Optimized synthesis and crystalline stability of γ-cyclodextrin metal-organic frameworks for drug adsorption

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Abstract

The biocompatible and renewable cyclodextrin metal-organic frameworks (CD-MOFs) have addressed a range of opportunities in molecular storage and separation sciences. The reported protocols for their synthesis, however, were carried out at room temperature over long time periods of time (24 h), producing crystals of relatively poor uniformity. In this investigation, micron sized γ-CD-MOFs were synthesized by an optimized vapor diffusion method at elevated temperature (50 °C) within 6 h, after which the size control, crystalline stability and drug adsorption behavior were investigated in detail. In this manner, uniform cubic γ-CD-MOF crystals were obtained when the reaction temperature was raised to 50 °C with pre-addition of the reaction solvent. The size of γ-CD-MOFs was adjusted efficiently by changing the reactant concentrations, temperatures, time, γ-CD ratios to KOH and surfactant concentrations, without influencing the porosity and crystallinity of the material markedly. Varing degrees of reduction in crystallinity and change in morphology were observed when the γ-CD-MOF crystals are treated under conditions of high temperature (100 °C), high humidity (92.5%) and polar solvents (e.g., MeOH and DMF). In relation to drug adsorption by γ-CD-MOFs, most of the drug molecules containing carboxyl groups showed relatively high adsorption (>5%), while low adsorption (<5%) was found for drugs with nitrogen-containing heterocyclic rings. In addition, the adsorption kinetics of captopril to standard γ-CD-MOFs matched a pseudo-second-order model rather well, whilst captopril adsorption to the damaged γ-CD-MOFs only partially matched the pseudo-second-order model. In summary, based upon the optimized synthesis and size control of γ-CD-MOFs, the crystalline stability and drug adsorption characteristics of γ-CD-MOF crystals have been evaluated as a fundamental requirement of a potential vehicle for drug delivery.

Introduction

Metal-organic frameworks (MOFs), also known as porous coordination polymers, have emerged as a new class of porous materials for diverse applications such as molecular recognition (Jiecheng et al., 2014, Kumar et al., 2014, Liao et al., 2014), gas storage (Ghose et al., 2015, Kumar et al., 2015, Wen et al., 2012), separation science (Kılıç et al., 2015, Li et al., 2014, Manju et al., 2014), catalysis (Li et al., 2012, Song and Lin, 2012) and drug delivery (Miller et al., 2010, Yun et al., 2013). Usually, they are highly tunable hybrid materials crafted from metal connecting points and organic bridging ligands (Li et al., 1999) with predictable extended structures.

Since the biocompatibility of materials is essential for most potential biological applications, the metals and organic bridging ligands of MOFs have to be bio-friendly. Estimated from the toxicity parameter LD50, some metals such as Ca, Fe, Zn, K, and Ti are considered to be biologically acceptable (Horcajada et al., 2012) and therefore more attention has been paid to biomolecules as linkers of biological active MOFs for biological applications. In addition, natural linkers such as amino acids (Yang et al., 2015), nucleobases (Thomas-Gipson et al., 2015), peptides (Ikezoe et al., 2012), glutarates (Jhung et al., 2006), carbohydrates (Chen et al., 2014), oxalates (Chih-Min and Kwang-Hwa, 2009) and succinates (Cheng et al., 2010) have been reported as being suitable to bind metal ions to form functional porous MOFs.

Recently, the environmental friendly and renewable cyclodextrin (CD) metal-organic frameworks (CD-MOFs) obtained from γ-CD and potassium ions employing a vapor diffusion method have been reported (Forgan et al., 2012, Furukawa et al., 2012, Gassensmith et al., 2011, Smaldone et al., 2010). The γ-CD-MOFs are body-centered cubic structures with apertures of 7.8 Å and have large spherical voids with diameters of 17 Å, linked by coordination of the –OCCO– units located on the D-glucopyranosyl residues of γ-CD to the potassium cations. The extended frameworks of CD-MOFs are connected by numerous channels with a calculated pore volume of 54% (Smaldone et al., 2010). Among the various MOFs reported to date, γ-CD-MOFs are potential materials for gas adsorption (N2, H2, CO2 and CH4) and the sequestering of some small molecules (Rhodamine B by co-crystallization and 4-phenylazophenol by adsorption) within their pores (Smaldone et al., 2010). Taking advantage of the cavities of diameter 1.7 nm and the high local concentrations of the OH ions, a γ-CD-MOF-based template strategy has been developed (Wei et al., 2012) for the synthesis of silver and gold nanoparticles. The γ-CD-MOFs have also been employed to address the challenging separation and purification requirements of petrochemical feedstocks on account of the fact that their three dimensional transverse channels exhibit superior separation features and high resolutions in comparison with other extended framework materials (Holcroft et al., 2015).

On account of the weak noncovalent bonding interactions between the building blocks and metal centers, the parameters employed in the synthesis, including solvent, metal source, molar ratio of reactants, temperature and duration, have a major influence on the physiochemical properties of CD-MOFs. The preparation of pure, homogeneous and monodisperse crystals is critically important in relation to the potential applications of MOFs. Among the studies devoted to the preparation and application of CD-MOFs (Joong et al., 2011, Khan and Kang, 2011, Stock and Biswas, 2012), the crystalline stability of the materials also showed their effectiveness in the generation of families of porous materials. Very few systematic studies, however, have focused on the chemical, thermal and hydrothermal stabilities of MOFs or γ-CD-MOFs (Cychosz and Matzger, 2010).

