Mono-amine Functionalized Phthalocyanines: Microwave-Assisted Solid-Phase Synthesis and Bioconjugation Strategies

Abstract

Phthalocyanines (Pcs) are excellent candidates for use as fluors for near-infrared (near-IR) fluorescent tagging of biomolecules for a wide variety of bioanalytical applications. Monofunctionalized Pcs, having two different types of peripheral substitutents; one for covalent conjugation of the Pc to biomolecules and others to improve the solubility of the macrocycle, ideally suit for the desired applications. To date, difficulties faced during the purification of the monofunctionalized Pcs limited their usage in various types of applications. Herein are reported a new synthetic method for rapid synthesis of the target Pcs and bioconjugation techniques for labeling of the oligonucleotides with the near-IR flours. A novel synthetic route was developed utilizing a hydrophilic, polyethylene glycol-based (PEG) support with an acid labile Rink Amide linker. The Pcs were functionalized with an amine group for covalent conjugation purposes and were decorated with short PEG chains, serving as solubilizing groups. Mwave-assisted solid-phase synthetic method was successfully applied to obtain pure asymmetrically-substituted mono-amine functionalized Pcs in a short period of time. Three different bioconjugation techniques, reductive amination, amidation and Huisgen cycloaddition, were employed for covalent conjugation of Pcs to oligonucleotides. The described μwave-assisted bioconjugation methods give an opportunity to synthesize and isolate the Pc-oligonucleotide conjugate in a few hours.

Synthesizing and evaluating the photodynamic efficacy of asymmetric heteroleptic A7B type novel lanthanide bis-phthalocyanine complexes

“…In our study, the preparation of A 7 B type rare-earth asymmetric heteroleptic bis-Pc complexes operates interactions between lanthanide (Lu and Eu) mono-Pc complex and a metal-free asymmetric Pc macrocycle in a protic or an aprotic solvent 44 which is a method 4 known as the “raise-by-one-story” method 45 that is mentioned in the introduction part. Starting synthon 4-(6-mercaptohexan-1-ol)phthalonitrile (FN-OH) was synthesized according to literature reports, 46 for production of 4,5-bis(4,7,10-trioxaundecan-1-sulfonyl)phthalonitrile (FN-Pox) simple solvent modifications 47 was done. Metal free phthalocyanines H 2 PcAB 3 OH and H 2 PcPox were obtained by cyclic tetramerization of the phthalonitrile (FN-Pox and FN-OH) in refluxing solvent.…”

Near-Infrared Dyes and Their Use in Medical Science

“…Because of recent advances in the field, the efficiency of these assays has to be amplified. In recent years, when minimal background fluorescence and low scattering in the 650-850 nm region of the electromagnetic spectrum ( Figure 1) were coupled with photophysically and chemically improved fluorophores, near-infrared (NIR) dye-based fluorescence imaging gained importance (1,2). Although the primary purpose of the NIR dyes is aiding imaging, some of the NIR dyes are also used as therapeutic agents for photodynamic therapy (PDT) of cancer and other diseases.…”

“…For most of the applications, it is a "must" to have Pcs with high water solubility along with a functional group that can be used for bioconjugation. However, difficulties in their synthesis limit their usage; therefore, a new synthetic method has been developed by Erdem et al (1,2) that has been published in two different articles in 2008 and 2009 in the Journal of Organic Chemistry Article (1,2). In these studies, using a new solid phase synthesis method, Erdem et al (2) were able to synthesize monoamine and mono-hydroxyl functionalized highly water-soluble Pcs to be used as NIR imaging agents.…”

Design of Turn‐On Near‐Infrared Fluorescent Probes for Highly Sensitive and Selective Monitoring of Biopolymers

“…We utilized a previously developed solid-phase synthesis to accomplish this preparation. [24] First, we prepared amine-functionalized polymer resin by deprotecting Fmoc-protected Rink amide resin. It was then coupled with protected lysine 4, followed by removal of the Fmoc protecting group and subsequent coupling with benzoic-acid-functionalized phthalonitrile 5 to form a resinbound phthalonitrile precursor 6.…”