The purpose of this study was to prepare and characterize of holmium-beta-cyclodextrin complex (Ho-<i>β</i>-CD) in order to increase the solubility and stability of Holmium. To achieve this goal, Ho-<i>β</i>-CD complex was prepared by evaporation method of holmium and beta cyclodextrin solutions in a proportion (1:1) and (1:3), respectively. Infrared (IR) and Raman spectroscopy, X-Ray Diffraction were performed to identify the complex. Morphology of the Ho, <i>β</i>-CD, and Ho-<i>β</i>-CD were studied using Scanning Electron Microscopy (SEM).
Lanthanide series may be divided into two groups: the light lanthanide elements (La, Ce, Pr, Nd, Pm, Sm, Eu) and the heavy rare elements (Gd, Tb, Dy, Ho, Er Tm Yb, Lu) [
Recently, in the pharmaceutical industry has appeared on the some novelmetaldrugs containinglanthanidecationswith potentialpharmacological application sessentially based on its similarity tocalcium. The lanthanides for their size and electronic structure have some unique characteristics that make them suitable for certain the rapeutic purposes and as diagnostic [
Among the radionuclide used for cancer therapy, 131I, 90Y, 188Re, 166Ho, or 153Sm are applied for the treatment of a multitude of malignant disorders; they have been used for cancer therapy, palliation of bone pain arising from secondary metastases, radio-synovectomy or intravascular radiation therapy [
166Ho is used in nuclear medicine for the therapy of arthritis by radiation synovectomyfor bone marrow ablation, and in the study of immunospecific radiopharmaceuticals, among others [
Several lanthanide complexes formed with acyclic and cyclic ligands have been prepared and evaluated for radiopharmaceuticals applications [
Cyclodextrins (CDs) are cyclic oligosaccharides (α-1,4)-linked of α-D-glucopyranose containing a relatively hydrophobic central cavity and hydrophilic outer surface. The most common cyclodextrins are α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin which contain 6, 7 and 8 glucopyranose units respectively. The melting point of α, β and γ-cyclodextrin are between 240˚C and 265˚C consistent with their stable crystal lattice structure [
Cyclodextrins are widely used in various fields of pharmaceutical industry such as drug delivery, stabilization of drugs, additives in the biotechnology and analytical methods etc. Cyclodextrins increase the water solubility of poorly soluble drugs and improve their bioavailability. Light thermal and oxidative stability of actives can be improved through the formation of cyclodextrin complexes [
In particular, the β-cyclodextrin, have a limited aqueous solubility (has the highest solubility of the CDs), and their complex formation with lipophilic drugs, and other compounds with limited aqueous solubility, frequently gives rise it [
In this context, both holmium and beta cyclodextrin hold a distinctive place for all uses and applications that have been mentioned, consequently, is important to prepare inclusion complex holmium-betacyclodextrinto improve these pharmaceutical applications mainly.
For these reason, the aim of the present research was to prepare and characterize of inclusion compound Holmium-β-cyclodextrin.
All the chemical compounds were grade analytical, used as obtained, and solutions were prepared with distilled water. β-Cyclodextrin (β-CD), with molecular formula of C42H70O35 and molecular weight of 1134.98 g/mol, and Holmium Nitrate pentahydrate (Ho(NO3)3∙5H2O) with molecular weight of 382.56 g/mol, both were obtained from Sigma-Aldrich Company, Inc. Ethylene dinitrilotetraacetic acid disodium salt dehydrates (EDTA) and Xylenol orange were obtained from Merck Company.
β-cyclodextrin was dissolved in distilled water and stirred for 30 minutes by sonication with Cole Parmer Ultrasonic equipment 8891 (Illinois, USA). The concentration of this solution was 0.002 M.
On the other hand, Holmium Nitrate pentahydrate was dissolved in 10−3 M hydrochloride acid. The concentration of holmium (HO(NO3)3∙5H2O) in the standards solution was determined by titration with a 0.025 M EDTA solution. Three drops of pyridine and 3 drops of xilenol orange were also added. The holmium concentration in the standard solution was 0.4 M.
