Dataset for the Synthesis of Boron-Dipyrrin Dyes, their fluorescent properties, their interaction with proteins, Triton-X-based surfactants, and micellar clusterization approaches to validation based on fluorescent dyes.

The data presented here refer to the research article by Aleksei V. Solomonov, Yuriy S. Marfin, Alexander B. Tesler, Dmitry A. Merkushev, Elizaveta A. Bogatyreva, Elena V. Antina, Evgeniy V. Rumyantsev, and Ulyana Shimanovich "Spanning BODIPY fluorescence with self-assembled micellar clusters", Colloids and Surfaces B: Biointerfaces, 216, 2022, 112532. The present article provides details on optical characterization for a set of meso- and tetra-substituted boron-dipyrrin (BODIPY) complexes encapsulated inside of self-assembled Triton-X-based micellar coordination clusters (MCCs), based on Triton-X family surfactants. Changes in the optical properties of the BODIPY complexes upon interaction with bovine serum albumin, in a binary mixture of THF:H2O and titrated with Triton TX-114, were evaluated. The optical properties and the formation kinetics of the BODIPY-based MCCs and the BODIPY-supported micelle chelator aggregates (MCAs) are presented as well. The presented data provide additional insights into the structural and formation aspects of both the traditional and newly obtained micellar coordination clusters for their future optimization, control, and application. The synthetic procedures for the synthesis of a set of meso- and tetra-substituted BODIPY complexes and their optical properties in different media are also presented. The research is related to the paper (Solomonov et al., 2022).

Spanning BODIPY fluorescence with self-assembled micellar clusters.

BODIPY dyes possess favorable optical properties for a variety of applications including in vivo and in vitro diagnostics. However, their utilization might be limited by their water insolubility and incompatibility with chemical modifications, resulting in low aggregation stability. Here, we outline the route for addressing this issue. We have demonstrated two approaches, based on dye entrapment in micellar coordination clusters (MCCs); this provides a general solution for water solubility as well as aggregation stability of the seven BODIPY derivatives. These derivatives have various bulky aromatic substituents in the 2,3,5,6- and meso-positions and can rotate relative to a dipyrrin core, which also provides molecular rotor properties. The molecular structural features and the presence of aromatic groups allows BODIPY dyes to be used as "supporting molecules", thus promoting micelle-micelle interaction and micellar network stabilization. In the second approach, self-micellization, following BODIPY use, leads to MCC formation without the use of any mediators, including chelators and/or metal ions. In both approaches, BODIPY exhibits an excellent optical response, at a concentration beyond its solubilization limit in aqueous media and without undesired crystallization. The suggested approaches represent systems used to encapsulate BODIPY in a capsule-based surfactant environment, enabling one to track the aggregation of BODIPY; these approaches represent an alternative system to study and apply BODIPY's molecular rotor properties. The stabilized compounds, i.e., the BODIPY-loaded MCCs, provide a unique feature of permeability to hydrophilic ligand-switching proteins such as BSA; they exhibit a bright "turn-on" fluorescence signal within the clusters via macromolecular complexation, thus expanding the possibilities of water-soluble BODIPY-loaded MCCs utilization for functional indicators.

DDAO Controlled Synthesis of Organo-Modified Silica Nanoparticles with Encapsulated Fluorescent Boron Dipyrrins and Study of Their Uptake by Cancerous Cells.

The design of cargo carriers with high biocompatibility, unique morphological characteristics, and capability of strong bonding of fluorescent dye is highly important for the development of a platform for smart imaging and diagnostics. In this paper, BODIPY-doped silica nanoparticles were prepared through a "one-pot" soft-template method using a sol-gel process. Several sol-gel precursors have been used in sol-gel synthesis in the presence of soft-template to obtain the silica-based materials with the most appropriate morphological features for the immobilization of BODIPY molecules. Obtained silica particles have been shown to be non-cytotoxic and can be effectively internalized into the cervical cancer cell line (HeLa). The described method of synthesis allows us to obtain silica-based carriers with an immobilized fluorescent dye that provide the possibility for real-time imaging and detection of these carriers.

Data on peptidyl platform-based anticancer drug synthesis and triton-x-based micellar clusters (MCs) self-assembly peculiarities for enhanced solubilization, encapsulation of hydrophobic compounds and their interaction with HeLa cells.

