The development of ruthenium(II) polypyridyl complexes as drug candidates requires understanding the influence of geometry and co-ligands on their chemical reactivity and biological activity. In this work, two chloride complexes of the type [RuIICl(bd)(tpy)]PF6 and [RuIICl(bdq)(tpy)]PF6, where tpy = 2,2':6',2″-terpyridine, bd = o-phenylenediamine and bdq = 3,4-diaminobenzoic acid, were synthesized and characterized. The corresponding aquo complexes, [RuII(OH2)(bd)(tpy)](PF6)2 and [RuII(OH2)(bdq)(tpy)](PF6)2 - were obtained in situ. To understand the kinetics for the spontaneous aquation reaction of the complex chlorides, spectroscopic variation studies in the UV-VIS. region and HPLC were carried out, revealing that [RuIICl(bd)(tpy)]PF6 has a higher rate constant than the complex with bdq ligand in the aquation reaction. The experimental results were complemented by theoretical calculations to determine the aquation kinetic constants as well as the activation parameters. The associative mechanism was proposed for the aquation reaction, with the steric effect of the COOH substituent group influencing the entry of the aquo ligand. In understanding their interaction with biomolecules, spectroscopic studies showed that both complexes interact with fs-DNA by intercalation, with apparent binding constants of (2.4 ± 0.1) × 106 and (1.3 ± 0.3) × 106 L mol-1 for [RuIICl(bd)(tpy)]PF6 and [RuIICl(bdq)(tpy)]PF6, respectively, and DNA cleavage only by [RuIICl(bd)(tpy)]PF6. Both chloride ruthenium(II) complexes not showed decreasing in the MDA-MB-231 viability cells. While, the [RuIICl(bd)(tpy)]PF6, demonstrated interested efficacy in inhibiting Zika and Chikungunya viruses.

Triple-negative breast cancer (TNBC) remains a major therapeutic challenge due to the lack of targeted treatments. In this study, 5,10,15,20-tetrakis(N-ethylpyridinium-3-yl)porphyrin chloride (H2TE-3-PyPCl4, abbreviated as H2P, free-base) and five metalated derivatives with Zn(II), Mn(III), Cu(II), Sn(IV), and Au(III) were synthesized and evaluated for both dark and photo-induced cytotoxicity against MDA-MB-231 TNBC cells. Among these, the Cu(II), Sn(IV), and Au(III) complexes are reported here for the first time. Some of the porphyrins displayed marked phototoxic effects, with IC50 values in the nanomolar range. H2P and ZnP showed the highest phototoxicity at 520 +/- 5 nm, with IC50 values of 0.21 and 0.22 mu M, respectively. The phototoxicity indexes (PI) were also remarkably high, ranging from 40 for AuP to 4,762 for H2P. This is the first report of a tin(IV) porphyrin (SnP) being evaluated against MDA-MB-231 cells. In addition to exhibiting significant phototoxicity (IC50 = 0.77 mu M), SnP completely suppressed the survival of irradiated clonogenic cells, underscoring its potential for developing novel therapeutic approaches for this aggressive cancer type. Overall, these results highlight the potential of water-soluble porphyrins as effective photosensitizers in PDT and support their further investigation as innovative candidates for TNBC treatment.

This innovative study introduces an eco-conscious and cost-effective approach to synthesizing gelatin-based carbon dots (CDs) via two distinctive methods: hydrothermal processing in a muffle furnace (CDs-MF) and domestic microwave (CDs-MW). Both strategies harness natural, low-cost materials and prioritize simplicity, sustainability, and environmental friendliness, culminating in effective fluorescent sensing of the pesticide thiamethoxam (TMX). For the hydrothermal route, the investigation explores two purification approaches—ultracentrifugation (CDs-MF-C) and 0.22 µm syringe filtration (CDs-MF-F)—while the microwave-derived CDs (CDs-MW) undergo dialysis alone. This study aims to investigate how synthesis and purification impact the CDs structural, morphological, and photophysical characteristics. The difference in size was obtained from transmission electron microscopy (TEM): 30–40 nm for CDs-MF-C, 12–15 nm for CDs-MF-F, and 3–6 nm for CDs-MW. Fluorescence emission performance reveals that CDs-MF-F performs a fluorescence quantum yield of 27%, CDs-MF-C at 23%, and CDs-MW at a modest 3%. All variants exhibit TMX detection via fluorescence quenching through the inner filter effect (IFE). Analytically, CDs-MF-C stands out with the lowest detection limit (LOD = 0.396 ppm) and quantification limit (LOQ = 1.317 ppm), followed by CDs-MF-F (LOD = 0.475 ppm; LOQ = 1.585 ppm) and CDs-MW (LOD = 0.549 ppm; LOQ = 1.831 ppm). These findings emphasize the unique interplay between the synthesis pathway, purification strategy, and functional performance, demonstrating the critical importance of tuning structural properties for optimizing carbon-dot sensors.

