Susana S. Braga

Solid state inclusion compound of S-ibuprofen in β-cyclodextrin: structure and characterisationElectronic supplementary information (ESI) available: crystal and data collection parameters and relevant O⋯O contacts (divided in six different groups) for βCD∶S-Ibu. See: http://www.rsc.org/suppdata/nj/b2/b207272f/

A crystalline inclusion complex was isolated from the reaction of β-cyclodextrin (βCD) with aqueous S-(+)-ibuprofen (S-Ibu). The existence of a true inclusion complex in the solid state was confirmed by a combination of powder X-ray diffraction (XRD), single crystal X-ray diffraction, thermogravimetric analysis (TGA), FTIR and 13C CP MAS NMR spectroscopies. The inclusion compound crystallises in the non-centrosymmetric monoclinic space group C2 with a 2∶1 host∶guest stoichiometry. The crystal structure consists of a head-to-head dimer of βCD molecules stacked along the crystallographic c axis, thus forming a slightly tilted channel-type structure.

Experimental and theoretical study of the interaction of molybdenocene dichloride (Cp2MoCl2) with β-cyclodextrin

A crystalline 1:1 inclusion complex was isolated from the reaction of β-cyclodextrin (β-CD) with aqueous Cp2MoCl2. The existence of a true inclusion complex in the solid-state was confirmed by a combination of powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), FTIR and Raman spectroscopy, and magic-angle spinning (MAS) 13C NMR spectroscopy. Ab initio calculations were carried out to generate the possible inclusion geometries and calculate the vibrational frequencies for Cp2MoCl2 in the 100–400 cm−1 region. The best organometallic–β-CD interaction geometry was found to be one with one Cp ligand inside the host cavity. The vibrational spectra support the existence of this structure and in addition confirm that the organometallic is included with the MoCl bond intact.

Chloramphenicol·cyclodextrin inclusion compounds: co-dissolution and mechanochemical preparations and antibacterial action

β-Cyclodextrin (βCD) inclusion compounds of chloramphenicol in the solid-state were prepared via two different procedures, co-crystallisation from aqueous solution and the solvent-free method of co-grinding. Chloramphenicol inclusion into permethylated βCD (TRIMEB) was also performed by co-dissolution in ethanol. The co-crystallisation procedure was the best for preparing chloramphenicol·βCD in 1:1 stoichiometry in high purity, while with the co-grinding treatment and the same starting proportion, a complete inclusion was not achieved. Microcrystals of chloramphenicol·βCD inclusion compound presented polymorphism, crystallising simultaneously in the triclinic P1 or monoclinic C2 space groups. Only crystals of the latter were suitable for single-crystal diffraction and data for the guest atoms was comprised of a smeared-out electron cloud, so theoretical calculations were used to propose their plausible geometry and location inside the host molecules. The co-grinding procedure curbed polymorphism and allowed the preparation of chloramphenicol·βCD in the amorphous state; chloramphenicol·TRIMEB prepared by co-dissolution of the components in a 1:1 proportion was also an amorphous material. The influence of inclusion with βCD and TRIMEB on the antimicrobial performance of chloramphenicol was evaluated, and both inclusion compounds demonstrated selective action against Enterococcus faecalis strains ATCC 29212 and A33562 and Listeria monocytogenes ATCC 7644. Chloramphenicol·TRIMEB also had higher activity against the E. faecalis strains A35906, 9308 and E4856 and against Listeria inocua.

