The search for novel self-assembled materials has brought particular attention towards functional melanin-like polymers able to form robust underwater adhesive coatings on various substrates. In this scenario, the realization of hybrid porphyrin-melanin like films can gather attention by the well-known photophysical and chemical properties of porphyrinoid systems. Thus, in this paper we aim to synthesize functionalized melanin-like films on glass substrates by using four different cationic porphyrins: H2T4, CuT4, ZnT4 and SnT4. Alongside the porphyrins, we also investigated the effects of adding amine-rich molecules such as spermine on the hierarchical self-assembly of the hybrid melanin-like@glass films. We have set up a simple and feasible synthetic method which consists of dipping the glass substrate in either a PBS buffer solution of porphyrin/L-DOPA or porphyrin/spermine/L-DOPA with an incubation time of 14 days. The obtained functionalized glass substrate was characterized by UV-vis spectroscopy to ensure the deposition of the hybrid porphyrin-melanin film and by AFM to study its surface morphological properties. Our analysis revealed no significant differences in the surface textures of the hybrid film obtained with H2T4 and CuT4, contrary to both the ZnT4 and SnT4 films, which exhibited an increase in all surface parameters on account of their different coordination number. On the other hand, the addition of spermine involved a general flattening of the analyzed surface area in all instances. Overall, our results can be exploited in the ever-growing materials science field to develop tailored and robust functionalized melanin-like films.

The design of functional chiral nanostructures in aqueous solution represents one of the most exciting challenges in supramolecular chemistry, offering potential applications in catalysis, sensing, and materials science. In this scenario, it has already been shown that the hierarchical step-by-step addition of porphyrins to calix[4]arene aqueous solutions yields porphyrin-calixarene supramolecular complexes with exact and tuneable stoichiometries and defined dimensionality. The present study reports the formation of novel 1D porphyrin-calix[4]arene assemblies, achieved through a hierarchical and stoichiometrically controlled self-assembly process in water using host-guest interactions between the anionic trisulfonated porphyrin, H2DPPS3, and the cationic bis-calix[4]arene, BC4. In addition, to obtain chiral 1D noncovalent assemblies, the copper(II) porphyrin, CuDPPS3, and the enantiomerically pure bis-calix[4]arenes, (R,R)- and (S,S)-BC4, were also used in aqueous solution. The stepwise formation of linear noncovalent and chiral assemblies, based on porphyrin-calixarene complexes, was demonstrated by a number of different techniques such as: UV-vis spectroscopy, circular dichroism (CD), resonance light scattering (RLS) and scanning electron microscopy (SEM), revealing precise stoichiometries, sequence, dimensionality and induction of chirality.

Porphyrins are highly conjugated macrocyclic compounds that possess exceptional photophysical and chemical properties, progressively establishing themselves as versatile tools in the structural investigation of biomolecules. This review explores their role as chiroptical conformational probes, focusing on their interactions with DNA and RNA. The planar electron rich structure of porphyrin macrocycle that promote π–π interactions, their easy functionalization at the meso positions, and their capacity to coordinate metal ions enable their use in probing nucleic acid structures with high sensitivity. Emphasis is placed on their induced circular dichroism (ICD) signals in the Soret region, which provide precise diagnostic insights into binding mechanisms and molecular interactions. The review examines the interactions of porphyrins with various DNA structures, including B-, Z-, and A-DNA, single-stranded DNA, and G-quadruplex DNA, as well as less common structures like I-motif and E-motif DNA. The last part highlights recent advancements in the use of porphyrins to probe RNA structures, emphasizing binding behaviors and chiroptical signals observed with RNA G-quadruplexes, as well as the challenges in interpreting ICD signals with other RNA motifs due to their inherent structural complexity.

Chirality plays a fundamental role in natural phenomena, yet its manifestation on solid surfaces remains relatively unexplored. In this study, we investigate the formation of chiroptical melanin-based self-assembled films on quartz substrates, leveraging mussel-inspired surface chemistry. Water-soluble porphyrins serve as molecular synthons, facilitating the spontaneous formation of hetero-aggregates in phosphate-buffered saline containing L- or D-DOPA. Spectroscopic analysis reveals chiral transfer from DOPA enantiomers to porphyrin hetero-aggregates, followed by the disruption of these latter and subsequent generation of chiral melanin structures in solution. Quartz substrates inserted into these solutions spontaneously accumulate homogeneous melanin-like films over days, demonstrating the feasibility of self-assembly. The resulting films exhibit characteristic UV/Vis and CD spectra, with distinct signals indicating successful chiral induction. Interestingly, the AFM characterizations reveal a distinct surface morphology, and in addition, some thermal and mechanical properties have been taken into account. Overall, this study sheds light on the formation, stability, and chiroptical properties of melanin-based films, paving the way for their application in various fields.

