Porphyrin-Based Hybrid Nanohelices: Cooperative Effect between Molecular and Supramolecular Chirality on Amplified Optical Activity.

The development of chiral receptors for discriminating the configuration of the analyte of interest is increasingly urgent in view of monitoring pollution in water and waste liquids. Here, we investigate an easy protocol to immobilize the desired non-water-soluble receptors inside a water-dispersible chiral nanoplatform made of silica. This approach induces chirality in the receptors and Here, we investigate an easy protocol to immobilize the desired non-water-soluble receptors inside a water-dispersible chiral nanoplatform made of silica. This approach induces chirality in the receptors and makes the dye@nanohelix system disperse in a suspension of water without aggregation. We noted strong induction and amplification of chiroptical activity in both achiral and chiral (proline-based or hemicucurbituril-based) porphyrin derivatives with and without zinc ions once confined and organized in nanometer silica helices. The results clearly demonstrated that the organization-induced chirality amplification of porphyrins dominates the molecular chirality, and the amplification is more efficient for more flexible porphyrins (especially free-base and achiral).

Chiral Recognition by Supramolecular Porphyrin-Hemicucurbit[8]uril-Functionalized Gravimetric Sensors.

Enantiorecognition of a chiral analyte usually requires the ability to respond with high specificity to one of the two enantiomers of a chiral compound. However, in most cases, chiral sensors have chemical sensitivity toward both enantiomers, showing differences only in the intensity of responses. Furthermore, specific chiral receptors are obtained with high synthetic efforts and have limited structural versatility. These facts hinder the implementation of chiral sensors in many potential applications. Here, we utilize the presence of both enantiomers of each receptor to introduce a novel normalization that allows the enantio-recognition of compounds even when single sensors are not specific for one enantiomer of a target analyte. For this purpose, a novel protocol that permits the fabrication of a large set of enantiomeric receptor pairs with low synthetic efforts by combining metalloporphyrins with (R,R)- and (S,S)-cyclohexanohemicucurbit[8]uril is developed. The potentialities of this approach are investigated by an array of four pairs of enantiomeric sensors fabricated using quartz microbalances since gravimetric sensors are intrinsically non-selective toward the mechanism of interaction of analytes and receptors. Albeit the weak enantioselectivity of single sensors toward limonene and 1-phenylethylamine, the normalization allows the correct identification of these enantiomers in the vapor phase indifferent to their concentration. Remarkably, the achiral metalloporphyrin choice influences the enantioselective properties, opening the way to easily obtain a large library of chiral receptors that can be implemented in actual sensor arrays. These enantioselective electronic noses and tongues may have a potential striking impact in many medical, agrochemical, and environmental fields.

Synthesis and Characterization of New-Type Soluble ß-Substituted Zinc Phthalocyanine Derivative of Clofoctol.

In this work, we have described the synthesis and characterization of novel zinc (II) phthalocyanine bearing four 2-(2,4-dichloro-benzyl)-4-(1,1,3,3-tetramethyl-butyl)-phenoxy substituents on the peripheral positions. The compound was characterized by elemental analysis and different spectroscopic techniques, such as FT-IR, 1H NMR, MALDI-TOF, and UV-Vis. The Zn (II) phthalocyanine shows excellent solubility in organic solvents such as dichloromethane (DCM), n-hexane, chloroform, tetrahydrofuran (THF), and toluene. Photochemical and electrochemical characterizations of the complex were performed by UV-Vis, fluorescence spectroscopy, and cyclic voltammetry. Its good solubility allows a direct deposition of this compound as film, which has been tested as a solid-state sensing material in gravimetric chemical sensors for gas detection, and the obtained results indicate its potential for qualitative discrimination and quantitative assessment of various volatile organic compounds, among them methanol, n-hexane, triethylamine (TEA), toluene and DCM, in a wide concentration range.

Chiral Porphyrin Assemblies Investigated by a Modified Reflectance Anisotropy Spectroscopy Spectrometer.