Synthesis of ferrocenyldiimine metal carbonyl complexes and an investigation of the Mo adduct encapsulated in cyclodextrin

Cr and Mo tetracarbonyl complexes bearing the diimine ligand N,N′-bis(ferrocenylmethylene)ethylenediamine (FcNN) have been prepared from the ligand and M(CO)6. Two isomeric forms of (FcNN)Mo(CO)4, corresponding to the cis,cis and cis,trans geometries with respect to the CN bonds of the free ligand, were shown to exist in a 1∶12.5 ratio by 1H NMR (NOE experiments). By contrast, only the trans,trans isomer is observed for the Cr complex (FcNN)Cr(CO)4. The compounds (FcNN)M(CO)4 show ferrocene-based irreversible oxidation processes that lead to the deposition of a film at the electrode surface. (FcNN)Mo(CO)4 was immobilised in permethylated β-CD (TRIMEB) by addition of the guest to a solution of TRIMEB in dichloromethane. Removal of the solvent led to the isolation of an inclusion compound with a 2∶1 host∶guest stoichiometry, as evidenced by powder X-ray diffraction, thermogravimetric analysis, FTIR and 13C CP MAS NMR spectroscopy. The electrochemical properties of (FcNN)Mo(CO)4 upon encapsulation are discussed.

Encapsulation of Cyano(cyclopentadienyl) Complexes of Iron with β-cyclodextrin

Inclusion compounds have been prepared comprising g -cyclodextrin (CD) molecules as the host and half-sandwich cyano complexes of iron as the guests. High yields of crystalline one-to-one adducts were obtained by treatment of CpFe(CO) 2 CN and K[CpFe(CO)(CN) 2 ] with g -CD. In the case of CpFe(dppe)CN [dppe=bis(diphenylphosphine)ethane], a non-stoichiometric product is obtained and it is evident that the organometallic guests are easily liberated from the host cavities. The products were characterized in the solid-state by elemental analysis, powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), FTIR and CP MAS NMR ( 13 C, 31 P) spectroscopy. Additional information concerning the possible structure of the inclusion compounds was obtained from ab initio calculations using a two-layer approximation. The best organometallic- g -CD interaction is obtained with deep inclusion of the cyclopentadienyl ring, a geometry that is not possible in the case of the CpFe(dppe)CN system due to the size and orientation of the dppe ligand.

Structure of the β-Cyclodextrin·p-Hydroxybenzaldehyde Inclusion Complex in Aqueous Solution and in the Crystalline State

Abstractβ-Cyclodextrin (β-CD) and p-hydroxybenzaldehyde (p-HB) were studied by 1H-NMR in deuterated aqueous solution and the stoichiometry of the resulting complex (1:1) was determined by the continuous variation method. Inclusion of p-HB in β-CD was confirmed by the observation of NMR shifts for the inside H5 protons of the β-CD cavity. In the solid state X-ray analysis was carried out and revealed the detailed structure of the inclusion complex. Two β-CDs cocrystallize with four p-HB and 9.45 water molecules[2(C6H10O5)7·4C7H6O2·9.45H2O] in the triclinic space group P1 with unit cell parameters: a = 15.262(2), b = 15.728(1), c = 16.350(1) Å, α = 92.67(1)°, β = 96.97(1)°, γ = 103.31(1)°. The anisotropic refinement of 1973 atomic parameters converged at an R-factor = 0.066 for 10157 data with Fo2 > 2σ (Fo2). The 2:4 stoichiometry for the β-CD inclusion complex with p-HB in the crystalline state is different from that obtained in solution. β-CD forms dimers stabilized by direct O2(m)1O3(m)1·O2(n)2O3(n)2 hydrogen bonds (intradimer) and by indirect O6(m)1·O6(n)2 hydrogen bonds with one or two bridging water molecules joined in between (interdimer). These dimers are stacked like coins in a roll constructing infinite channels where the p-HB molecules are included. The p-HB molecules direct their polar CHO and OH groups into the nonpolar β-CD cavities and are hydrogen bonded to each other, yielding infinite, antiparallel chains. In addition, crystals of the complex were also investigated with thermogravimetry, vibrational spectroscopy (FTIR), and 13C CP-MAS NMR spectroscopy. The results obtained enabled us to structurally characterize the β-CD inclusion complex with p-HB.

