexation of C60 with γ-cyclodextrin (γ-CD) [16]. Shinkai and co-workers synthesized water-soluble calixarene derivatives to form water-soluble complexes with

Spatial arrangements of cyclodextrin host–guest complexes in solution studied by ¹³C NMR and molecular modelling

• Konstantin Lebedinskiy,
• Ivan Barvík,
• Zdeněk Tošner,
• Ivana Císařová,
• Jindřich Jindřich and
• Radim Hrdina

Beilstein J. Org. Chem. 2024, 20, 331–335, doi:10.3762/bjoc.20.33

• was detected for carbons 1 and 3 (in red color). The same 1D 13C NMR spectra were measured for guest molecule 1 in host cavities of β-CD and γ-CD, showing almost no split of prochiral carbon peaks and suggesting a higher degree of conformational flexibility of the host–guest complexes than for the

• ). Having established the method, we chose various cyclic compounds (noradamantane, adamantane, cyclohexane derivatives) with desired symmetry and measured NMR spectra of these guest molecules (2–8) in α-cyclodextrin and cyclodextrins with a larger cavity (β-CD and γ-CD, Figure 4). In all cases, the 1H NMR

• . The 3D densities show the spatial distribution of prochiral atoms within MD simulations. Studied host–guest complexes and splitting of guests’ prochiral carbons in their 13C NMR spectra. Molecular modelling of the host–guest complexes of compound 4 with α-CD, β-CD and γ-CD. X-ray analysis of the α-CD

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• exposed to the native CDs (α-CD, β-CD, γ-CD) and four β-CD derivatives: the randomly methylated-β-CD (RAMEB), the low methylated-β-CD (CRYSMEB), the hydroxypropyl-β-CD (HP-β-CD) and the sulfobutyl ether-β-CD (SBE-β-CD) at different CD/DPPC molar ratios (1:1, 10:1, and 100:1). The membrane permeability was

• membranes; this effect increased with CDs concentration. Among the studied CDs, α-CD, β-CD, and RAMEB were the most permeabilizing CDs on the different membranes. Similar modifications of SRB release from the various liposomal formulations were obtained with HP-β-CD, CRYSMEB, and SBE-β-CD. γ-CD was the less

• internal cavity and a hydrophilic outer surface [1]. The common CDs are the native α-CD, β-CD, and γ-CD consisting of 6, 7, and 8 ᴅ-glucopyranose units, respectively. Due to their limited water solubility (especially β-CD), native CDs can be chemically or enzymatically modified (by e.g., alkylation

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• low reactivity of these phthalimides, 10 mol % of catalyst was required. Cross-coupling reaction of sulfoximines 44 with N‑(arylthio)succinimides 1 catalyzed by a nanomaterial containing hexagonal boron nitride (h-BN) and γ-cyclodextrin-supported copper(II) acetate (h-BN@γ-CD@Cu(OAc)2) was developed

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• represented in the pharmaceutical market, in at least 130 marketed products [2]. Examples of the use of CDs in medicines are β-CD in cetirizine tablets and cisapride suppositories, γ-CD in a minoxidil solution, HP-β-CD in itraconazole antifungal, in intravenous and oral solutions, sulfobutyl ether β-CD in

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• Cyclodextrins (CDs) are studied for more than one hundred years due to their unique properties related to their spatial macrocyclic structure that comprises six to eight α-ᴅ-glucopyranose (Glcp) units for the natural α-, β-, and γ-CD [1][2][3]. All hydroxy groups are oriented to the exterior of the macrocycle

• the co-precipitation from a saturated solution. The peony oil content in the complex was almost 26%, with a high ratio of unsaturated FA glycerides of ≈90% [20]. In a very recent study, perilla (Perilla frutescens (L.) Britton) seed oil was complexed by γ-CD and the inclusion complex was used for

• unsaturated fatty acid glycerides significantly decreases the stability of hazelnut oil. Only one study was performed on the γ-CD nanoencapsulation of hazelnut oil by a co-precipitation method and the thermal decomposition of the complex was evaluated by TG [34]. One way of enhancing the oxidative stability

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• easier process than the optimization of a new monosubstitution reaction on a native CD [5]. Monotosylation of the primary rim of CDs is the most widely used method to obtain C-6 monofunctionalized CDs. Tosyl chloride (TsCl) reacts with α-, β-, and γ-CD in pyridine to give the C-6-monosubstituted product

• monosulfonated compound is separated by recrystallization from hot water in the case of the β-CD derivative, and by chromatography in the case of α- and γ-CDs. The larger cavity size of γ-CD is the reason of polysubstitution when TsCl is used [9]. To ensure a better yield of the monosubstituted product, bulkier