Reflectance anisotropy spectroscopy (RAS) has been largely used to investigate organic compounds: Langmuir-Blodgett and Langmuir-Schaeffer layers, the organic molecular beam epitaxy growth in situ and in real time, thin and ultrathin organic films exposed to volatiles, in ultra-high vacuum (UHV), in controlled atmosphere and even in liquid. In all these cases, porphyrins and porphyrin-related compounds have often been used, taking advantage of the peculiar characteristics of RAS with respect to other techniques. The technical modification of a RAS spectrometer (CD-RAS: circular dichroism RAS) allows us to investigate the circular dichroism of samples instead of the normally studied linear dichroism: CD-RAS measures (in transmission mode) the anisotropy of the optical properties of a sample under right and left circularly polarized light. Although commercial spectrometers exist to measure the circular dichroism of substances, the "open structure" of this new spectrometer and its higher flexibility in design makes it possible to couple it with UHV systems or other experimental configurations. The importance of chirality in the development of organic materials (from solutions to the solid state, as thin layers deposited-in liquid or in vacuum-on transparent substrates) could open interesting possibilities to a development in the investigation of the chirality of organic and biological layers. In this manuscript, after the detailed explanation of the CD-RAS technique, some calibration tests with chiral porphyrin assemblies in solution or deposited in solid film are reported to demonstrate the quality of the results, comparing curves obtained with CD-RAS and a commercial spectrometer.

Stereospecific Self-Assembly Processes of Porphyrin-Proline Conjugates: From the Effect of Structural Features and Bulk Solvent Properties to the Application in Stereoselective Sensor Systems.

Conjugating the porphyrin ring with an amino acid via amide linkage represents a straightforward way for conferring both amphiphilicity and chirality to the macrocycle. Proline residue is a good choice in this context since its conformational rigidity allows for porphyrin assembling where molecular chirality is efficiently transferred and amplified using properly honed aqueous environments. Herein, we describe the evolution of the studies carried out by our group to achieve chiral systems from some porphyrin-proline derivatives, both in solution and in the solid state. The discussion focuses on some fundamental aspects reflecting on the final molecular architectures obtained, which are related to the nature of the appended group (stereochemistry and charge), the presence of a metal ion coordinated to the porphyrin core and the bulk solvent properties. Indeed, fine-tuning the mentioned parameters enables the achievement of stereospecific structures with distinctive chiroptical and morphological features. Solid films based on these chiral systems were also obtained and their recognition abilities in gaseous and liquid phase are here described.

The increased cortisol levels with preserved rhythmicity in aging and its relationship with dementia and metabolic syndrome.

BACKGROUND: In the aging process, the cumulative exposure to stress with increased cortisol levels is considered to be associated to the senescence itself and its related disorders. AIMS: To evaluate the role of cortisol in elderly subjects, with or without dementia, by the means of the AGICO study. METHODS: The AGICO study enrolled patients from ten Geriatric Units in Italy in 2012-2017 (Study Director Prof Paolo Falaschi, S. Andrea Hospital of Rome). Every subject received a comprehensive geriatric assessment (including the Mini-Mental State Examination, MMSE), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal). RESULTS: The MMSE was inversely related to the standardized diurnal and nocturnal urinary cortisol levels (p < 0.025 and p < 0.01, respectively) and the age was positively related (p < 0.01 and p < 0.001, respectively). The ratio between the standardized diurnal and nocturnal urinary cortisol levels was 1.50 ± 1.2 (mean ± standard deviation) and it was not modified by the age or dementia. The standardized diurnal and nocturnal urinary cortisol levels were significantly higher in patients with dementia (MMSE < 24) (p < 0.01). In the analysis of the subgroups with MetS, the highest concentrations of diurnal and nocturnal cortisol were found in patients with both dementia and MetS (p < 0.025 and p < 0.01, respectively). DISCUSSION: The AGICO study showed that the stress response significantly and progressively increases with age. CONCLUSION: The cortisol increase in aging is related to the presence of both dementia and metabolic syndrome.

Modulation of the 20S Proteasome Activity by Porphyrin Derivatives Is Steered through Their Charge Distribution.

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.

Advances in Optical Sensors for Persistent Organic Pollutant Environmental Monitoring.

Optical chemical sensors are widely applied in many fields of modern analytical practice, due to their simplicity in preparation and signal acquisition, low costs, and fast response time. Moreover, the construction of most modern optical sensors requires neither wire connections with the detector nor sophisticated and energy-consuming hardware, enabling wireless sensor development for a fast, in-field and online analysis. In this review, the last five years of progress (from 2017 to 2021) in the field of optical chemical sensors development for persistent organic pollutants (POPs) is provided. The operating mechanisms, the transduction principles and the types of sensing materials employed in single selective optical sensors and in multisensory systems are reviewed. The selected examples of optical sensors applications are reported to demonstrate the benefits and drawbacks of optical chemical sensor use for POPs assessment.

Chirality induction to achiral molecules by silica-coated chiral molecular assemblies.

Hybrid silica-organic nanohelices are used to organize a large variety of nonchiral small organic molecules or inorganic anions to nanometer-sized assemblies. Such chiral organization of achiral molecules induces chiroptical properties as detected by vibrational or electronic circular dichroism (CD), as well as from circularly polarized luminescence (CPL).