Designing photosensitizers (PS) with ideal properties for Photodynamic Therapy (PDT) remains challenging, but crucial for advancing PDT as a viable anticancer treatment. Combining porphyrin with potent anticancer agents, such as piperazine and morpholine groups, has the potential to give rise to innovative photosensitizers that exhibit heightened PDT effects in cancer cells. Herein, we present two novel molecules bearing piperazine (PpIXPip) or morpholine (PpIX-Morp) groups conjugated to Protoporphyrin IX (PpIX), describing their photophysical and photodynamic characteristics. Analysis of the photophysical properties revealed similar fluorescence quantum yields and lifetimes between PpIX and the conjugated molecules. The PpIX-Pip showed higher production of singlet oxygen and better interaction with HSA in comparison to PpIX-Morp. Cellular uptake assays revealed a greater incorporation rate for PpIX-Pip (37 %) compared to PpIX-Morp (29 %) in HeLa cells. Essentially, both PpIX derivatives exhibited superior uptake efficiencies compared to PpIX alone (17 %). The descending order of IC50 values was PpIX > PpIX-Morp > PpIX-Pip, indicating that the introduction of piperazine and morpholine groups to PpIX elevated the toxicity in HeLa cells. When comparing IC50 values obtained under irradiation to the dark control, it was observed that PpIX-Pip demonstrated higher phototoxic effect (phototherapeutic index, PI > 5), whereas PpIX-Morp exhibits medium phototoxicity towards HeLa cells (PI > 2). Among the newly studied porphyrins, PpIX-Pip displayed a higher singlet oxygen generation rate, and improved cellular uptake as well as lower value of IC50 in the light. This is the first report highlighting the PDT activity of PpIX modified with the N-methylpiperazine group. Our findings open avenues for the design and development of photosensitizers linked to anticancer agent moieties, encompassing groups like piperazine and morpholine.

Carbonized polymer dots (CPDs) were obtained by using microwave irradiation under the same conditions. However, different carbogenic precursors were used, such as aromatic diamine molecules, ortho-phenylenediamine (o-OPDA), and 3,4-diaminobenzoic acid (3,4-DABA). Both carbon nanoparticles showed different structural results based on Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, and atomic force microscopy analyses. However, there are similar spectroscopic (UV-visible and fluorescence emission) profiles. The photophysical results, like quantum yield (QY) and fluorescence lifetime, were not identical; CPDs-OPDA has a higher QY and fluorescence lifetime than CPDs-3,4-DABA. CPDs-3,4-DABA presents a more hydrophobic character than CPDs-OPDA and has a more negative superficial charge. Cell viability studies in both standard and tumor lines demonstrated higher cytotoxicity from CPDs-OPDA than that from CPDs-3,4-DABA. The oxidative stress identified in cells treated with CPDs-OPDA was based on reactive oxygen species and associated with nitric oxide production. CPDs-3,4-DABA showed more DPHH inhibition than CPDs-OPDA, indicating the antioxidant activity of CPDs.

Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [RuII(L)(NO2)(tpy)]PF6 where tpy = 2,2':6',2”-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [RuII(L)(NO2)(tpy)]+ were evaluated. The Ka values for the HSA–[RuII(bdq)(NO2)(tpy)]+ is 10 times bigger than HSA–[RuII(bd)(NO2)(tpy)]+. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [RuII(bdq)(NO2)(tpy)]+ is found close to the Trp-241 residue, while the [RuII(bd)(NO2)(tpy)]+ complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (Kb) and ethidium bromide replacement (KSV and Kapp) showed weak interaction in the system fs-DNA-[RuII(bdq)(NO)(tpy)]+. Furthermore, fs-DNA–[RuII(bd)(NO2)(tpy)]+ and fs-DNA–[RuII(bd)(NO)(tpy)]3+ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA–[RuII(bd)(NO2)(tpy)]+ and fs-DNA–[RuII(bd)(NO)(tpy)]3+, suggest semi-intercalative accompanied by major groove binding interaction modes. The [RuII(bd)(NO2)(tpy)]+ and [RuII(bd)(NO)(tpy)]3+ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral.