• sulfonyl chloride reagents are used. 2-Naphthalenesulfonyl chloride in pyridine is one common method. However, the concentration of γ-CD must be lower than 20 mM to favor monosubstitution and to ensure the optimal yield (around 30%) after recrystallization from hot water [9]. Sometimes purification using

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• ingredients (APIs) is necessary to render them bioavailable. This study addresses the poor solubility of two potent steroid hormones, 17β-estradiol (BES) and progesterone (PRO), via their complexation with two water-soluble native cyclodextrins (CDs) namely β-CD and γ-CD. The hydrated inclusion complexes β

• was of interest to us to establish to what extent the native host compounds β-CD and γ-CD could improve the aqueous solubilities of BES and PRO, specifically upon dissolution of their solid hydrated inclusion complexes whose accurately derived ternary formulae were established in this study. The

• relatively low cost of these CDs and in particular the low toxicity of γ-CD are advantageous for potential drug delivery. Furthermore, the amorphous nature of highly water-soluble CD derivatives (e.g., hydroxypropyl-CD and sulfobutyl ether CD) precludes their formation of crystalline inclusion complexes

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• tetracene in the saturated solution is shown in Figure 5. This chart implies an actual increase in solubility of tetracene for the majority of the tested samples. Since the size and shape of the cavities of α-CD and γ-CD are not comparable with tetracene's geometry, they do not provide any changes from the

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• molecules and protect those agents from environmental degradation [1][2]. Cyclodextrins (CDs) serve as one of the simplest encapsulating systems. CDs are cyclic oligosaccharides composed of 1→4 linked α-ᴅ-glucopyranose units (6, 7, and 8 for the most common α-, β-, and γ-CD). CDs are well known for their

• easiest accessibility; besides, β-CD forms usually the strongest inclusion complexes compared to α-CD and γ-CD. The amino-β-CD was prepared according to published procedures [25][26][27]. Common commercially available volatile aldehydes 2a–j (Figure 2) were chosen as the aldehyde reactants. Some of the

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• guest and a less efficient asymmetric induction. In contrast, α-7a and γ-CD 9a produced (E)-6 with a poor ee (<3 and 5%, respectively) because of the size mismatch between (Z)-6 and this host cavity. These results suggested that the ee value of the supramolecular photochirogenesis system depend on

• , Yagi, et al. reported that the visible-light-driven hydrogen evolution of the supramolecular system could be achieved by the host–guest complexation between the cobaloxime CoPyS and γ-CD (Figure 10) [30]. Upon visible-light irradiation, the CoPyS:γ-CD 1:1 complex exhibited an enhanced photocatalytic H2

• negatively charged CoPyS and EY was suppressed by the inclusion of γ-CD. Calixarene-based photocatalysis CAs are derived from the shape of the chalice. They can be obtained by bridging phenolic units through methylene groups in the meta-position. Their rigid goblet structure has two edges. The wider upper

Particle size effect in the mechanically assisted synthesis of β-cyclodextrin mesitylene sulfonate

• Stéphane Menuel,
• Sébastien Saitzek,
• Eric Monflier and
• Frédéric Hapiot

Beilstein J. Org. Chem. 2020, 16, 2598–2606, doi:10.3762/bjoc.16.211

• purification steps. We especially focused our attention on the utilization of cyclodextrins (CDs), which are cyclic α-ᴅ-glucopyranoside-based saccharides. CDs feature the advantage of adjustable cavity sizes and a broad synthetic diversity. The most commonly used CDs are α-CD, β-CD, and γ-CD, that consist of 6

Mechanochemical green synthesis of hyper-crosslinked cyclodextrin polymers

• Alberto Rubin Pedrazzo,
• Fabrizio Caldera,
• Marco Zanetti,
• Silvia Lucia Appleton,
• Nilesh Kumar Dhakar and
• Francesco Trotta

Beilstein J. Org. Chem. 2020, 16, 1554–1563, doi:10.3762/bjoc.16.127

• extraction) functionalized material, with a less negative ζ potential. Experimental Materials β-Cyclodextrin (β-CD), α-cyclodextrin (α-CD), and γ-cyclodextrin (γ-CD) were kindly provided by Roquette Italia SpA and Wacker Chemie. Carbonyldiimidazole (CDI, ≥97.0% (T)), 1,4-diazabicyclo[2.2.2]octane (DABCO

• ) synthesis. Conditions: nitrogen flow, ramp rate 10 °C/min, rt to 700 °C. Thermogravimetric analysis of α, β and γ-CD-based carbonate nanosponges, obtained through ball-mill synthesis. Conditions: nitrogen flow, ramp rate 10 °C/min. Adsorption of organic dyes by ball-mill synthesized β-CD-based carbonate