The strength in Numbers! Porphyrin hybrid nanostructured materials for chemical sensing.

The development of chemical sensors is an urgent need for both environmental and health issues. The breakthrough needed for the advancement of these devices is the development of efficient receptors. Porphyrins have been widely used as sensing layers in chemical sensors, but their integration with nanostructures can greatly boost the performance of these macrocycles, improving from one side the stability of the sensing layer, and from the other, offering additional interaction mechanisms with target analytes. We present here some recent examples of hybrid materials prepared by the integration of porphyrins with metal and metal oxide nanoparticles, porphyrin-based metal organic frameworks and their exploitation as sensing layers in chemical sensors.

Recent Advances in Chemical Sensors Using Porphyrin-Carbon Nanostructure Hybrid Materials.

Porphyrins and carbon nanomaterials are among the most widely investigated and applied compounds, both offering multiple options to modulate their optical, electronic and magnetic properties by easy and well-established synthetic manipulations. Individually, they play a leading role in the development of efficient and robust chemical sensors, where they detect a plethora of analytes of practical relevance. But even more interesting, the merging of the peculiar features of these single components into hybrid nanostructures results in novel materials with amplified sensing properties exploitable in different application fields, covering the areas of health, food, environment and so on. In this contribution, we focused on recent examples reported in literature illustrating the integration of different carbon materials (i.e., graphene, nanotubes and carbon dots) and (metallo)porphyrins in heterostructures exploited in chemical sensors operating in liquid as well as gaseous phase, with particular focus on research performed in the last four years.

Seeding Chiral Ensembles of Prolinated Porphyrin Derivatives on Glass Surface: Simple and Rapid Access to Chiral Porphyrin Films.

An easy and fast method to achieve chiral porphyrin films on glass is herein reported. The on-surface formation of organized supramolecular architectures with distinctive and remarkable chiroptical features strictly depends on the macrocycles used, the solvent chosen for the casting deposition, and most importantly, on the roughness of the glass slide. Dynamic light scattering studies performed on 10-4-10-6 M porphyrin solutions revealed the presence of small porphyrin aggregates, whose size and number increase depending on the initial concentration. Once transferred on surface, these protoaggregates act as nucleation seeds for the following, self-assembling into larger structures upon solvent evaporation, with a process driven by a fine balance between intermolecular and molecule-substrate interactions. The described method represents a straightforward way to fabricate porphyrin-based chiral surfaces onto a transparent and economic substrate in few minutes. The results obtained can be particularly promising for the development of sensors based on stereoselective optical active films, targeting the detection of chiral analytes of practical relevance, such as the so-called emerging pollutants released in the environment from agrochemical, food, and pharmaceutical manufacturing.

Porphyrins Through the Looking Glass: Spectroscopic and Mechanistic Insights in Supramolecular Chirogenesis of New Self-Assembled Porphyrin Derivatives.

The solvent driven aggregation of porphyrin derivatives, covalently linked to a L- or D-prolinate enantiomer, results in the stereospecific formation of species featuring remarkable supramolecular chirality, as a consequence of reading and amplification of the stereochemical information stored in the proline-appended group. Spectroscopic, kinetic, and topographic SEM studies gave important information on the aggregation processes, and on the structures of the final chiral architectures. The results obtained may be the seeds for the construction of stereoselective sensors aiming at the detection, for example, of novel emergent pollutants from agrochemical, food, and pharmaceutical industry.

Tunable Supramolecular Chirogenesis in the Self-Assembling of Amphiphilic Porphyrin Triggered by Chiral Amines.

Supramolecular chirality is one of the most important issues in different branches of science and technology, as stereoselective molecular recognition, catalysis, and sensors. In this paper, we report on the self-assembly of amphiphilic porphyrin derivatives possessing a chiral information on the periphery of the macrocycle (i.e., D- or L-proline moieties), in the presence of chiral amines as co-solute, such as chiral benzylamine derivatives. The aggregation process, steered by hydrophobic effect, has been studied in aqueous solvent mixtures by combined spectroscopic and topographic techniques. The results obtained pointed out a dramatic effect of these ligands on the morphology and on the supramolecular chirality of the final self-assembled structures. Scanning electron microscopy topography, as well as fluorescence microscopy studies revealed the formation of rod-like structures of micrometric size, different from the fractal structures formerly observed when the self-assembly process is carried out in the absence of chiral amine co-solutes. On the other hand, comparative experiments with an achiral porphyrin analogue strongly suggested that the presence of the prolinate moiety is mandatory for the achievement of the observed highly organized suprastructures. The results obtained would be of importance for unraveling the intimate mechanisms operating in the selection of the homochirality, and for the preparation of sensitive materials for the detection of chiral analytes, with tunable stereoselectivity and morphology.

