From dyes to drugs: The historical impact and future potential of dyes in drug discovery.

In the late 19th century, progress in dye chemistry led to advances in industrial organic chemistry in Germany. Over the next few decades, this revealed dyes not just as color agents but as promising lead compounds for drug development. Collaborations between dye chemists and medical researchers were crucial in turning these unexpected discoveries into structured medicinal chemistry efforts. The outcomes included major drug classes like sulfa antibiotics, antifungal azoles, and others, resulting in a legacy where dyes served not only as biological stains but as crucial tools for understanding complex natural products and drug interactions. Today, the impact of dye molecules persists in clinical therapies, molecular probing, pharmacokinetic tracing, and high-throughput screening. This review underscores the historical contributions shaping contemporary pharmaceutical sciences, highlighting the role of dyes as indispensable tools propelling drug discovery across generations.

Synthetic dyes: A mass spectrometry approach and applications.

Synthetic dyes are found in a wide variety of applications today, including but not limited to textiles, foods, and medicine. The analysis of these molecules is pertinent to several fields such as forensics, environmental monitoring, and quality control, all of which require the sensitivity and selectivity of analysis provided by mass spectrometry (MS). Recently, there has been an increase in the implementation of MS evaluation of synthetic dyes by various methods, with the majority of research thus far falling under electrospray ionization and moving toward direct ionization methods. This review covers an overview of the chemistry of synthetic dyes needed for the understanding of MS sample preparation and spectral results, current fields of application, ionization methods, and fragmentation trends and works that have been reported in recent years.

A mutant R70V/E166A of short manganese peroxidase showing Mn2+-independent dye decolorization.

Il-MnP1, a short-type manganese peroxidase from Irpex lacteus F17, can oxidize some substrates in the absence of Mn2+, but the catalysis was much lower than in the presence of Mn2+. Here, we report a mutant R70V/E166A of Il-MnP1 with some unique properties, which possessed clearly higher catalysis for the decolorization of anthraquinone and azo dyes in the absence of Mn2+ than that of Il-MnP1. Importantly, the optimum pH of R70V/E166A for decolorization of anthraquinone dyes (Reactive Blue 19, RB19) was 6.5, and the mutant achieved high decolorization activities in the range of pH 4.0-7.0, whereas Il-MnP1 only showed decolorization for RB19 at pH 3.5-4.0. In addition, the optimum H2O2 concentration of R70V/E166A for RB19 decolorization was eight times that of Il-MnP1 and the H2O2 stability has improved 1.4 times compared with Il-MnP1. Furthermore, Mn2+ competitively inhibited the oxidation of RB19 by R70V/E166A, explaining the higher catalytic activity of the mutant R70V/E166A in the absence of Mn2+. Molecular docking results suggested that RB19 binds to the distal side of the heme plane in mutant R70V/E166A, which extended from the heme δ-side to the heme γ-side, and close to the mutated residues of R70V and E166A, whereas RB19 could not access the heme pocket of Il-MnP1 due to the steric hindrance of the side-chain group of Arg 70. Thus, this study constructed a useful mutant R70V/E166A and analyzed its higher Mn2+-independent activity, which is very important for better understanding the Mn2+-independent catalytic mechanism for short manganese peroxidases. KEY POINTS: • The mutant R70V/E166A of atypical MnP1 of I. lacteus F17 shows unique catalytic properties. • At pH 6.5, the R70V/E166A had a strong ability to decolorize anthraquinone dyes in the absence of Mn2+. • The binding sites of Reactive Blue 19 in mutant R70V/E166A were elucidated.

Selective Voltammetric Sensor for the Simultaneous Quantification of Tartrazine and Brilliant Blue FCF.