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• Jason Yin Hei Man Ho Yu Au-Yeung Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China 10.3762/bjoc.15.177 Abstract A series of hetero [4]-, [5]- and [6]rotaxanes containing both cucurbit[6]uril (CB[6]) and γ-cyclodextrin (γ-CD) as the macrocyclic components

• have been synthesized via a threading-followed-by-stoppering approach. Due to the orthogonal binding of CB[6] to ammonium and γ-CD to biphenylene/tetra(ethylene glycol), the [n]rotaxanes display a specific sequence of the interlocked macrocycles. In addition, despite of the asymmetry of γ-CD with

• -CD), seven (β-CD) and eight (γ-CD) glucose units are important molecular hosts that show binding to a wide range of compounds and find applications in different fields including food and pharmaceutical industries [1][2][3][4][5]. CDs are of cone shape with two different openings: a narrower primary

Reaction of oxiranes with cyclodextrins under high-energy ball-milling conditions

• László Jicsinszky,
• Federica Calsolaro,
• Katia Martina,
• Fabio Bucciol,
• Maela Manzoli and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2019, 15, 1448–1459, doi:10.3762/bjoc.15.145

• more effective synthesis of highly substituted γ-CD. Epichlorohydrin-crosslinked CD-polymers (CDPs) have also been effectively prepared in the ball mill. The unoptimised preparations of soluble and insoluble CDPs displayed very small particle size distributions, while the prepared polymers currently

• , which signified its incomplete conversion. This effect was found in both β- and γ-CD reactions after 2 hours. The complete conversion of the reagent was found upon increasing the milling time to 4 hours. Finally, 3.5 h milling was found to completely convert the propylene oxide in cases with low DS

• values. The reaction mixtures were always in a fine powder state over the entire course of the reactions, including salt formation. When using CD-hydrates, their natural state and as they are available from the suppliers, a hard CD-salt solid stuck to the jar wall in both β- and γ-CD, unlike with dried

Fabrication of supramolecular cyclodextrin–fullerene nonwovens by electrospinning

• Hiroaki Yoshida,
• Ken Kikuta and
• Toshiyuki Kida

Beilstein J. Org. Chem. 2019, 15, 89–95, doi:10.3762/bjoc.15.10

• introducing functional groups into the molecule directly. Among them, the formation of a 2:1 inclusion complex of γ-CD and C60 has been evaluated in various solvents such as water [21], toluene/water [22], DMSO [23], and DMF/water [24]. Although an impressive report that a 2:1 complex in water can be utilized

• as a homogeneous catalyst for nitrogen reduction under ambient conditions was published, the concentration of the complex in water is very low [25]. Thus, the development of γ-CD–C60 nonwovens by electrospinning might be useful as a novel inhomogeneous solid catalyst containing more C60. In this

• parameters similar to the case without the guest because the guest molecule is isolated from the solvent molecules by two γ-CD molecules. This is in contrast with the part of the guest molecule uncovered by γ-CD which may interact with the solvent molecules in the case of a 1:1 inclusion complex. Moreover

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• , has been investigated. It has been shown that administration of HP-β-CD has significantly reduced lysosomal cholesterol accumulation albeit the need for high doses is likely to be detrimental and might cause cell death [9][10][11]. Sulfobutyl ether-β-CD and sulfobutyl ether-γ-CD showed efficacy with

Synthesis and supramolecular properties of regioisomers of mononaphthylallyl derivatives of γ-cyclodextrin

• Markéta Bláhová,
• Sergey K. Filippov,
• Lubomír Kováčik,
• Jiří Horský,
• Simona Hybelbauerová,
• Zdenka Syrová,
• Tomáš Křížek and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2017, 13, 2509–2520, doi:10.3762/bjoc.13.248

• , Hlavova 8, 128 43, Prague 2, Czech Republic Department of Analytical Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43, Prague 2, Czech Republic 10.3762/bjoc.13.248 Abstract Monosubstituted derivatives of γ-cyclodextrin (γ-CD) are suitable building blocks for supramolecular polymers

• , and can also serve as precursors for the synthesis of other regioselectively monosubstituted γ-CD derivatives. We prepared a set of monosubstituted 2I-O-, 3I-O-, and 6I-O-(3-(naphthalen-2-yl)prop-2-en-1-yl) derivatives of γ-CD using two different methods. A key step of the first synthetic procedure is

