In the continually changing field of drug delivery, it is all about generating novel and effective materials. Among the promising candidates that have caught the researchers' imagination is 2,7-dibromo-9H-fluorene, a halogenated version of fluorene. It has a unique structural and electronic composition that makes it especially well-suited for numerous biomedical applications, especially drug delivery. Research and use of 2,7-dibromo-9H-fluorene also open the possibility of new forms of drug delivery vehicles, for better pharmacokinetics and specificity of drugs. 2,7-Dibromo-9H-fluorene has a polycyclic aromatic moiety, reinforced with bromine at the 2 and 7 positions. This arrangement not only gives the drugmolecule considerable stability, but also greatly increases its electron-retraction capabilities, making it a good candidate for conjugation with an eclectic range of drugs. These bromine atoms on the fluorene backbone can be used to target specific locations for functionalisation, and can be used to make high-tech drug delivery systems that address specific medical requirements. And the hydrophobic property of the fluorene layer is especially useful for packaging hydrophobic medicines to prevent their premature breakdown and increase their bioavailability. There are numerous benefits from adding 2,7-dibromo-9H-fluorene to drug delivery systems. For one, its ease of chemical manipulation means it can be made into controlled release delivery vehicles so that the drug gets to the right place and the right amount at the right time, with minimal side effects and the best possible therapeutic effect. Second, the photophysical effects of fluorene derivatives — fluorescence for example — can be used to monitor and image drug delivery processes in real-time, which are critical to understand the biodistribution and efficacy of the therapy. Third, fluorene-based materials are biocompatible and not toxic in high concentrations – hence suitable for clinical use, which means patient safety and compliance.
Figure 1. Synthesis of new 2-7-dibromofluorene and benzocyclobutene derivatives. Reagents and condition. (Konstantine S. L. et al.; 2020)
The structure stiffness and electronic flexibility make 2,7-dibromo-9H-fluorene one of the most special drug delivery materials. The bromine substituents make the compound more reactive and a perfect candidate for functionalization with other drug molecules and targeting ligands. Such flexibility makes it possible to engineer multi-target drug delivery systems capable of multiple targets at once. Conjugates of 2,7-dibromo-9H-fluorene with antibodies or peptides, for example, can form targeted delivery systems that recognise and bind to cancer cells, improving the precision and effectiveness of anticancer therapies. This second interesting property of 2,7-dibromo-9H-fluorene are the photophysical properties. Fluorene derivatives have an abundance of fluorescence, which can be used to image and monitor the delivering of drugs in real time. This is especially useful when we are trying to track the biodistribution and release timing of therapeutics, and see how treatment is doing in real time. Such data are invaluable for controlling drug dosage and timing so that patients receive better, more targeted medical treatment. 2,7-dibromo-9H-fluorene can be also applied to the target delivery and imaging systems as well as stimuli-sensitive drug delivery systems. The electronic structure of the compound can be controlled according to external factors (eg pH, temperature, light). Such flexibility can be used to build smart drugs that deliver payloads on the basis of a physiological state or trigger. So, for instance, a pH-sensitive drug delivery system could deliver its drug cargo into an acidic tumor site so that the drug concentrates at the site of action, and is as minimally distributed as possible in the system as well as in the adverse effects. This versatility is not only useful for drug delivery, but also in the area of theranostics — which unites therapy and diagnostics under one roof. Fluorescence from the nature of fluorene derivatives could be used to see and track the therapeutic action – a dual utility, which in personalised medicine is in short supply. When therapeutics and diagnostic markers are contained in the same delivery vehicle, 2,7-dibromo-9H-fluorene platforms could provide a one-stop disease management solution that allows monitoring in real time and immediate response to the treatment program. 2,7-dibromo-9H-fluorene is another very old bromination reaction, involving fluorene. The reaction normally uses bromine or NBS (without catalyst) in a solvent to brominate selectively at the 2 and 7 positions. This controlled synthesis allows 2,7-dibromo-9H-fluorene to be purified and yielded at a very high purity in order to be functionalized for use in the delivery of drugs. Functionalisation of 2,7-dibromo-9H-fluorene consists of inserting functional groups or molecules on to the fluorene backbone. We can do so by chemical processes such as Suzuki coupling, Heck reaction and Sonogashira coupling. Such reactions allow multiple functional groups (amines, carboxylates, thiols) to be bonded to drug molecules, targeting ligands or other bioactive molecules. With these functionalisation options available, it becomes possible to develop tailor-made drug delivery systems with tailored properties to suit particular therapeutic requirements. For example, we can use Suzuki coupling to add aryl or heteroaryl groups to the 2,7-dibromo-9H-fluorene structure, making it more electronic and easier to conjugate with drugs. In the same manner, Heck and Sonogashira reactions can be attached to alkene or alkyne groups respectively, giving further places to modify. Such functionalizations not only extend chemical diversity of 2,7-dibromo-9H-fluorene derivatives but also make it possible to finely tune their physicochemical and biological properties for the best drug delivery.
This hydrophobic backbone of fluorene in 2,7-dibromo-9H-fluorene is especially convenient for hydrophobic drugs. The result of this encapsulation is usually micelles, nanoparticles or other nanoscale structures where the hydrophobic drug molecules are trapped in the hydrophobic core, and the hydrophilic structure interacts with the surrounding watery environment. This configuration helps the drug molecules from being damaged prematurely, and makes them more solubile and bioavailable. The exit of the encapsulated drug from the 2,7-dibromo-9H-fluorene carrier can be modulated by diffusion, degradation and stimulation. Diffusion release is based on the drug molecules being gradually diffused out from the hydrophobic core into the media. This is adjustable through the composition and shape of the delivery vehicle, with continued or monitored release for a period of time. Degradation-based release results from the disintegration of the structure of the delivery vehicle, as a result of enzyme or chemical reactions in the living system. This is especially useful for site-directed drug release, because the degradation can be programmed to happen in a physiological state that's regulated by a physiological state, such as the acidic pH of a tumor cell microenvironment or a certain enzyme. Through the engineering of the degradation characteristics of the delivery system, it is possible to deliver the drug at the targeted site of action, with the greatest therapeutic impact and least systemic side effects. Release-based on stimulus: these release mechanisms are made by utilizing the unusual electronic structures of 2,7-dibromo-9H-fluorene in response to external stimuli like light, temperature or magnetic fields. For instance, light-sensitive devices could be designed to release the encapsulated drug upon receipt of a certain wavelength of light, which would be a non-invasive and accurate means of regulating drug release. Similarly, temperature- or magnetically-sensitive devices can be programmed to release the drug upon local heating or by using a magnetic field, which provides further flexibility in when and where the drug is delivered.
Alternate Names:
2,7-Dibromo-9H-fluorene
9H-Fluorene, 2,7-dibromo-
2,7-Dibromo-fluorene
2,7-Dibromofluorene
Dibromo-9H-fluorene
2,7-Dibromofluorene
References:
1. Konstantine S. L. et al.; Synthesis of new 2,7-dibromo 9-benzocyclobuten-3-yl-9H-fluorene derivatives - perspective dielectric materials for electronics. IOP Conference Series Materials Science and Engineering. 2020, 734(1):012127.
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