Interaction of Fluorescently Substituted Metallacarboranes with Cyclodextrins and Phospholipid Bilayers: Fluorescence and Light Scattering Study

Abstract

We prepared two fluorescein-[3-cobalt(III) bis(1,2-dicarbollide)](-) conjugates. They are sparingly soluble in water and form large aggregates in aqueous solutions. An extensive study on their spectral and aggregation behavior was carried out. To prepare their well-defined dispersion in aqueous systems, we studied the interaction of both probes with two biocompatible amphiphilic systems, cyclodextrins, which are frequently used in drug-delivery systems, and phospholipid membranes, which are the major constituents of cell barriers in living organisms. The presence of fluorescein in both conjugates allows us to study their behavior in detail by steady-state and time-resolved fluorometry, fluorescence correlation spectroscopy, and fluorescence lifetime imaging. The self-assembly of these metallacarboranes in aqueous solutions was studied by dynamic light scattering. The study shows that the compounds interact with cyclodextrins that increases their solubility in water, and they solubilize easily in phospholipid bilayers.

Micelle-like nanoparticles of block copolymer poly(ethylene oxide)-block-poly(methacrylic acid) incorporating fluorescently substituted metallacarboranes designed as HIV protease inhibitor interaction probes

“…225 nm in both samples. Nevertheless, it should be kept in mind that both GB176 and GB179 self-assemble in water and they form aggregates of a similar size [14]. Spectral characteristics of PEO-PMA/GB176 and PEO-PMA/GB179 mixtures are shown in Fig.…”

“…The GB176 and GB179 preparation and characterization have been published elsewhere [14] (structures depicted in Fig. 1).…”

“…From this point of view, the detailed knowledge of the metallacarborane self-assembly is a challenging task [6][7][8][9][10]. Our research covers studies of parent metallacarboranes [11] and (metalla)carborane conjugates [12][13][14] in water to their interaction with surfactants [13], cyclodextrins [14,15], phospholipid membranes [14] and with high-molar-mass hydrophilic polymers [16]. It was recently published that [3-cobalt(III) bis(1,2-dicarbollide)] À interacts with high-molar-mass poly(ethylene oxide), PEO, in aqueous solutions forming an insoluble but stimuli-responsive complex [16].…”

“…Recent data suggest that the chemical structure of the ''nonboron" linker, such as bulkiness, charge, and hydrophobicity can significantly influence both inhibition activity and mechanism [3][4][5]. As the linker, we chose the fluorescein moiety primarily due to its photoluminiscence [14]. Interestingly, its introduction to the structural patterns responsible for the inhibition of HIV protease did not deteriorate the activity substantially [20].…”

“…Details on their synthesis and behavior in aqueous solutions are described in Ref. [14].Here we should point out several features of the probes, which are important when we want to put our study in a broader perspective. The probes represent single (GB176) and double (GB179) cluster compounds designed as HIV protease inhibitors [3][4][5], where the latter seem to be more promising in view of pharmacological applications [3][4][5]20].…”