Carbon dots (CDs) exhibit luminescence, biocompatibility, and higher water solubility. This material has been developed for biological applications, specifically in bioimaging. In this work, the gelatin carbon dots (CDg) was obtained from commercial gelatin using a hydrothermal method in domestic microwave, and the suppression fluorescent mechanism were enhanced by the addition of the [RuII(bdq)(NO)(tpy)]3+ (Rubdq-NO+) complex ion. After purification through a dialysis bag, the resulting CDs (CDg) exhibit fluorescent emission at 400 nm and maintained fluorescence stability in an aqueous solution (pH = 7) for 30 days under 5 degrees C. Fluorescence quenching studies revealed an electrostatic interaction between the negative charge from CDg (delta = - 20 mV) and the positively charged nitrosyl (NO+) ligand of the ruthenium complex (Rubdq-NO+), resulting in quenching of the CDg fluorescence due to the inner filter effects (IFE). The chemiluminescence reaction of CDg and Rubdq-NO-CDg in presence of norepinephrine (NOR) were evaluated. NOR in PBS are liable to undergo spontaneous oxidation to quinone form (NOR-quinone). CDg are believed interact with NOR-quinone and an electron transfer occur obtained CDg+ accompanied to green emission fluorescence (520 nm). While for Rubdq-NO-CDg in presence of NOR, the green emission occurs accompanied by NO0 release using DAF-2 probe.

Carbon dots (CDs) are nanometer-scale particles produced from carbon sources that exhibit fluorescence emission. The present work presents the synthesis and characterization of CDs, as well as the sensing studies for the determination of chloramphenicol (CAP). CAP is an antibiotic used in human medicine and agriculture, and its indiscriminate use and inappropriate disposal have caused damage to human health and the environment. The carbonaceous precursor used in the synthesis of CDs was 3,4-diaminobenzoic acid (3,4-DABA) through the hydrothermal method via domestic microwave irradiation. The first synthesis procedure was carried out in the presence of water/ethanol (a-CDs) and the second in the presence of 1 mol/L sodium hydroxide/ethanol (b-CDs). The CDs were initially characterized in terms of spectroscopic properties in the ultraviolet and visible region (UV-visible), Fourier-transform infrared (FTIR) spectra, Raman spectroscopy, and fluorescence emission spectroscopy. Sensing studies for the antibiotic C were performed by fluorescence suppression in the presence of a- and b-CDs, as well as the precursor 3,4-DABA. The a- and b-CDs presented similar values of linear range 0.00080-0.0050 mg/ml and limit of detection (LOD) = 0.00030 mg/ml (0.30 ppm) for CAP. Then, a- and b-CDs were embedded in Whatman and Mellita® filter paper, and CAP sensing was evaluated through UV light excitation.

Nitric oxide (NO) can modify proteins via tyrosine nitration, for example. Thus, this molecule has high cytotoxic potential, which has led to special interest in photochemical processes that release NO. Ruthenium nitrosyl complexes are excellent candidates for exogenous NO delivery. In this context, ruthenium nitrosyl complexes under light irradiation have been explored in different photochemical approaches that involve NO release by different pathways. Several aspects should be considered: reactive nitrogen species (RNS) formation, NO release rate constant, photochemical and photophysical properties of ruthenium nitrosyl complexes, photochemical pathway, and NO photodelivery, among others. This chapter summarizes the main characteristics and applications of light-driven nitrosyl ruthenium complexes.

Ruthenium complexes that act as nitric oxide (NO) donors show potential cytotoxicity in tumor models. In this work, we proposed the synthesis of the new nitrosyl ruthenium complex trans-[Ru(NO2)(NO)(dppb)(o-bdqi)]Cl2, containing a non-innocent ligand of the o-phenylenediamine type (o-bdqi). The 31P{1H} NMR spectra confirmed that the trans-[Ru(NO2)(NO)(dppb)(o-bqdi)] is the isomer formed. The complex was characterized by elemental analysis, mass spectrometry, UV–vis and infrared spectroscopy and cyclic voltammetry. Natural transition orbitals (NTOs) for trans-[RuCl2(dppb)(o-bdqi)] and trans-[Ru(NO2)(NO)(dppb)(o-bdqi)]Cl2 complex were obtained with TD-DFT/B3LYP methodology to contribute to the assignment of electronic transition. A micellar system (F-127/Ru) produced with Pluronic F-127 copolymer was used as a drug delivery system, due to the hydrophobicity of the complex. The F-127/Ru system showed NO release in aqueous media. The free complex showed higher cytotoxicity than the F-127/Ru system in the studied tumor cells. However, the F-127/Ru system showed a higher selectivity index for lung cells. This shows that the Pluronic F-127 carrier can be a good alternative in the use of hydrophobic nitrosyl ruthenium compounds in the treatment of some types of cancer.