By a multi-technique approach, four different porphyrins have been tested as chiroptical probes for mature endogenous micro-RNAs.

Many chronic diseases, including cancer and neurodegeneration, are linked to proteasome dysregulation. Proteasome activity, essential for maintaining proteostasis in a cell, is controlled by the gating mechanism and its underlying conformational transitions. Thus, developing effective methods to detect gate-related specific proteasome conformations could be a significant contribution to rational drug design. Since the structural analysis suggests that gate opening is associated with a decrease in the content of α-helices and β-sheets and an increase in random coil structures, we decided to explore the application of electronic circular dichroism (ECD) in the UV region to monitor the proteasome gating. A comparison of ECD spectra of wild type yeast 20S proteasome (predominantly closed) and an open-gate mutant (α3ΔN) revealed an increased intensity in the ECD band at 220 nm, which suggests increased contents of random coil and β-turn structures. This observation was further supported by evaluating ECD spectra of human 20S treated with low concentration of SDS, known as a gate-opening reagent. Next, to evaluate the power of ECD to probe a ligand-induced gate status, we treated the proteasome with H2T4, a tetracationic porphyrin that we showed previously to induce large-scale protein conformational changes upon binding to h20S. H2T4 caused a significant increase in the ECD band at 220 nm, interpreted as an induced opening of the 20S gate. In parallel, we imaged the gate-harboring alpha ring of the 20S with AFM, a technique that we used previously to visualize the predominantly closed gate in latent human or yeast 20S and the open gate in α3ΔN mutant. The results were convergent with the ECD data and showed a marked decrease in the content of closed-gate conformation in the H2T4-treated h20S. Our findings provide compelling support for the use of ECD measurements to conveniently monitor proteasome conformational changes related to gating phenomena. We predict that the observed association of spectroscopic and structural results will help with efficient design and characterization of exogenous proteasome regulators.

The aggregative state of the Zn(II) tetra-spermine porphyrin derivative, ZnTCPPSpm4, has been investigated in the presence of different buffers at the same pH value: 5K (cacodylate) buffer, phosphate sodium salt buffer, and PBS. The photophysical characterizations (UV-vis, Fluorescence, and RLS) have indicated a precise self-assembly phenomenon depending on the buffered solution used. The porphyrin does not undergo a significant aggregation in 5K buffer, differently from what occurs in phosphate and PBS buffers. Here, the likely specific interaction between the phosphate molecules and spermine pendants leads to spontaneous porphyrin aggregation, as detected by the high fluorescence quenching, enhancement of the RLS signal, and a significant splitting of the porphyrin Soret band. As a result, the current paper aims to highlight the importance of the employed buffer throughout the experimental procedures performed in the presence of porphyrinoids.

Cationic porphyrins exhibit an amazing variety of binding modes and inhibition mechanisms of 20S proteasome. Depending on the spatial distribution of their electrostatic charges, they can occupy different sites on α rings of 20S proteasome by exploiting the structural code responsible for the interaction with regulatory proteins. Indeed, they can act as competitive or allosteric inhibitors by binding at the substrate gate or at the grooves between the α subunits, respectively. Moreover, the substitution of a charged moiety in the peripheral arm with a hydrophobic moiety revealed a “new” 20S functional state with higher substrate affinity and catalytic efficiency. In the present study, we expand our structure–activity relationship (SAR) analysis in order to further explore the potential of this versatile class of 20S modulators. Therefore, we have extended the study to additional macrocyclic compounds, displaying different structural features, comparing their interaction behavior on the 20S proteasome with previously investigated compounds. In particular, in order to evaluate how the introduction of a peptidic chain can affect the affinity and the interacting mechanism of porphyrins, we investigate the MTPyApi, a porphyrin derivatized with an Arg–Pro-rich antimicrobial peptide. Moreover, to unveil the role played by the porphyrin core, this was replaced with a corrole scaffold, a “contracted” version of the tetrapyrrolic ring due to the lack of a methine bridge. The analysis has been undertaken by means of integrated kinetic, Nuclear Magnetic Resonance, and computational studies. Finally, in order to assess a potential pharmacological significance of this type of investigation, a preliminary attempt has been performed to evaluate the biological effect of these molecules on MCF7 breast cancer cells in dark conditions, envisaging that porphyrins may indeed represent a powerful tool for the modulation of cellular proteostasis.