The data presented here refer to a research article entitled "Self-Assembled Micellar Clusters Based on Triton-X-family Surfactants for Enhanced Solubilization, Encapsulation, Proteins Permeability Control, and Anticancer Drug Delivery" Solomonov et al., 2019. The present article provides the General Procedure for clusterization of Triton-X-based micelles and the effect of (i) metal ion, surfactant, and chelator concentration on the developed clusters formation, (ii) surfactant-chelator relation change, (iii) metal ion-micelles concertation ratio variation, (iv) metal ion replacement, (v) solvent replacement, (vi) kinetics of clusters formation, (vii) hydrophobic fluorescent dye (Coumarin 6) solubilization in aqueous MCs media, (viii) novel anticancer peptidyl drug synthesis and characterization and (ix) the viability of HeLa cells with and without the presence of drug-free Triton-X-based family MCs. These data provide additional insights useful for understanding all aspects of the micellar clusters formation, optimization, and control.

Self-assembled micellar clusters based on Triton-X-family surfactants for enhanced solubilization, encapsulation, proteins permeability control, and anticancer drug delivery.

Non-ionic surfactants have raised a considerable interest for solubilization, encapsulation, permeabilization and controlled release of various compounds due to their unique physicochemical properties. Nevertheless, it is still challenging to create convenient self-assembled multifunctional materials with high solubilization and encapsulation capacities by preserving their advanced capabilities to protect loaded cargos without altering their characteristics. In this work, we present an extended concept of micellar clusters (MCs) formation based on partial entrapment and stabilization of chelate ligands by hydrophobic forces found on the non-ionic surfactant micelle interface of the Triton-X family (TX-100/TX-114), followed by subsequent complexation of the preformed structures either by metal ions or a supporting chelator. The formation aspects, inner structure and the role of external factors such as the addition of competitive ligands have been extensively studied. MCs loaded by hydrophobic fluorescent compounds with high encapsulation efficiency demonstrate an excellent optical response in aqueous media without crystallization as well as sufficient increase in solubility of toxic hydrophobic compounds such as bilirubin (>50 times compared to pure surfactants). Furthermore, Triton-X-based MCs provide a unique feature of selective permeability to hydrophilic ligand-switching proteins such as UnaG and BSA demonstrating bright "turn-on" fluorescence signal either inside the cluster or on its interface via complexation. The proposed strategies allowed us to successfully encapsulate and visualize a newly synthesized, highly hydrophobic anticancer PTR-58-CLB-CAMP peptide drug, while MCs loaded by the drug exhibit a considerable antitumor activity against HeLa cells.

Recent Advances of Individual BODIPY and BODIPY-Based Functional Materials in Medical Diagnostics and Treatment.

BACKGROUND: The group of fluorophores on boron dipyrrin platform (4,4- difluoro-4-bora3a,4a-diaza-s-indacene, also known as BODIPY) has attracted much attention in the field of molecular sensorics, including sensing of biomolecules and bioprocesses. Structural diversity of existing BODIPY with ample opportunities of directed modification of compounds makes this class of fluorophores attractive for medical and biological purposes. The recent progress in the design and functionalization of BODIPY allows using them for modification of drug micro- and nanocarriers in order to improve their therapeutic effect in cancer treatment. At the same time, integration of BODIPY into drug carriers provides the possibility of in vitro and in vivo real time imaging of used drug carriers. The high fluorescent intensity and low toxicity of BODIPY granted for conjugation with different biomolecules. RESULTS: The present review focuses on the recent advances for application of individual BODIPY in medical diagnostics, antimicrobial activity, as well as establishing the role of BODIPY in labeling of biomolecules (e.g. proteins, hormones and DNA). Also the review highlights the potential of BODIPY in functionalization of drug micro- and nanocarriers in order to achieve better therapeutic efficiency compared with non-modified materials. The advantages derived from the use of BODIPY for preparation and modification of drug carriers are critically evaluated and potential for future challenges, especially concerning the design of innovative multi-functional BODIPY-based nanocarriers, is discussed in detail using representative examples from literature. CONCLUSION: Our objective was to show that BODIPY are powerful tools for bioimaging, labeling of biomolecules and construction of new multifunctional drug carriers.

Effect of π-Extended Substituents on Photophysical Properties of BODIPY Dyes in Solutions.

Four boron-dipyrrine (BODIPY) based dyes with π-extended substituents in 8-position of dipyrrin ligand have been synthesized and characterized. Photophysical properties of the obtained compounds have been investigated in different individual solvents. Deposits of solvent polarity and viscosity were evaluated. BODIPY with 8-biphenyl substituent was found to be the fluorescent molecular rotor in contrast to more extended substituents. The complex nature of solvent-solute interactions leads to the poor applicability of standard multiparameter approaches to BODIPY solvatochromic properties. Fluorescence intensity was found to increase in case of solvent polarity growth, it is not typical for BODIPY. Taking that into account the BODIPY with π-extended substituents could be used for fluorescence viscosity measurements, and as the fluorescent media polarity indicators in analytical chemistry and biochemistry.