Tartrazine and brilliant blue FCF are synthetic dyes used in the food, cosmetic and pharmaceutical industries. The individual and/or simultaneous control of their concentrations is required due to dose-dependent negative health effects. Therefore, the paper presents experimental results related to the development of a sensing platform for the electrochemical detection of tartrazine and brilliant blue FCF based on a glassy carbon electrode (GCE) modified with MnO2 nanorods, using anodic differential pulse voltammetry. Homogeneous and stable suspensions of MnO2 nanorods have been obtained involving cetylpyridinium bromide solution as a cationic surfactant. The MnO2 nanorods-modified electrode showed a 7.9-fold increase in the electroactive surface area and a 72-fold decrease in the electron transfer resistance. The developed sensor allowed the simultaneous quantification of dyes for two linear domains: in the ranges of 0.10-2.5 and 2.5-15 µM for tartrazine and 0.25-2.5 and 2.5-15 µM for brilliant blue FCF with detection limits of 43 and 41 nM, respectively. High selectivity of the sensor response in the presence of typical interference agents (inorganic ions, saccharides, ascorbic and sorbic acids), other food dyes (riboflavin, indigo carmine, and sunset yellow), and vanillin has been achieved. The sensor has been tested by analyzing soft and isotonic sports drinks and the determined concentrations were close to those obtained involving the chromatography technique.

Steric and Energetic Studies on the Synergetic Enhancement Effect of Integrated Polyaniline on the Adsorption Properties of Toxic Basic and Acidic Dyes by Polyaniline/Zeolite-A Composite.

The synergetic enhancement effect of the polyaniline (PANI) integration process on the adsorption properties of the PANI/zeolite-A composite (PANI/ZA) as an adsorbent for malachite green and Congo red synthetic dyes was evaluated based on classic equilibrium modelling in addition to the steric and energetic parameters of advanced isotherm studies. The PANI/ZA composite displays enhanced adsorption capacities for both methylene blue (270.9 mg/g) and Congo red (235.5 mg/g) as compared to ZA particles (methylene blue (179.6 mg/g) and Congo red (140.3 mg/g)). The reported enhancement was illustrated based on the steric parameters of active site density (Nm) and the number of adsorbed dyes per active site (n). The integration of PANI strongly induced the quantities of the existing active sites that have enhanced affinities towards both methylene blue (109.2 mg/g) and Congo red (92.9 mg/g) as compared to the present sites on the surface of ZA. Every site on the surface of PANI/ZA can adsorb about four methylene blue molecules and five Congo red molecules, signifying the vertical orientation of their adsorbed ions and their uptake by multi-molecular mechanisms. The energetic investigation of the methylene blue (-10.26 to -16.8 kJ/mol) and Congo red (-9.38 to -16.49 kJ/mol) adsorption reactions by PANI/ZA suggested the operation of physical mechanisms during their uptake by PANI/ZA. These mechanisms might involve van der Waals forces, dipole bonding forces, and hydrogen bonding (<30 kJ/mol). The evaluated thermodynamic functions, including enthalpy, internal energy, and entropy, validate the exothermic and spontaneous behaviours of the methylene blue and Congo red uptake processes by PANI/ZA.

Inside the History of Italian Coloring Industries: An Investigation of ACNA Dyes through a Novel Analytical Protocol for Synthetic Dye Extraction and Characterization.

The introduction of synthetic dyes completely changed the industrial production and use of colorants for art materials. From the synthesis of the first synthetic dye, mauveine, in 1856 until today, artists have enjoyed a wider range of colors and selection of chemical properties than was ever available before. However, the introduction of synthetic dyes introduced a wider variety and increased the complexity of the chemical structures of marketed dyes. This work looks towards the analysis of synthetically dyed objects in heritage collections, applying an extraction protocol based on the use of ammonia, which is considered favorable for natural anthraquinone dyes but has never before been applied to acid synthetic dyes. This work also presents an innovative cleanup step based on the use of an ion pair dispersive liquid-liquid microextraction for the purification and preconcentration of historical synthetic dyes before analysis. This approach was adapted from food science analysis and is applied to synthetic dyes in heritage science for the first time in this paper. The results showed adequate recovery of analytes and allowed for the ammonia-based extraction method to be applied successfully to 15 samples of suspected azo dyes from the Azienda Coloranti Nazionali e Affini (ACNA) synthetic dye collection, identified through untargeted HPLC-HRMS analyses.

Cobalt-ferrite/Ag-fMWCNT hybrid nanocomposite catalyst for efficient degradation of synthetic organic dyes via peroxymonosulfate activation.