Mussels-inspired melanin coatings from L-DOPA are getting growing attention by virtue of their facile synthesis and low-cost production. However, the spontaneous DOPA-melanin deposition is often affected by numerous experimental factors which hinder the preparation of robust adhesive films for practical application. Hence, we have set up a feasible method to functionalized in an aqueous medium an ordinary glass substrate with a self assembled and homogeneous DOPA-melanin film. The sample was employed to efficiently remove a dye pollutant, the methylene blue, from water. Interestingly, the introduction of the H2TCPPspm4 porphyrin allows obtaining a hybrid film with an enhancement of 20% in terms of adsorption capacity. The hybrid system exhibited significant reusability for more dye-adsorption cycles, suggesting the possibility to actualize a smart, re-usable and easy-to-scale device with high potentiality in water remediation technology.

The self-assembly process appears as a powerful and attractive strategy for constructing complex supramolecules by the spontaneous organization of appropriate building blocks. In this scenario, water-soluble porphyrinoids lend themselves as ideal paradigms to disclose the self-assembly phenomenon by exploiting their well-known tendency to build aggregates in aqueous media via weak non-covalent forces. Nevertheless, the spontaneous organization of achiral porphyrins can result in a final chiral superstructure moving away from single-molecule behaviour to supramolecular chirality. Therefore, over the years numerous attempts have been implemented to investigate how a porphyrin aggregate, made up of achiral monomers, becomes not-symmetric and which processes govern the bias for a certain enantiomeric assembly rather than another. Thus, in this mini-review, we exclusively discuss the main strategies for designing and building chiral aggregates in water from achiral porphyrin monomers, with particular regard to their chiroptical features.

Protonated achiral H(2)TPPS4 spontaneously self-arranges at acids pH and high ionic strength to build mesoscopic J-aggregates that are intrinsically chiral. According to the symmetry rule aggregation leads to a racemate that, however, can be unbalanced by chemical (chiral pollutants) or physical stimuli (as vortexing the solution). Vortexing the title racemate, in principle, might either induce chiral separation or chiral enrichment. Indeed, herein it is shown that vortices enable the resolution of this racemic solution exploiting the tendency to deposit, onto the quartz cuvette walls, of the enantiomer favored by the stirring sense. Simultaneously, over time, it was found that the opposite chiral conformation becomes prevalent in solution realizing a significant enantiomeric resolution. Therefore, after removing all stirring-favored chiral J-aggregate from the solution, the recovering and isolating of the desired enantiomers from the cuvette walls was successfully obtained without complex procedures. In this sense, it has been demonstrated that the stirring forces are executively able to fulfil the chiral separation in H(2)TPPS4 J-aggregates, employed as model of a self-assembled system in aqueous solution.

Fundamentals of Supramolecular Chirality, pp. ix-xi (2021) Free AccessIntroduction — Chirality: What Is It, What Is It For?Roberto PurrelloRoberto PurrelloDepartment of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania 95125, Italyhttps://doi.org/10.1142/9781800610255_0001Cited by:0 PreviousNext AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsRecommend to Library ShareShare onFacebookTwitterLinked InRedditEmail Abstract: Chirality, defined as "the property of an object of not being superim-posable with its mirror image", is widespread in the universe where it is expressed at different levels: from subatomic to galactic. In (bio) chemistry, chirality has two relevant levels: the molecular and the supramolecular ones. Both these levels have specific meanings, and biological systems are naturally organized in such a way that they may recognize and differently interact with molecules, which are identical in all physico-chemical properties but those deriving from their (chiral) three-dimensional shape… FiguresReferencesRelatedDetails Fundamentals of Supramolecular ChiralityMetrics Downloaded 92 times History PDF download

Porphyrinoids are extremely attractive for their electronic, optical, and coordination properties as well as for their versatile substitution at meso/β-positions. All these features allow porphyrinoids to behave as chiroptical hosts for chiral recognition by means of non-covalent interactions towards chiral guests. Over the years, chiral discrimination of chiral molecules such as amino acids, alcohols, amines, hydroxy-carboxylic acids, etc. has aroused the interest of the scientific community. Hence, this review aims to report on the progress to date by illustrating some relevant research regarding the chiral recognition of a multitude of chiral organic guests through several chiral mono- and bis-porphyrins via different spectroscopic techniques.