• a cross-metathesis between previously described regioisomers of mono-O-allyl derivatives of γ-CD and 2-vinylnaphthalene which gives yields of about 16–25% (2–5% starting from γ-CD). To increase the overall yields, we have developed another method, based on a direct alkylation of γ-CD with 3

Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

• Magdalena Ceborska,
• Magdalena Zimnicka,
• Aneta Aniela Kowalska,
• Kajetan Dąbrowa and
• Barbara Repeć

Beilstein J. Org. Chem. 2017, 13, 2252–2263, doi:10.3762/bjoc.13.222

• complex with α-CD and pseudorotaxane inclusion-type complexes with β-, and γ-CDs. UV–vis titrations at pH 7.4 gave association constants for the obtained complexes. The stability of the complexes increases in the series: α-CD/PTX < γ-CD/PTX << β-CD/PTX. The association of PTX with a monomer cyclodextrin

• studied. Native CDs are water-soluble cyclic oligosaccharides, products of starch degradation, which contain six (α-CD), seven (β-CD) or eight glucopyranose units (γ-CD), accordingly, linked by α-1,4-glycosidic bonds (Figure 1b). They are toroid-like shaped and possess a cone-like hydrophobic cavity of

• (FA) with β-CD and γ-CD are far more stable than exclusion associate of FA and α-CD [16]. From collisional experiments we have also learnt that augmented stability of both inclusion complexes is mainly due to the increase of electrostatic forces and hydrogen bonds between FA and β- or γ-CD in the gas

Superstructures with cyclodextrins: Chemistry and applications IV

• Gerhard Wenz

Beilstein J. Org. Chem. 2017, 13, 2157–2159, doi:10.3762/bjoc.13.215

• , buckminsterfullerene C60 was covalently linked to two γ-CD rings [14]. This conjugate is highly soluble in water because it forms a sandwich-like self-complex, which makes it particularly useful as a sensitizer for singlet oxygen 1O2 generation [14]. Amphiphilic CD derivatives with oligoethylene oxide side chains form

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• , neuroprotecting, and suppression or prevention of tumors. The present work describes the preparation of a water-soluble, solid inclusion compound of fisetin with gamma-cyclodextrin (γ-CD), a cyclic oligosaccharide approved for human consumption. A detailed physicochemical analysis of the product is carried out

• GRAS status (list of food additives that are ‘generally recognized as safe’) [9]. The present work describes the preparation of a water-soluble, solid inclusion compound of fisetin with γ-CD (see Scheme 1 for structure and atom labeling). The formation of the γ-CD·fisetin inclusion compound as a solid

• product improves its stability and makes it easier to handle, transport and store. Furthermore, the used encapsulation method applied only edible ingredients: γ-CD, water, and ethanol, being thus suitable for future applications in food fortification. A detailed physicochemical analysis of the product

The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• susceptibility to degradation limit its application. The aim of our study was to improve the solubility and photostability of Ner through its encapsulation in different cyclodextrins (CDs). The formation constants of cis-, trans-Ner and their commercial mixture with various CDs (α-CD, β-CD, γ-CD, HP-β-CD, RAMEB

• Ner with seven CDs: α-CD, β-CD, γ-CD, HP-β-CD, RAMEB, CRYSMEB and SBE-β-CD using phase solubility studies coupled to HPLC. The Kf values were determined for the separate isomers and their commercial mixture. To confirm the Kf values obtained for the isomeric mixture, UV-visible spectroscopy was

• low aqueous solubility of Ner, phase-solubility studies were conducted to examine the ability of different CDs (α-CD, β-CD, γ-CD, HP-β-CD, RAMEB, CRYSMEB and SBE-β-CD) to solubilize Ner. All concentrations were determined for each isomer from their commercial mixture by HPLC. The mean intrinsic

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• spectroscopy. Liquid chromatography and tandem MS fragmentation studies [21][22][23] are also important additions in deeper structural characterization of CD-oligoester conjugates. The L-LA was reacted with α-, β- and γ-CD (Scheme 1) in bulk at 110 °C in order to ensure a good dispersion of reactants. The

• -, β- and γ-CD-LA products are shown in Supporting Information File 1, Figure S1. The nature of the separated compounds was partially confirmed by "off line" MALDI–MS measurements of the eluted fractions. Full MALDI–MS identification of all collected LC fractions for α-, β- and γ-CD-LA and LC ELSD

• –MALDI–MS allowed estimating the maximum number of monomer units per CD molecule for each of the α-, β- and γ-CD systems. It may be observed that the highest number of L-LA monomer units were grafted on β-CD (27 dilactate units) while for α-CD and γ-CD were obtained maximum values of 18 and 19 dilactate