The activation of peroxymonosulfate (PMS) by nanocatalysts has shown promise as an effective wastewater treatment protocol. Magnetic CoFe2O4/Ag-nanoparticles (NPs) anchored on functionalized multiwalled carbon nanotubes (fMWCNTs), a support material, were synthesized using a one-pot solvothermal method. The surface morphologies and physicochemical properties of the CoFe2O4/Ag-fMWCNT hybrid nanocomposite catalyst were investigated by powder X-ray diffraction analysis, field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and nitrogen adsorption-desorption isotherms. The activity of the nanocomposite combined with PMS (serving as an activator) toward the degradation of rhodamine B, methylene blue, methyl orange, and methyl red was investigated. The obtained optimal 0.02 g CoFe2O4/Ag-fMWCNTs exhibited the highest PMS activation performance, with a removal percentage of 100% for 20 ppm dye concentration at pH 6.5 within 14 min. In addition, the rhodamine B degradation product was investigated by analyzing the intermediate products by liquid chromatography/mass spectrometry (LC-MS). The homogeneous distribution of CoFe2O4/Ag NPs on fMWCNTs accelerated PMS activation and enhanced the catalytic degradation of dyes. The effects of the reaction parameters on the dye degradation efficiency were investigated by using different nanocatalysts (fMWCNTs, CoFe2O4/fMWCNTs, and CoFe2O4/Ag-fMWCNTs) as well as by varying the pH (3-11), dye concentration (10-50 mg/l), catalyst dose (0.002-0.3 g), and PMS dose (0.02-0.1 g). Quenching experiments revealed that sulfate radicals are primarily responsible for rhodamine B degradation. A plausible mechanism for catalytic PMS activation was also proposed. Complete decolorization occurred within the first few minutes of the reaction. Furthermore, the catalytic activity of the CoFe2O4/Ag-fMWCNT/PMS hybrid nanocomposite remained stable after five successive cycles. This study verifies the applicability of CoFe2O4/Ag-fMWCNTs as an ultrafast catalyst for the complete removal of persistent organic pollutants via PMS activation, revealing their promising application in wastewater treatment.

Melanins from the Lichens Lobaria pulmonaria and Lobaria retigera as Eco-Friendly Adsorbents of Synthetic Dyes.

Synthetic dyes are widely used in the industry; they are chemically stable, difficult to neutralize, and therefore they are a threat to the environment when released into wastewaters. The dyes have a significant impact on plant performance by impairing photosynthesis, inhibiting growth, and entering the food chain and may finally result in the toxicity, mutagenicity and carcinogenicity of food products. Implementation of the dark piment melanin for the adsorption of the synthetic dyes is a new ecologically friendly approach for bioremediation. The aim of the present work was to study the physico-chemical characteristics of melanins from the lichens Lobaria pulmonaria and Lobaria retigera, analyze their adsorption/desorption capacities towards synthetic dyes, and assess the capacity of melanins to mitigate toxicity of the dyes for a common soil bacterium Bacillus subtilis. Unique chelating properties of melanins determine the perspectives of the use of these high molecular weight polymers for detoxification of xenobiotics.

Production of fungal laccase on pineapple waste and application in detoxification of malachite green.

The main purpose of this work was to use pineapple crowns as substrate for optimizing laccase production by Trametes versicolor in lab-scale experiments. One-factor-at-the-time analysis and response surface methodology were used to optimize production. A single laccase with molecular weight of 45 kDa was the main protein produced. A maximal laccase activity of 60.73 ± 1.01 U/g was obtained in 7-day cultures, representing a 6.7-fold increase compared to non-optimized conditions. The optimized conditions were temperature: 28 °C; initial moisture: 90%; glucose: 8.38%; yeast extract: 2.86%. Combining activity and stability, the best conditions for using this laccase during the long periods required by large-scale processes are pH 4.0-5.0 and temperature of 40-50 °C. Under these conditions, the crude laccase was efficient in detoxifying the dye malachite green with a KM of 14.33 ± 1.94 µM and a Vmax of 0.482 ± 0.029 µM/min with 0.1 units/mL. It can be concluded that pineapple crown leaves can be effectively used as substrate by T. versicolor for producing laccase under solid-state culture conditions. Laccase is an industrially relevant enzyme and its production with concomitant valorization of pineapple crowns as substrate offers highly interesting perspectives.

Dynamics and thermodynamics for competitive adsorptive removal of methylene blue and rhodamine B from binary aqueous solution onto durian rind.