The inclusion complex of holmium with β-cyclodextrin (further abbreviated as Ho-β-CD) was prepared as following: solution of β-cyclodextrin was mixedwith standard solution of the holmium in the molar ratio 1:1Ho:β- CD or 1:3Ho:3β-CD, and stirred for 30 minutes by sonication. The result solution was slowly evaporated to dryness on a grill heating (Plate-Stirrer, Corning PC-351). Ho-β-CD obtained was washed with water and dried in an oven LAB-LINE Instrument at 60˚C for 2 hours.
The Ho-β-CD inclusion complex was examined by infrared spectroscopy, Raman spectroscopy, X-Ray Diffraction, elemental analysis and scanning electron microscopy (SEM).
Scanning electron microscopy (SEM) and elemental analysis
Surface morphology of Ho-β-CD was evaluated by scanning electron microscopy using a Philips XL30 FEGSEM. A voltage of 5 to 10 kV was applied. Samples of β-Cyclodextrin, Holmium Nitrate pentahydrate, and Ho-β-CD were mounted onto aluminium stubs and sputter-coated with agold layer of about 10 mm. These samples were analyzed by an energy dispersive X-ray spectrometer (EDX).
A UV-Vis spectrophotometer (Perking Elmer UV-Vis lambda 10) with 1 cm quartz cells was used for all following spectroscopic studies. The absorption vs. wavelength profiles were obtained in the range of 200 - 700 nm.
Infrared spectroscopies were recorded on a Nicolet Magna-IR 550 FT-IR spectrometer (Madison, Wiscosin, USA), in the range of 400 - 4000 cm−1. Samples of β-Cyclodextrin, Holmium Nitrate pentahydrate, and Ho-β- CD were prepared by mixing with spectroscopy grade KBr grain. The KBr mixture was then pressed into a pellet. In addition to solid state IR experiments, samples were analyzed.
X-Ray Diffraction experiments were carried out by diffraction solid state X-ray equipment with powder diffractometer Siemens D-5000, with copper anode, λ = 1.5406 Å. The samples of the inclusion complex of Ho-β-CD (1:1), Ho-β-CD (1:3), [Ho(NO3)3∙5H2O], and β-cyclodextrin were placed in a specimen, it was introduced into a goniometer to which a beam made of X-ray, obtaining a graph of intensity against diffraction angle with a sweep of 4˚ to 70˚ 2θ. The results obtained were compared to cards patterns reported by the Joint Committee on Powder Diffraction Standards (JCPDS) to verify the presence of the material studied.
Raman spectroscopy was performed on a Kaiser RXN spectrometer equipped with a 70 mW 785 nm diode laser for excitation, a holographic grating for dispersion and a peltier cooled Andor CCD camera for detection.
Raman spectroscopy was done using a Horiba-JobinYvonLabRamHR VIS high resolution confocal Raman microscope system with 633 nm laser.
In
In the case of Ho-β-CD can be seen is different from morphology reagents separately. It is obvious that Holmium-β-cyclodextrin Inclusion complex 1:1 and 1:3 are present Ho and β-CD according at differing rates. This suggested the Ho molecules are included in the β-CD inclusion complex.
EDS analysis in 10 different point of each sample to obtain an average of the elements constituting of each of these materials, shows the presence of several elements, the most abundant, holmium, nitrogen, carbon, oxygen, among others. The results are shown in
The carbon in Ho(NO3)3∙5H2O is due at CO2 of the environmental. This compound is very hygroscopic. This effect was observed in the FTIR studies (absorption band 2362.72 cm−1), too.