Two non-symmetric free-base porphyrins, one with an electron density withdrawing group (-NO2), H-2 (NPTPP), and the other with an electron density donor group (-NH2), H-2 (APTPP), were synthesized, characterized and the photophysical properties reported. The compound H-2 (APTPP) showed a fluorescence quantum yield (Phi(F1) = 0.12) similar to that of H-2 (TPP), and this derivative showed the longer lifetime in the singlet state (tau(1) = 1.51 ns and tau(2) = 7.74 ns; bi-exponential process) and the ability to generate singlet oxygen. It also showed relative resistance to the photobleaching process. However, it presented a high degree of aggregation in a medium that mimicked the biological one. In cell viability tests against B16-F10 cells, H-2 (APTPP) did not show cytotoxic activity either in absence or presence of a light stimulus. H-2 (NPTPP) at 50 mu M showed a reduction in cell viability (of up to 50%) under dark or light conditions. The liposomal formulation containing H-2 (APTPP) was stable for 2 h and caused the death of tumor cells (up to 95%) even in absence of light stimulus, showing that cell death is associated with non-photodynamic processes.

Zinc oxide (ZnO) is a very attractive material which has received growing attention in the academic and technological areas. This metal oxide shows several advantageous properties such as facile and inexpensive synthesis, low toxicity, high surface area, and rich surface chemistry. However, the most impressive property of ZnO is the possibility of obtaining ZnO nanoparticles with different morphologies and crystal size by merely changing the synthetic parameters, such as temperature, pH, or the solvent. Thus, the combination of the attractive chemical, optical, and electrical properties of ZnO to the possibility of easily producing ZnO nanoparticles with different sizes and morphologies makes this metal oxide an extremely versatile material. Because of this versatility, ZnO has found several applications, including the development of electronic and optoelectronic devices, energy conversion in solar cells and supercapacitors, sensing and electrochemical sensing, besides several biomedical applications in photodynamic therapy, disease diagnoses, and microbial killing. Therefore, the objective of this chapter is to highlight the main approaches used to achieve the efficient application of ZnO in biomedical, energy conversion, and electrochemical sensing fields.

The interaction between two nitrosyl ruthenium complexes [Ru (NH.NHq-COOH)(tpy)NO](PF6 )3 (RuBDQ) and [Ru (NH.NHq-H)(tpy)NO](PF6 )3 (RuBD) and human serum albumin (HSA) was investigated using spectroscopic and computational methods. From fluorescence experiments, a dynamic quenching mechanism and binding constants at a single site demonstrated the higher stability of the RuBDQ-HSA system at 308 K compared with RuBD-HSA. Thermodynamic parameters indicated that binding of RuBDQ and RuBD to HSA was mainly driven by hydrophobic interaction and hydrogen bonding, respectively. Synchronous fluorescence and FT-IR results suggested that interactions between both nitrosyl ruthenium complexes and HSA affected protein conformation. Competition experiments revealed that RuBDQ and RuBD bound to Sudlow sites I and II, respectively. Molecular docking results showed that RuBDQ interacted with Ser-192 and Ala-291 residues via hydrogen bonding and polar contact, respectively, whereas RuBD associated with Asn-391 via a polar interaction. Noncovalent interaction results suggested that van der Waals interactions were the main binding forces for both systems, i.e. RuBDQ associated with Trp-214 via van der Waals interaction and with Ty-150 via dipole-dipole bonding, whereas RuBD associated with Tyr-452 via van der Waals forces. The Asp-391 residue interacted with the nitrosyl ligand via polar contact and the terpyridine ligand via van der Waals interaction.

Lapachol is a natural product that has potential biological activity due it is several mechanisms in the cell, including redox cycles involving the generation of free radicals and other reactive oxygen species (ROS). Metal ions can bind to lapachol which may exhibit different oxidation states (quinone, semiquinone and catechol) and this binding ability is important role of quinone in biological system. We proposed the new cobalt (III) and ruthenium (III) complexes of lapachol aiming to investigate the chemical behavior of trivalente metal center and lapachol as well as these metal complexes can influence in the biological properties. The complexes were characterized using several physicochemical techniques such as elementary analysis, mass spectra, spectroscopic behavior in the infrared and UV–visible region, as well as electrochemical process. The complex formed by the reaction between ruthenium(III) and the lapacholate anion was isolated as RuII-quinone and RuIII-semiquinone, which exhibited valence tautomerism. Both compounds presented cytotoxicity against a murine melanoma cell line (B16/F10). However, the [Ru(lap─)2(NH3)2]+ complex exhibited significant cytotoxic effects as a result of superoxide anion production, determined using the NBT assay.