In this investigation, γ-CD-MOF crystals were obtained by an optimized vapor diffusion method within a short production time, and the characterization, stability and drug adsorption performance were investigated. The γ-CD-MOF crystals prepared under conditions with different reactant concentrations, temperatures, time, molar ratios of γ-CD to KOH, solvents and surfactants were optimized with reference to their shape and size. The crystalline stability of the γ-CD-MOF crystals produced under different processing conditions was probed primarily using PXRD and SEM. Furthermore, preliminary studies were carried out on the adsorption of 21 drugs to γ-CD-MOFs as well as their adsorption behavior.

Section snippets

Materials and reagents

γ-cyclodextrin was obtained from Maxdragon Biochem Ltd (China). Potassium hydroxide (KOH), cetyl trimethyl ammonium bromide (CTAB), methanol (MeOH), absolute ethanol (EtOH), isopropanol (iPrOH), acetone (Me2CO), dichloromethane (DCM) and N,N-dimethylformamide (DMF) were of analytical grade and purchased from Sinopharm Chemical Reagent Co. Ltd (China). All drugs (>99.5% purity) were purchased from Dalian Meilun Biotech Co., Ltd (China). Pure H2O (18.4  cm), used in all experiments was purified

Optimized synthesis of micron sized γ-CD-MOFs

A vapor diffusion method has been reported (Smaldone et al., 2010) for the synthesis of γ-CD-MOFs, prepared by dissolving γ-CD (1.30 g, 1 mmol) along with KOH (0.45 g, 8 mmol) in aqueous solution (20 mL), followed by vapor diffusion with MeOH at ambient temperature over the period of a week to produce γ-CD-MOFs as cubic crystals of 40–500 μm in size. A modified method with the addition of CTAB and a controlled incubation time about 26–32 h has been reported (Furukawa et al., 2012) to produce the

Conclusions

In this investigation, a fast solvent evaporation approach was developed to synthesize and tailor the γ-CD-MOFs to a controlled size, with the synthesis period shortened from that reported in the literature of over 26 to 6 h. The size of γ-CD-MOF crystals was adjusted by altering the reactant concentrations, reaction temperatures, reaction time, ratios of γ-CD to KOH and surfactant concentrations, without any marked changes in particle crystallinity and porosity. And the γ-CD-MOF crystals of

Acknowledgements

We are grateful for the financial support from National Science and Technology Major Project (2013ZX09402103) and National Natural Science Foundation of China (81373358). This research is also part of the Joint Center of Excellence in Integrated Nano-Systems (JCIN) at King Abdulaziz City for Science and Technology (KACST) and Northwestern University (NU). The authors would like to thank both KACST and NU for their continued support of this research.

References (46)

  • Ramos-Fernandez et al.

    MOFs meet monoliths: hierarchical structuring metal organic framework catalysts

    Appl. Catal. A Gen.

    (2011)
  • M. Walker et al.

    Ammonia removal in anaerobic digestion by biogas stripping: an evaluation of process alternatives using a first order rate model based on experimental findings

    Chem. Eng. J.

    (2011)
  • T. Brar et al.

    Control of crystal size and distribution of zeolite A

    Ind. Eng. Chem. Res.

    (2001)
  • J. Chen et al.

    Conversion of fructose into 5-hydroxymethylfurfural catalyzed by recyclable sulfonic acid-functionalized metal–organic frameworks

    Green Chem.

    (2014)
  • W. Chih-Min et al.

    Synthesis of novel organic-inorganic hybrid compounds: lanthanide phosphites incorporating a squarate ligand

    Inorg. Chem.

    (2009)
  • K.A. Cychosz et al.

    Water stability of microporous coordination polymers and the adsorption of pharmaceuticals from water

    Langmuir ACS J. Surf. Colloids

    (2010)
  • S. Diring et al.

    Controlled multiscale synthesis of porous coordination polymer in nano/micro regimes

    Chem. Mater.

    (2010)
  • R.S. Forgan et al.

    Nanoporous carbohydrate metal-organic frameworks

    J. Am. Chem. Soc.

    (2012)
  • Y. Furukawa et al.

    Nano- and microsized cubic gel particles from cyclodextrin metal–organic frameworks

    Angew. Chem. Int. Ed.

    (2012)
  • J.J. Gassensmith et al.

    Strong and reversible binding of carbon dioxide in a green metal-organic framework

    J. Am. Chem. Soc.

    (2011)
  • S.K. Ghose et al.

    Understanding the adsorption mechanism of Xe and Kr in a metal–organic framework from X-ray structural analysis and first-principles calculations

    J. Phys. Chem. Lett.

    (2015)
  • J.M. Holcroft et al.

    Carbohydrate-mediated purification of petrochemicals

    J. Am. Chem. Soc.

    (2015)
  • P. Horcajada et al.

    Metal-organic frameworks in biomedicine

    Chem. Rev.

    (2012)
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    These authors contributed equally to the manuscript.

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