Element | Samples | |||
---|---|---|---|---|
Ho(NO3)3∙5H2O | β-CD | Ho-β-CD (1:1) | Ho-β-CD (1:3) | |
C | 15.40 ± 4.5 | 58.66 ± 1.54 | 50.86 ± 10.93 | 57.11 ± 4.20 |
O | 67.04 ± 1.38 | 41.34 ± 1.54 | 47.09 ± 9.42 | 41.56 ± 5.11 |
Ho | 5.45 ± 3.79 | 2.06 ± 1.89 | 1.32 ± 1.03 | |
N | 12.11 ± 1.40 |
Absorption spectra shape for Ho(NO3)3∙5H2O) and Ho-β-CD inclusion complex were similar, but, the absorbance of Ho-β-CD inclusion complex was higher than that of Ho(NO3)3∙5H2O alone, due to the formation inclusion complex between Ho(NO3)3∙5H2O and β-CD. The same phenomena have been observed by Kavirajaa et al. and Wang et al. [
The presence or absences of characteristic peaks associated with specific structural groups of the molecules were noted. The frequencies for pure β-cyclodextrin observed at 3395.3 cm−1, 2924.96 cm−1, 1156.52 cm−1, and 1030.16 cm−1 which corresponds to the symmetric and antisymmetric stretching of ˅[OH], ˅[CH2], ˅[C-C], and bending vibration of ˅[O-H] respectively. Meanwhile, IR spectrum of Ho(NO3)3∙5H2O (
lead to the formation of hydrogen bonding and the presence of Vander Waals forces during their interaction to form the Ho-β-CD inclusion complex.
On the other hand, the FTIR spectrum of the Ho-β-CD inclusion complex imitated the characteristic peak of the β-CD and the Ho(NO3)3∙5H2O, which can be regarded as a simple superimposition of those host and guest molecules. Thus, the FTIR spectra significantly prove the formation of Ho-β-CD inclusion complex [
Furthermore, the absorption bands 1440, 1374, and 1341 cm−1 of the β-CD disappear (
Functional group | Wavenumber (cm−1) | ||
---|---|---|---|
β-CD | Ho-β-CD inclusion complex | Changes Δδ | |
˅[OH], Symmetric and antisymmetric | 3395.3 | 3393.69 | −1.61 |
˅[CH2], | 2924.96 | 2928.22 | −3.26 |
˅[C-C], | 1156.52 | 1156.86 | 0.37 |
˅[O-H] Bending vibration | 1030.16 | 1029.47 | −0.69 |
Functional group | Wavenumber (cm−1) | ||
---|---|---|---|
Ho(NO3)3∙5H2O | Ho-β-CD inclusion complex | Changes Δδ | |
˅[OH], | 3398.37 | 3393.69 | −4.68 |
δ[OH of HOH] | 1633.04 | 1638.92 | 5.68 |
δ[NO3] | 1482, 1384.65, 1041.58, 819.61, 747.87 |
it is observed in the Ho-β-CD inclusion complex (at 1387 cm−1) (
Another method commonly used to study the reagents(Holmium Nitrate Pentahydrate and β-cyclodextrin) and Holmium-β-cyclodextrin inclusion complex is XRD. The X ray diffraction spectra of reagents (Ho(NO3)3∙5H2O and β-CD)and Ho-β-CD inclusion complex are showed in
The diffraction pattern of the Ho-β-CD inclusion complex was found to be different than diffraction pattern of pure β-CD and Ho(NO3)3∙5H2O. Comparing the pattern for Ho-β-CD inclusion complex with that pure compound revels mark difference. In complex, the new peaks were found and shift in peak position also where found and have peaks which are superimposition of two individual. The intensity of new peaks confirms complex formation.
The insertion of the guest molecule into the cavity of the β-CD will result in the chemicals shift of guest and host molecule in the Raman spectra. In
The Raman spectrum obtained in the analysis of the of the β-cyclodextrin, inclusion complex Ho-βCD, and Ho(NO3)3∙5H2O can be observed in
The formation of Holmium-β-cyclodextrin inclusion complex has been achieved. The morphology of the samples is evaluated, which indicates that the chemicals compositions of the inclusion complex formed. FTIR and Raman confirm the presence of Ho in the complex β-CD, while XRD results suggest that the two components form Holmium-β-cyclodextrin inclusion complex. This result opens up excellent opportunity to use these materials in internal selective radiotherapy.