ABSTRACT This work describes the influence of aloe vera gel on Pluronic F127 triblock copolymer (F127) micellization behavior. Aloe vera gel was obtained from aloe vera mucilage found in leaf pulp. F127 (20% w/w) gel and the aloe vera/F127 blend gel were obtained by using the cold method. Fourier transform infrared spectroscopy and X‐ray diffraction analyses of lyophilized samples did not show any important copolymer interaction between aloe vera gel and F127. However, in aqueous medium, the dynamic light scattering data showed that there was an important reduction in micelle size with increasing temperature of the aloe vera/F127 blend hydrogel. The differential scanning calorimetry results indicate that the aloe vera/F127 blend has a higher micellization temperature, affected by the lower dehydrating effect of the poly(propylene oxide) blocks during the micelle formation in comparison to F127 gel. The texture analyses (hardness and adhesiveness) showed that the addition of aloe vera gel did not change the Pluronic F127 gel texture properties. The photosensitizer zinc phthalocyanine (ZnPC) was incorporated into the aloe vera/F127 blend, and the results suggest that this formulation is suitable as a ZnPC delivery system for photodynamic therapy. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135 , 46191.

Candidiasis, a major opportunistic mycosis caused by Candida sp., may comprise life-threatening systemic infections. The incidence of non-albicans species is rising, particularly in South America and they are frequently drug resistant, causing unresponsive cases. Thus, novel antimycotic agents are required. Here we tested the antifungal activity of [RuIII(NH3)4catechol]+ complex (RuCat), approaching possible action mechanisms on fluconazole-resistant Candida tropicalis. RuCat significantly (P < 0.05) inhibited the growth and viability of C. tropicalis dose-dependently (IC50 20.3 μM). Cytotoxicity of RuCat upon murine splenocytes was lower (Selectivity Index = 16). Scanning electron microscopy analysis showed pseudohyphae formation, yeast aggregation and surface damage. RuCat-treated samples investigated by transmission electron microscopy showed melanin granule trafficking to cell surfaces and extracellular milieu. Surface-adherent membrane fragments and extracellular debris were also observed. RuCat treatment produced intense H2DCFDA labeling, indicating reactive oxygen species (ROS) production which caused increased lipoperoxidation. ROS are involved in the fungicidal effect as N-acetyl-L-cysteine completely restored cell viability. Calcofluor White chitin staining suggests that 70 or 140 μM RuCat treatment for 2 h affected cell-wall structure. PI labeling indicated necrotic cell death. The present data indicate that RuCat triggers ROS production, lipoperoxidation and cell surface damage, culminating in selective necrotic death of drug-resistant C. tropicalis.

Ultradeformable liposomes (UDLs) as a drug delivery system (DDS), prepared from the unsaturated phospholipid, dioleylphosphocholine (DOPC), and containing the non-ionic surfactant Tween 20 as edge activator, have been explored as topical vehicles for zinc phthalocyanine (ZnPc) and the nitrosyl ruthenium complex [Ru(NH.NHq)(tpy)NO]3+ (RuNO) as a photosensitizers for co-generation of 1O2 and NO as reactive species, respectively. However, in order to ensure that ZnPc was present in the UDLs in its monomeric form - essential for maximal ZnPc photophysical properties - it was necessary to replace 40wt% of the DOPC with the saturated phospholipid, dimyristoylphosphocholine (DMPC). The resultant ZnPc and complex [Ru(NH.NHq)(tpy)NO]3+ containing UDLs were stable for at least a month when stored at 4°C, six times more elastic/deformable than conventional liposome (c-Ls), i.e. liposome prepared using the same weight ratio of lipids but in the absence of Tween 20, and to significantly enhance the in vitro permeation of ZnPc across fresh pig ear skin. The UDLs DDS incorporating ZnPc and [Ru(NH.NHq)(tpy)NO]3+ were toxic (by the MTT assay) towards B16-F10 melanoma cells when irradiated with visible light at 670nm, the maximum absorption of ZnPc, and at a dose of 3.18J/cm2, but not when applied in the absence of light as expected. Based on these results it is proposed that the novel topical UDLs formulation developed is a suitable delivery vehicle for photodynamic therapy.