Concurrent adsorptive removal of methylene blue (MB) and rhodamine B (RhB) onto durian rind (DR) agricultural waste, from an aqueous binary solution as a model of wastewater containing multiple synthetic dyes, was investigated. The concurrent adsorption of the dyes followed pseudo-second-order kinetics. The adsorption isotherm was well simulated by the Langmuir model, implying a monolayer adsorption to the surface with a homogeneous binding energy. The adsorption process was governed by external mass transfer through two-step intraparticle diffusion of the dyes onto the adsorbent surface. The adsorption efficiency of MB (96.4%) is much higher than that of RhB (56.3%). This is attributed to the higher rate constant for the adsorption of MB (0.348 g mg-1 min-1) as compared to that of RhB (0.151 g mg-1 min-1). The adsorption behavior suggested that the two cationic dyes in the binary solution diffused and adsorbed independently and randomly onto the DR surface. The adsorption capacity of MB and RhB in the binary solution (47.4 mg g-1 and 32.9 mg g-1, respectively) is lower than those of their single solute solutions (93.3 mg g-1 and 62.8 mg g-1, respectively), suggesting a competitive effect in their concurrent adsorption. This was confirmed based on the adsorption characteristics of the binary solution with different molar ratios. The competitive effect was attributed to either non-interactive or repulsive electrostatic interactions between the positively charged dyes in the binary system. The domination of MB is attributed to its smaller molecular size, higher planarity, and faster adsorption kinetics compared with RhB.

Invasive plants as biosorbents for environmental remediation: a review.

Water contamination is an environmental burden for the next generations, calling for advanced methods such as adsorption to remove pollutants. For instance, unwanted biowaste and invasive plants can be converted into biosorbents for environmental remediation. This would partly solve the negative effects of invasive plants, estimated at 120 billion dollars in the USA. Here we review the distribution, impact, and use of invasive plants for water treatment, with emphasis on the preparation of biosorbents and removal of pollutants such as cadmium, lead, copper, zinc, nickel, mercury, chromate, synthetic dyes, and fossil fuels. Those biosorbents can remove 90-99% heavy metals from aqueous solutions. High adsorption capacities of 476.190 mg/g for synthetic dyes and 211 g/g for diesel oils have been observed. We also discuss the regeneration of these biosorbents.

Advances in Synthetic Fluorescent Probe Labeling for Live-Cell Imaging in Plants.

Fluorescent probes are powerful tools for visualizing cellular and subcellular structures, their dynamics and cellular molecules in living cells and enable us to monitor cellular processes in a spatiotemporal manner within complex and crowded systems. In addition to popular fluorescent proteins, a wide variety of small-molecule dyes have been synthesized through close association with the interdisciplinary field of chemistry and biology, ranging from those suitable for labeling cellular compartments such as organelles to those for labeling intracellular biochemical and biophysical processes and signaling. In recent years, self-labeling technologies including the SNAP-tag system have allowed us to attach these dyes to cellular domains or specific proteins and are beginning to be employed in plant studies. In this mini review, we will discuss the current range of synthetic fluorescent probes that have been exploited for live-cell imaging and the recent advances in the application that enable genetical tagging of synthetic probes in plant research.

Characterization of synthetic dyes for environmental and forensic assessments: A chromatography and mass spectrometry approach.

Dyes have become common substances since they are employed in mostly all objects surrounding our daily activities such as clothing and upholstery. Based on the usage and disposal of these objects, the transfer of the dyes to other media such as soil and water increases their prevalence in our environment. However, this prevalence could help to solve crimes and pollution problems if detection techniques are proper. For that reason, the detection and characterization of dyes in complex matrices is important to determine the possible events leading to their deposition (natural degradation, attempts of removal, possible match with evidence, among others). Currently, there are several chromatographic and mass spectrometric approaches used for the identification of these organic molecules and their derivatives with high specificity and accuracy. This review presents current chromatographic and mass spectrometric methods that are used for the detection and characterization of disperse, acid, basic, and reactive dyes, and their derivatives.

Synergistic effect in concurrent removal of toxic methylene blue and acid red-1 dyes from aqueous solution by durian rind: kinetics, isotherm, thermodynamics, and mechanism.