Study of the Inclusion Compound Formed between a Luminescent Europium(III) β-Diketonate Complex and γ-Cyclodextrin

A 1 : 1 inclusion compound between γ-CD and the tris chelate complex Eu(NTA)3·2H2O [NTA = 1-(2-naphthoyl)-3,3,3-trifluoroacetone)] was prepared and characterized in the solid-state by powder X-ray diffraction, thermogravimetric analysis, FTIR, 13C CP MAS NMR and photoluminescence spectroscopy. Possible host-guest interaction geometries were generated from ab initio calculations. The photoluminescence results reveal the presence of a metal-to-ligand energy transfer that is much more efficient than that previously reported for the analogous β-CD adduct.

Analysis of the microcrystalline inclusion compounds of triclosan with β-cyclodextrin and its tris-O-methylated derivative.

Solid 1:1 inclusion compounds of triclosan with native and permethylated β-cyclodextrin (β-CD and TRIMEB) were prepared by co-crystallisation and co-evaporation, respectively, and studied by FT-IR and (13)C{(1)H} CP/MAS NMR spectroscopies, thermogravimetric analysis, X-ray diffraction and theoretical calculations. Results showed that triclosan inclusion into TRIMEB afforded an amorphous solid, whilst β-CD·triclosan is composed of microcrystals belonging to two different phases. In the phase featuring larger crystals, X-ray diffraction was carried out and the β-CD host units, packing head-to-head in infinite channels, were refined; the geometry for the included but highly disordered triclosan molecules was assessed by theoretical calculations. The bacterial growth inhibitory action of the inclusion compounds was studied in comparison to that of pure triclosan on Gram-negative (Salmonella, Escherichia) and Gram-positive strains (Bacillus, Listeria, Enterococcus and Staphylococcus) typically associated with human pathologies, and also on environmental bacteria isolated from different soil and water sources. The antimicrobial activities obtained in the present work showed that, of the two CD hosts, TRIMEB brings the most favourable carrier effect: it reduced the toxicity of triclosan against some of the environmental strains and afforded slightly higher action against virulent strains.

Encapsulation of sodium nimesulide and precursors in β-cyclodextrin

Crystalline 1 : 1 inclusion complexes with β-cyclodextrin (β-CD) and the sodium salt of nimesulide (4-nitro-2-phenoxymethanesulfonanilide), and the sodium salt of the derivative 2-phenoxymethanesulfonanilide, have been prepared by co-precipitation from aqueous solution. The presence of true inclusion complexes was supported by elemental analysis, thermogravimetry and powder X-ray diffraction. FTIR and 13C CP MAS NMR spectroscopy confirmed that no chemical modification of the guests occurred upon formation of inclusion complexes. The reaction of the precursors 2-phenoxynitrobenzene and 2-phenoxyaniline with β-CD was also studied and crystalline inclusion complexes with a 2 : 1 (host-to-guest) stoichiometry were isolated. The interaction of the different guest species with β-CD host molecules was studied theoretically by carrying out ab initio calculations. Favourable inclusion geometries were obtained for the four guests mentioned above. On the other hand, it was found that the inclusion of the neutral guests nimesulide and 2-phenoxymethanesulfonanilide was considerably less favourable. This is in agreement with the experimentally observed difficulty in isolating true inclusion complexes containing these guests and β-CD. The calculated lower stability is attributed to the different steric hindrance arising from the different conformational preferences of neutral and anionic forms.

Studies on polymorph conversion in a new cyclodextrin inclusion compound

A novel β-cyclodextrin (βCD) inclusion compound was prepared using 4-phenylpyridine-N-oxide (PPNO) as the organic guest. The inclusion compound, βCD·PPNO, was characterised both in solution and in the solid state using numerous techniques. 1H NMR in aqueous solution allowed the determination of a 1:1 stoichiometry and an association constant of 164 ± 21 M−1. Powder and single-crystal X-ray diffraction studies showed the formation of two distinct crystal phases, appearing at different timings. Over time, one of the crystal phases converts spontaneously into the other. This work is the first to monitor the conversion of different polymorphs of cyclodextrin inclusion compounds in real time.