5,5'-Diformyl-2,2'-bipyridine (DFBP) has become increasingly relevant in recent years as a possible linker to COFs in drug delivery systems. This molecule is relevant for chemical synthesis as it can be a monomer in the construction of COF molecules like Py-2,2'-BPyPh COF, BPy COF and Re-COF. That is, 5,5'-Diformyl-2,2'-bipyridine can bind to other organic molecules by Schiff base condensation reaction, resulting in very crystallinity and porosity COF structures. They're often employed for gas storage, adsorption, catalysis, chemical sensing and energy storage due to their high specific surface area, chemical and thermal stability. COF are crystal porous structures that are defined and customizable, which are perfect for applications like drug delivery. COF is an excellent surface area, stability and can hold a wide range of molecules including drugs which can be released controllably. DFBP is an organic bifunctional molecule with an aldehyde at the 5,5'-end of its bipyridine moiety that binds COF building blocks together. Because of its chemistry (and ability to coordinate with metal ions), it's an excellent tool for creating functional COFs with specific attributes, that could be used for encapsulating and selectively delivering drugs. DFBP as a COF linker is of particular interest for drug delivery systems that are highly stable, controlled release and want their surface to be altered to achieve effective targeting.
Figure 1. Structure and characteristics of TAPB-BPDA COF. (Run Chen, et al.; 2021)
The function of 5,5'-diformyl-2,2'-bipyridine in COF-based drug delivery systems is to allow for the establishment of a stable, covalently bonded structure. DFBP has two rings of pyridine bound together by a bipyridine bond and its reactive aldehyde functional groups are at the 5,5' position. These groups of aldehydes are cationically active, and DFBP can be part of condensation reactions to attach organics into a long-winded highly ordered network. This structural adaptability permits the synthesis of very porous compounds that could host many different types of drug delivery. For instance, by using DFBP in COFs, we can engineer a network that stores drugs within its pores, so that they don't break down too quickly and can be kept in check over time. Moreover, because DFBP can be co-ordinated with metal ions (eg, copper, zinc, platinum), it's possible to create Mofs with more stability and better controlled release mechanisms. These metal-organic COFs can hold anything from small molecules to biologics as an active compound, which then enables a stable, high efficiency way to deliver it to tissue. DFBP-based COFs for drug delivery deliver controlled and long-lasting release of the drug. Because of the porous nature of COFs, drugs can be trapped within their pores – a way of securing sensitive drugs against environmental damage. This is especially useful when transporting biologically active molecules like proteins or nucleic acids, which are not well-suited to stability in water. The size of the pores in DFBP-based COFs can be precisely controlled to hold different drugs, such as small molecules, macromolecules and nanoparticles, making these drugs even more flexible. And the secret to controlling drug release is in the COF design itself. The linkers based on DFBP, for instance, can be tailored to biological state (pH, temperature, enzyme, etc.). For cancer treatment, for example, the acidic tumor microenvironment might be what drives a chemotherapeutic release from a DFBP-based COF so that the drug would reach the tumor and cause minimal systemic toxicity. This capability to engineer COFs for controlled release gives it a distinct advantage over conventional drug delivery systems that may not be able to reach specific tissues or control release rates.
Not only can COFs be controlled to deliver drugs, they can be utilized to create multifunctional drug delivery systems. The reactive aldehydes on DFBP allow it to be functionalised with multiple molecules: target ligands, imaging molecules or other therapeutic molecules. With a change to the DFBP linker, the COF's functions can be adjusted for particular drug-delivery objectives. COFs can, for example, be engineered with ligands that attach to receptors on the surface of cancer cells, so that treatment can be delivered specifically to them. Being able to bind targeting ligands (monoclonal antibodies, peptides, etc.) to the surface of the COF is a big advantage for increasing the specificity and effectiveness of drug delivery. Such a targeted delivery does not only enhance the concentration of the drug in the target site, but also avoids off-target effects (a common issue with standard methods of drug delivery). Additionally, when imaging agents are added to the COF hull, the biodistribution of the drug delivery system can be monitored in real time. This simultaneous ability to be both diagnostic and therapeutic, in the same device, allows for the possible creation of theranostic systems in which both drug and the tracking of therapeutic effect can be delivered in parallel. DFBP-based COFs therefore have great promise for the next generation of personalized medicine, where the drug delivery system can be customisable to the needs of the patient. The other strength of DFBP-based COFs for drug delivery is the variety in the type of drugs delivered. 'Furthermore, most existing drug delivery technologies (liposomes, polymer nanoparticles, etc.) – can't handle some types of drugs, especially hydrophilic or large biomolecules (proteins, nucleic acids, vaccines). DFBP-based COFs, on the other hand, offer a flexible platform for encapsulating all types of therapeutic drugs (hydrophonic and hydrophilic). These massive surface area and variable pore sizes of COFs allow them to take on different drug molecules and the framework's strength ensures that these molecules stay safe when moving through the body. It is also possible to modify the architecture of COFs to accept a combination of drugs in a single system. A COF might deliver, for instance, both a chemotherapeutic and an RNA-based treatment like siRNA to a cancer cell. When DFBP is used as the linker position, we can design intricate multifunctional structures that not only transport the drugs but also will tune to biological signals so that they release the drugs in the right location and at the right time. Addition of 5,5'-Diformyl-2,2'-bipyridine to COFs is a novel, exciting mode of drug delivery. Its specificity to co-ordinate with metal ions, functionalize and develop stable covalent networks makes DFBP a prime candidate for highly configurable and malleable COFs. These are materials with many benefits such as the ability to package a large variety of therapeutics, give controlled release, and deliver only to certain tissues or cells. Moreover, if diagnostic and therapeutic functions can be integrated into one system, there are new opportunities to create theranostic platforms with the ability to track drug distribution and therapeutic outcome in real time. With this field of research still maturing, the possibilities for DFBP-based COFs as drug delivery mechanisms is vast and could increase efficacy, safety and specificity of therapies for many disease states including cancer, genetic disorders and infectious diseases.
Alternate Names:
5,5'-Biformyl-2,2'-bipyridine
5,5'-Diformylbipyridine
5,5'-Diformyl-2,2'-bipy
2,2'-Bipyridine-5,5'-dicarboxaldehyde
5,5'-Diformal-2,2'-bipyridine
5,5'-Bipyridine dicarboxaldehyde
5,5'-Diformal-2,2'-dipyridine
2,2'-Dipyridine-5,5'-dicarboxaldehyde
Bipyridine-5,5'-dicarboxaldehyde
References:
1. Run Chen, et al.; Stable nitrogen-containing covalent organic framework as porous adsorbent for effective iodine capture from water. Reactive and Functional Polymers. 2021, Volume 159, 104806.
Datasheet