In the present study, a synergistic effect between cationic methylene blue (MB) and anionic acid red 1 (AR1) on their concurrent adsorptive removal from aqueous binary solution onto durian rind (DR) was systematically investigated in batch mode across different parameters. The concurrent adsorption was pseudo-second-order kinetics and followed the Langmuir isotherm model, similar to their respective single component. The kinetics and intraparticle diffusion analyses demonstrated that the adsorption rate of MB was a 15-fold faster than AR1, and mass transports were governed by a combination of intraparticle and film diffusion. The synergistic effect was evidenced by an enhanced adsorption efficiency of AR1 from 27 to 42%, while that of MB was almost unchanged (97-98%). By changing the molar ratios of MB and AR1, it was found that the maximum adsorption capacity of MB and AR1 was 249 and 200 mg g-1, respectively, in the binary system higher compared with those in their respective single system (108 and 16 mg g-1). Overall data indicated that the synergistic effect was due to electrostatic interactions between cationic and anionic synthetic dyes, supported by negatively charged DR surface, leading to the formation of their stacking layers on the adsorbent surface. Novelty statement: A synergistic effect in concurrent adsorptive removal of synthetic dyes from multicomponent wastewater remains a critical research challenge. We believed that electrostatic interaction between ionic dyes could be explored to enhance their removal efficiency. This report is the first time that such a synergistic effect between cationic methylene blue (MB) and anionic acid red 1 (AR1) on their concurrent adsorption from aqueous binary system is systematically investigated. The kinetics, isotherm, thermodynamics, and mechanism of the concurrent adsorption of MB and AR1 attributed to the synergistic effect are elucidated in detail.

Enzyme-assisted bioremediation approach for synthetic dyes and polycyclic aromatic hydrocarbons degradation.

Environmental protection from emerging pollutants has become a significant challenge for mankind as an increasing number of contaminants, including synthetic dyes and polycyclic aromatic hydrocarbons (PAHs), represent a serious risk to ecological and environmental balance. Most synthetic dyes have complex aromatic structures and are resistant to degrade by classical approaches, such as physical and chemical processes, including adsorption, chemical coagulation, flocculation, ion exchange, membrane separation, froth flotation, and reverse osmosis. Enzymes-assisted catalytic transformation of pollutants has become a potential alternative to classical methods because of their ability to react with complex compounds, a quick degradation rate, and producing less harmful by-products. Plant peroxidases, and microbial laccase and lignin-degrading peroxidases (manganese and lignin peroxidase) have gained significant attention for treating aromatic waste due to their capability of oxidizing and detoxifying a wide range of recalcitrant xenobiotics, including PAHs and synthetic dyes. Peroxidases being efficient biocatalysts detoxify an array of toxic compounds by simple free-radical mechanism resulting in the formation of oxidized and depolymerized products of significantly reduced toxicity. Moreover, it is an ecofriendly and economically favorable approach towards the biodegradation of recalcitrant and toxic industrial waste. Among microbial and plant peroxidases, bacterial enzymes have broad substrate specificity and can transform a wide range of recalcitrant substrates. Ligninolytic enzymes oxidize the aromatic ring into quinones and acids by producing free hydroxyl radicals instead of dihydrodiols and mineralize aromatic hydrocarbon in combination with cytochrome P450, monooxygenases, and epoxide hydrolases. In the review, an attempt has been made to provide detailed knowledge about the availability of inexpensive peroxidases sources, their mechanism of action, and degradation potential. The present review summarizes the exploitation of peroxidases from plants, bacteria, and fungus (manganese peroxidase, lignin peroxidase, and laccases) for detoxification and degradation of textile dyes as well as PAHs. Conclusively, peroxidases have great potential to react with almost all classes of synthetic dyes and most PAHs due to broad substrate specificity and transformed them into less harmful metabolites.

Factors Affecting Synthetic Dye Adsorption; Desorption Studies: A Review of Results from the Last Five Years (2017-2021).

The primary, most obvious parameter indicating water quality is the color of the water. Not only can it be aesthetically disturbing, but it can also be an indicator of contamination. Clean, high-quality water is a valuable, essential asset. Of the available technologies for removing dyes, adsorption is the most used method due to its ease of use, cost-effectiveness, and high efficiency. The adsorption process is influenced by several parameters, which are the basis of all laboratories researching the optimum conditions. The main objective of this review is to provide up-to-date information on the most studied influencing factors. The effects of initial dye concentration, pH, adsorbent dosage, particle size and temperature are illustrated through examples from the last five years (2017-2021) of research. Moreover, general trends are drawn based on these findings. The removal time ranged from 5 min to 36 h (E = 100% was achieved within 5-60 min). In addition, nearly 80% efficiency can be achieved with just 0.05 g of adsorbent. It is important to reduce adsorbent particle size (with Φ decrease E = 8-99%). Among the dyes analyzed in this paper, Methylene Blue, Congo Red, Malachite Green, Crystal Violet were the most frequently studied. Our conclusions are based on previously published literature.