Fundamentals of Supramolecular Chirality, pp. 149-174 (2021) No AccessChapter 4: Chiral Memory and Its ApplicationsAlessandro D'Urso and Roberto PurrelloAlessandro D'UrsoDepartment of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania 95125, Italy and Roberto PurrelloDepartment of Chemical Sciences, University of Catania, Viale A. Doria 6, Catania 95125, Italyhttps://doi.org/10.1142/9781800610255_0005Cited by:0 PreviousNext AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsRecommend to Library ShareShare onFacebookTwitterLinked InRedditEmail Abstract: Transfer of chirality to self-assembled species is an interesting phenomenon that allows the induction of additional functionality to the supramolecular architectures. Exploiting the role of chiral templates, we elucidated how to design supramolecular systems able to memorize chiral information. Moreover, using the right combination of thermodynamic and kinetic pathways, on–off switches of stored chirality can be obtained. FiguresReferencesRelatedDetails Fundamentals of Supramolecular ChiralityMetrics History PDF download

The pivotal role played by potassium ions in the noncovalent synthesis of discrete porphyrin-calixarene nanostructures has been examined. The flattened-cone conformation adopted by the two cavities of octa-cationic calix[4]tube C4T was found to prevent the formation of complexes with well-defined stoichiometry between this novel water-soluble calixarene and the tetra-anionic phenylsulfonate porphyrin CuTPPS. Conversely, preorganization of C4T into a C-4v-symmetrical scaffold, triggered by potassium ion encapsulation (C4T@K+), allowed us to carry out an efficient hierarchical self-assembly process leading to 2D and 3D nanostructures. The stepwise formation of discrete CuTPPS/C4T@K+ noncovalent assemblies, containing up to 33 molecular elements, was conveniently monitored by UV/vis spectroscopy by following the absorbance of the porphyrin Soret band.

Antibiotics represent essential drugs to contrast the insurgence of bacterial infections in humans and animals. Their extensive use in livestock farming, including aquaculture, has improved production performances and food safety. However, their overuse can implicate a risk of water pollution and related antimicrobial resistance. Consequently, innovative strategies for successfully removing antibiotic contaminants have to be advanced to protect human health. Among them, photodegradation TiO2-driven under solar irradiation appears not only as a promising method, but also a sustainable pathway. Hence, we evaluated several composite TiO2 powders with H2TCPP, CuTCPP, ZnTCPP, and SnT4 porphyrin for this scope in order to explore the effect of porphyrins sensitization on titanium dioxide. The synthesis was realized through a fully non-covalent functionalization in water at room conditions. The efficacy of obtained composite materials was also tested in photodegrading oxolinic acid and oxytetracycline in aqueous solution at micromolar concentrations. Under simulated solar irradiation, TiO2 functionalized with CuTCPP has shown encouraging results in the removal of oxytetracycline from water, by opening the way as new approaches to struggle against antibiotic's pollution and, finally, to represent a new valuable tool of public health.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in the front-line setting. Thereafter, two other proteasome inhibitors (carfilzomib and ixazomib), designed to overcome resistance to bortezomib, have been approved for treatment-experienced patients, and a variety of novel inhibitors are currently under preclinical and clinical investigation not only for haematological malignancies but also for solid tumours. However, since UPS collapse leads to toxic misfolded proteins accumulation, proteasome is attracting even more interest as a target for the care of neurodegenerative diseases, which are sustained by UPS impairment. Thus, conceptually, proteasome activation represents an innovative and largely unexplored target for drug development. According to a multidisciplinary approach, spanning from chemistry, biochemistry, molecular biology to pharmacology, this review will summarize the most recent available literature regarding different aspects of proteasome biology, focusing on structure, function and regulation of proteasome in physiological and pathological processes, mostly cancer and neurodegenerative diseases, connecting biochemical features and clinical studies of proteasome targeting drugs.