Functionalized Pt(II) and Ir(III) NIR Emitters and Their Covalent Conjugates with Polymer-Based Nanocarriers

Abstract

Two NIR-emitting platinum [Pt­(N^N^C)­(phosphine)] and iridium [Ir­(N^C)­2­(N^N)]+ complexes containing reactive succinimide groups were synthesized and characterized with spectroscopic methods (N^N^C, 1-phenyl-3-(pyridin-2-yl)­benzo­[4,5]­imidazo­[1,2-a]­pyrazine, N^C, 6-(2-benzothienyl)­phenanthridine, phosphine-3-(diphenylphosphaneyl)­propanoic acid N-hydroxysuccinimide ether, and N^N, 4-oxo-4-((1-(pyridin-2-yl)-1H-1,2,3-triazol-4-yl)­methoxy)­butanoic acid N-hydroxysuccinimide ether). Their photophysics were carefully studied and analyzed using time-dependent density functional theory calculations. These complexes were used to prepare luminescent micro- and nanoparticles with the “core–shell” morphology, where the core consisted of biodegradable polymers of different hydrophobicity, namely, poly­(d,l-lactic acid), poly­(ε-caprolactone), and poly­(ω-pentadecalactone), whereas the shell was formed by covalent conjugation with poly­(l-lysine) covalently labeled with the platinum and iridium emitters. The surface of the species was further modified with heparin to reverse their charge from positive to negative values. The microparticles’ size determined with dynamic laser scanning varies considerably from 720 to 1480 nm, but the nanoparticles’ diameter falls in a rather narrow range, 210–230 nm. The species with a poly­(l-lysine) shell display a high positive (>30 mV) zeta-potential that makes them essentially stable in aqueous media. Inversion of the surface charge to a negative value with the heparin cover did not deteriorate the species’ stability. The iridium- and platinum-containing particles displayed emissions the spectral patterns of which were essentially similar to those of unconjugated complexes, which indicate retention of the chromophore nature upon binding to the polymer and further immobilization onto polyester micro- and nanoparticles for drug delivery. The obtained particles were tested to determine their ability to penetrate into different cells types: cancer cells, stem cells, and fibroblasts. It was found that all types of particles could effectively penetrate into all cells types under investigation. Nanoparticles were shown to penetrate into the cells more effectively than microparticles. However, positively charged nanoparticles covered with poly­(l-lysine) seem to interact with negatively charged proteins in the medium and enter the inner part of the cells less effectively than nanoparticles covered with poly­(l-lysine)/heparin. In the case of microparticles, the species with positive zeta-potentials were more readily up-taken by the cells than those with negative values.

Photosensitive Poly-l-lysine/Heparin Interpolyelectrolyte Complexes for Delivery of Genetic Drugs

“…One can observe that the particles are quite effectively captured by the cells during first hour of co-incubation and the internalization process reaches the plateau within about 2 h. Interestingly, we have observed quite intensive cellular penetration of particulate formulations, which possess negative ζ-potential. However, this is in line with our recent results on cellular internalization of PLL and Hep covering poly(lactic acid)-based nanoparticles [46].…”

Unusual Reactivity and Photophysical Properties of Platinum(II) Pincer Complexes Containing 6,6'‐Diphenyl‐2,2'‐bipyridine Ligands

“…Substitution of chloride in the [Pt(NNC–R)Cl] complexes for various two electron donor ligands is a common reactivity pattern for this type of compounds. [ 8,16,31–38 ] We also planned to obtain the phosphine substituted derivatives of 1–3 under typical reaction conditions shown in Scheme 4 (path I), which consist in mixing of the starting chloride compounds with the phosphine under argon atmosphere. [ 24,39–41 ]…”

“…Substitution of chloride in the [Pt(NNC-R)Cl] complexes for various two electron donor ligands is a common reactivity pattern for this type of compounds. [8,16,[31][32][33][34][35][36][37][38] We also planned to obtain the phosphine substituted derivatives of 1-3 under typical re-action conditions shown in Scheme 4 (path I), which consist in mixing of the starting chloride compounds with the phosphine under argon atmosphere. [24,[39][40][41] To prevent incomplete conversion and speed up the reaction we used a slight excess of triphenylphosphine (1.2 equivalents) that also took into account possible oxidation of the phosphine ligand.…”

“…The reaction shown in Scheme 2 proved to proceed through uncommon pathway and afforded an extremely unusual structural pattern where the chloride keeps bonding to platinum, two phosphine ligands have entered the coordination sphere, whereas in contrast to well-known examples of the substitution chemistry in the pincer [Pt(NNC)Hal] complexes [8,16,[31][32][33][34][35][36][37][38][39][40][41] the NNC ligand is coordinated in terminal manner to form metalating bond with one of the pyridyl rings. To the best of our knowledge this is the first example of the chemistry of the {Pt(NNC)} complexes where the pincer coordination mode is completely broken to form a new metalating bond with an aromatic pyridine ring of the intact NNC ligand.…”

Polymer Particles Bearing Recombinant LEL CD81 as Trapping Systems for Hepatitis C Virus

“…The specific surface area of nano- and microparticles as well as the number of protein molecules per nanoparticle was calculated as described in the Electronic Supporting Information to the article published by Kritchenkov et al [ 29 ]. A brief description of theoretical calculations used in this work is given in Supplementary Materials .…”