Introduction to metal-organic frameworks and their applications in chemical sensing
1.6 Key features of MOFs for fluorescence sensing and bio-imaging
A fluorescent sensor must have desired selectivity, sensitivity, fast response time, material stability and reusability. MOFs exhibit unique characteristic features to become excellent chemical sensors. The porous structures of MOFs can potentially preconcentrate the analytes to gain enhanced sensitivity towards particular analyte. The key features of MOFs to act as a luminescent sensor material is described below:
1.6.1 Predictable structures
Fluorescence properties of MOFs greatly depended on the structural arrangement and intermolecular packing of the compounds for their energy transfer. Hence, it is very much important to control the three-dimensional structure and intermolecular packing at the molecular level. However, during construction of solid-state inorganic materials, the chemical driving force is ionic bonding which is very strong and thus the solid-state syntheses of inorganic materials at high temperatures generally lead to the formation of inorganic solid materials without predictable structures. Hence, the preparation methods for inorganic solid materials have been criticized as the “shake and bake”, “mix and wait”, and “heat and beat” methodology.144 The bond connectivity within organic molecules and metal-organic complexes is predictable but the overall three-dimensional packing structures of such types of compounds are still not predictable because some weak intermolecular interactions such as hydrogen bonding, van der Waals interactions and aromatic π-π interactions are there to control the overall 3D molecular packing.145 The bond energy of the coordination bonds in MOF materials is moderate, which allows the reversible formation and breaking of chemical bonds during the syntheses of MOFs, allowing the formation of thermodynamically stable MOFs. In situ formed metal- containing clusters (generally termed as secondary building units (SBUs)) have some preferential co-ordination geometries. Moreover, the 3D connectivity of these metal ions and/or metal-containing clusters (as the nodes) with organic linkers of predetermined shapes has led to the construction of MOFs with a higher degree of predictable structures.146
1.6.2 Processability in nanoscale
Nanoscale MOFs are needed for the application in the fields of biology, drug delivery and biomedical imaging.147 Actually, without nanoscale dimension, the internalization of the material into cells is not possible. The nano-MOFs show different or at least enhanced properties compared to bulk materials due to the high surface-to-volume ratio and quantum size effects. In addition, unique size-dependent optical, electrical and magnetic properties are also shown by nano-MOFs.
The nano-MOFs cannot be achieved by using conventional synthetic routes such as hydrothermal/solvothermal methods or slow diffusion method. Moreover, the conventional routes have several limitations on scaling up. Therefore, alternative methods such as the microwave assisted method, sonochemical and electrochemical methods have
been successfully introduced for synthesis of nano-MOFs.148 Actually, microwave radiation and ultrasounds accelerate the nucleation process and increase the seed number which basically inhibits the growth of MOF crystals. Moreover, self-assembly of nano- MOFs can be confined into droplets by microemulsion and can have great control on the surface of substrates by templates.
Typically, sizes of nano-MOFs lie on the 100 nm scale, with few extending below 20 nm.149 But, it has been well established that particles having size nanometer to micro- meter can be taken up by mammalian cells.150, 151 In the earlier time, nano-MOFs were mainly focused for drug delivery and bioimaging.152, 153 As the nano-MOF science progresses, more functional nano-MOFs are developed for medical applications. For example, the porphyrin or porphyrin derivatives-based nano-MOFs are proved to be very efficient in photodynamic therapy (PDT) of cancers, which can overcome the self- aggregation of porphyrin molecules in physiological conditions.154, 155 Although the nano- MOFs for biomedical applications are still in the preclinical stage, some Fe and Zn-based nano-MOFs have shown good response in medical application due to their low toxicity and high therapeutic effect.156 We expect the development of excellent nano-MOFs for clinical applications in near future.
1.6.3 Biocompatibility of MOFs
Biocompatibility is a property of a material, which means a material is not harmful for living tissue.157 Biocompatibility is an important factor in design and synthesis of MOFs for biomedical applications. Biocompatible MOFs should have endogenous linkers which are bio-friendly and non-toxic in nature.158 In addition to the choice of non-toxic ligands, choice of metal ions is also an important factor for the synthesis of biocompatible MOFs. According to the toxicological studies, some metals (e.g. Ca, Mn, Fe, Zn, Mg and Zr) are regarded as biocompatible ions for biological applications due to their considerable high lethal-dose levels of at least 1g kg-1.159-161
Biocompatible MOFs are generally applied in the field of bioimaging and drug delivery. Some Gd3+-, Mn2+- and Fe3+-containing MOFs showed great efficiency for bioimaging.156 Due to the relatively greater biological toxicity of Gd ions, Mn2+-based MOF contrast agents have been gradually developed because of the lower toxicity of Mn2+
than that of Gd3+.162, 163 Furthermore, two kinds of MOFs with UiO-66 structure containing high contents of Zr (37 wt%) and Hf (57 wt%) were reported. They are functionalized by silica and PEG, and exhibited high performance as CT contrast agents for spleen (131 HU)
or liver (86 HU) imaging.164 MOF materials are also excellent candidates to deliver drugs due to their good biological safety and inherent porosity. In addition, the biggest advantage of MOFs as drug carrier agent is not only the high drug loading capacity, but also the long drug release time. Ferey et al. first encapsulated ibuprofen in a MOF in the year 2006.
Ibuprofen has been utilized as a model drug in this study.157 In 2010, Horcajada et al.
reported the use of a series of non-toxic porous Fe(III)-MOFs, i.e. MIL-53, MIL-88A, MIL-88Bt, MIL-89, MIL-100 and MIL-101-NH2, as carriers of antineoplastic and retroviral drugs, including busulfan, azidothymidine triphosphate, doxorubicin, cidofovir, ibuprofen, caffeine, urea etc.165 Despite the concern on the stability of MOFs, the stability was reported to be significantly improved by coating polymer materials. For example, coating polydimethysiloxane (PDMS) on the surface of MOF materials can greatly enhance their moisture or water resistance. However, some of MOFs are also focused for oral administration and in-vivo application.166 In future, continuous efforts need to be focused on biostability, biocompatibility and practicability to realize the full clinical applications of MOFs.
1.6.4 Collaborative luminescence properties
Fluorescent MOF materials are somehow different from other traditional inorganic and organic luminescent compounds for their potentially collaborative multifunctionalities. The organic moieties, metal centers, metal-organic charge transfer and guest molecules within MOFs can potentially generate luminescence.167 All such interesting features help to develop MOFs as great luminescent materials. The permanent porosities and collaborative luminescent properties of MOFs are particularly useful to develop luminescent sensing materials for recognition of partcular analytes.168, 169 Actually, judicial choice of metal ions and fine tuning of functional groups in MOFs can bring special properties in MOFs which enhance the detection abiliy of MOFs towards particular analyte. Several luminescent MOFs have been successfully employed for sensing and bioimaging applications.170-172