Analysis of binding ability of two tetramethylpyridylporphyrins to albumin and its complex with bilirubin.

An interaction between 5,10,15,20-tetrakis-(N-methyl-x-pyridyl)porphyrins, x=2; 4 (TMPyPs) with bovine serum albumin (BSA) and its bilirubin (BR) complex was investigated by UV-Viz and fluorescence spectroscopy under imitated physiological conditions involving molecular docking studies. The parameters of forming intermolecular complexes (binding constants, quenching rate constants, quenching sphere radius etc.) were determined. It was showed that the interaction between proteins and TMPyPs occurs via static quenching of protein fluorescence and has predominantly hydrophobic and electrostatic character. It was revealed that obtained complexes are relatively stable, but in the case of TMPyP4 binding with proteins occurs better than TMPyP2. Nevertheless, both TMPyPs have better binding ability with free protein compared to BRBSA at the same time. The influence of TMPyPs on the conformational changes in protein molecules was studied using synchronous fluorescence spectroscopy. It was found that there is no competition of BR with TMPyPs for binging sites on protein molecule and BR displacement does not occur. Molecular docking calculations have showed that TMPyPs can bind with albumin via tryptophan residue in the hydrophilic binding site of protein molecule but it is not one possible interaction way.

Magnetic silica hybrids modified with guanidine containing co-polymers for drug delivery applications.

Guanidine containing co-polymers grafted onto silica nanoparticles to form core-shell structure were prepared by sol-gel method in the presence of γ-Fe2O3 nanoparticles. The morphological features for uncoated and coated silica particles have been characterized with scanning electron microscopy. The results show that the polymer coated silicas exhibit spherical morphology with rough polymeric surface covered by γ-Fe2O3 nanoparticles. The grafting amount of guanidine containing co-polymers evaluated by thermogravimetric analysis was in the range from 17 to 30%. Then, the drug loading properties and cumulative release of silica hybrids modified with guanidine containing co-polymers were evaluated using molsidomine as a model drug. It was shown that after polymer grafting the loading content of molsidomine could reach up to 3.42±0.21 and 2.34±0.14mg/g respectively. The maximum drug release of molsidomine is achieved at pH1.6 (approximately 71-75% release at 37°C), whereas at pH7.4 drug release is lower (50.4-59.6% release at 37°C). These results have an important implication that our magneto-controlled silica hybrids modified with guanidine containing co-polymers are promising as drug carriers with controlled behaviour under influence of magnetic field.

Fluorescent Properties of 8-Substituted BODIPY Dyes: Influence of Solvent Effects.

Three boron-dipyrrine (BODIPY) based dyes with bulky substituents in 8-position of dipyrrin ligand have been synthesized and characterized. Photophysical properties of the obtained compounds have been investigated in different individual solvents and solvent mixtures. Investigated compounds was found to be intensive fluorescent molecular rotors. The influence of different solvent parameters and the substituent nature on rotor characteristics have been observed and discussed. Minor changes in the nature of 8-substituent does not influence the spectral properties, but the presence of nitrogen donor atom in the phenyl substituent could be used for the sensing of the donor-acceptor interactions with solvent or dissolved compounds. The new approach of spectral properties correlation with solvent parameters was proposed, the viscosity parameter should be taken into account in case of BODIPYs with bulky substituents. The intensity of fluorescence molecular rotor properties decrease gradually with the viscosity increase above 1 cP.

Spectroscopic studies of the supramolecular interactions between uracil and 5-hydroxy-6-methyluracil with bovine serum albumin and its bilirubin complex.

Using fluorescence and absorption spectroscopy the interaction of bovine serum albumin and its bilirubin complex with uracil and 5-hydroxy-6-methyluracil in phosphate buffer at pH 7.4 was investigated. The parameters of forming intermolecular complexes (binding constants, quenching rate constants, the radius of the quenching sphere and etc.) were determined. The interaction between serum albumin and uracils is carried out by the static quenching of protein fluorescence and has predominantly hydrophobic character. Using synchronous fluorescence spectroscopy the influence of uracil and 5-hydroxy-6-methyluracil on the conformational changes of the protein molecule was studied. Uracils effectively binds to bilirubin-albumin complex compared to free protein, which is caused by the interaction with tetrapyrrolic pigment in macromolecular complex. Molecular docking calculations also being presented.