Application of Molecularly Imprinted Polymers in the Analysis of Waters and Wastewaters.

The increase of the global population and shortage of renewable water resources urges the development of possible remedies to improve the quality and reusability of waste and contaminated water supplies. Different water pollutants, such as heavy metals, dyes, pesticides, endocrine disrupting compounds (EDCs), and pharmaceuticals, are produced through continuous technical and industrial developments that are emerging with the increasing population. Molecularly imprinted polymers (MIPs) represent a class of synthetic receptors that can be produced from different types of polymerization reactions between a target template and functional monomer(s), having functional groups specifically interacting with the template; such interactions can be tailored according to the purpose of designing the polymer and based on the nature of the target compounds. The removal of the template using suitable knocking out agents renders a recognition cavity that can specifically rebind to the target template which is the main mechanism of the applicability of MIPs in electrochemical sensors and as solid phase extraction sorbents. MIPs have unique properties in terms of stability, selectivity, and resistance to acids and bases besides being of low cost and simple to prepare; thus, they are excellent materials to be used for water analysis. The current review represents the different applications of MIPs in the past five years for the detection of different classes of water and wastewater contaminants and possible approaches for future applications.

Microchip isotachophoresis coupled to surface-enhanced Raman spectroscopy for pharmaceutical analysis.

A novel online coupling of microchip isotachophoresis (µITP) with surface-enhanced Raman spectroscopy (SERS) for the analysis of complex samples is presented. Polymeric microchip with coupled channels was used for µITP-SERS analysis of four structurally similar Raman active synthetic dyes (brilliant black BN, carmoisine, ponceau 4R, and sunset yellow FCF) in pharmaceuticals. The µITP separation and simultaneous pre-concentration of the analytes were performed in the first channel of the microchip at pH 6.0 with the aid of non-Raman active discrete spacers (acetate, butyrate, glutarate, pantothenate, and valerate). Silver nanoparticles used for Raman enhancement were present in the second channel, and individual SERS spectra of the dyes were acquired by a mini Raman spectrometer operating at 532 nm. The analytical enhancement factors for silver nanoparticles were 1-5 × 104. The microchip with coupled channels enabled independent µITP separation and SERS detection, and eliminated any adverse impact of nanoparticles on the separation. The developed approach allowed reliable online SERS identification and detection of dyes with limits of detection ranging from 12 to 62 nM. Synthetic dyes were successfully separated, identified, and quantified in pharmaceutical preparations within 7 min without the need for complex or time-consuming sample pretreatment. The results were in good agreement with those obtained by an independent analytical method reported for studied dyes. Graphical abstract.

An Aromatic Dyad Motif in Dye Decolourising Peroxidases Has Implications for Free Radical Formation and Catalysis.

Dye decolouring peroxidases (DyPs) are the most recent class of heme peroxidase to be discovered. On reacting with H2 O2 , DyPs form a high-valent iron(IV)-oxo species and a porphyrin radical (Compound I) followed by stepwise oxidation of an organic substrate. In the absence of substrate, the ferryl species decays to form transient protein-bound radicals on redox active amino acids. Identification of radical sites in DyPs has implications for their oxidative mechanism with substrate. Using a DyP from Streptomyces lividans, referred to as DtpA, which displays low reactivity towards synthetic dyes, activation with H2 O2 was explored. A Compound I EPR spectrum was detected, which in the absence of substrate decays to a protein-bound radical EPR signal. Using a newly developed version of the Tyrosyl Radical Spectra Simulation Algorithm, the radical EPR signal was shown to arise from a pristine tyrosyl radical and not a mixed Trp/Tyr radical that has been widely reported in DyP members exhibiting high activity with synthetic dyes. The radical site was identified as Tyr374, with kinetic studies inferring that although Tyr374 is not on the electron-transfer pathway from the dye RB19, its replacement with a Phe does severely compromise activity with other organic substrates. These findings hint at the possibility that alternative electron-transfer pathways for substrate oxidation are operative within the DyP family. In this context, a role for a highly conserved aromatic dyad motif is discussed.

New photosensitizers for photodynamic therapy.

Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.