The Self-Aggregation of Porphyrins with Multiple Chiral Centers in Organic/Aqueous Media: The Case of Sugar- and Steroid-Porphyrin Conjugates.

An overview of the solvent-driven aggregation of a series of chiral porphyrin derivatives studied by optical methods (UV/Vis, fluorescence, CD and RLS spectroscopies) is herein reported. The investigated porphyrins are characterized by the presence in the meso-positions of glycol-, steroidal- and glucosteroidal moieties, conferring amphiphilicity and solubility in aqueous media to the primarily hydrophobic porphyrin platform. Aggregation of the macrocycles is driven by a change in bulk solvent composition, forming architectures with supramolecular chirality, steered by the stereogenic centers on the porphyrin peripheral positions. The aggregation behavior and chiroptical properties of the final aggregated species strongly depend on the number and stereogenicity of the ancillary groups that dictate the mutual spatial arrangement of the porphyrin chromophores and their further organization in larger structures, usually detectable by different microscopies, such as AFM and SEM. Kinetic studies are fundamental to understand the aggregation mechanism, which is frequently found to be dependent on the substrate concentration. Additionally, Molecular Mechanics calculations can give insights into the intimate nature of the driving forces governing the self-assembly process. The critical use of these combined methods can shed light on the overall self-assembly process of chirally-functionalized macrocycles, with important implications on the development of chiral porphyrin-based materials.

The Assembly of Porphyrin Systems in Well-Defined Nanostructures: An Update.

The interest in assembling porphyrin derivatives is widespread and is accounted by the impressive impact of these suprastructures of controlled size and shapes in many applications from nanomedicine and sensors to photocatalysis and optoelectronics. The massive use of porphyrin dyes as molecular building blocks of functional materials at different length scales relies on the interdependent pair properties, consisting of their chemical stability/synthetic versatility and their quite unique physicochemical properties. Remarkably, the driven spatial arrangement of these platforms in well-defined suprastructures can synergically amplify the already excellent properties of the individual monomers, improving conjugation and enlarging the intensity of the absorption range of visible light, or forming an internal electric field exploitable in light-harvesting and charge-and energy-transport processes. The countless potentialities offered by these systems means that self-assembly concepts and tools are constantly explored, as confirmed by the significant number of published articles related to porphyrin assemblies in the 2015-2019 period, which is the focus of this review.

ß-Arylethynyl substituted silver corrole complexes.

Silver corrolates are attractive compounds from both practical and theoretical points of view. Indeed, they play a key role in peripheral functionalization reactions occurring at the macrocycle, enabling high-yield and regioselective group insertions useful to further elaborate the molecular skeleton. In parallel, the Janus innocent or noninnocent behavior of the corrole ligand in these complexes makes their description particularly challenging. Herein, we report properties for a series of silver 3,17-disubstituted triarylcorrole complexes with various functionalities (halogens or different phenylethynyl units) that deeply affect the electron density in the macrocyclic ligand, with obvious repercussions on the observed spectral characteristics. The compounds were obtained in yields of 54-92% by applying the Stille coupling reaction with the appropriate tributylethynyl stannane. Among the complexes prepared was a derivative bearing two terminal acetylenic units which opens the way to "click" reactions for new corrole-based architectures. This corrole was structurally characterized by single crystal X-ray crystallography. The addition of substituted ethynyl groups resulted in red-shifts of the electronic absorption spectra, the largest of which was observed for the compound with two ß-NO2-Ph-C[triple bond, length as m-dash]C substituents. The remarkable influence of the NO2 groups on the electron density of this macrocycle was further demonstrated by electrochemical measurements, where an easier reduction of this complex derivative was observed as compared to the others. DFT calculations showed full delocalization over the entire p-nitrophenylethynyl unit of 5, largely affecting orbital distributions and the corresponding electronic absorptions. Although a variation of the ß-substituents dramatically modifies the Soret- and Q-band positions towards lower energies for all the examined complexes, the saddling of the macrocycle resulting from functionalization is only moderate. The collected results suggest the description of these compounds as AgIII-corrolate3-, a metallocorrole with an innocent macrocyclic ligand.

Chiral Selectivity of Porphyrin-ZnO Nanoparticle Conjugates.

Recognition of enantiomers is one of the most arduous challenges in chemical sensor development. Although several chiral systems exist, their effective exploitation as the sensitive layer in chemical sensors is hampered by several practical implications that hinder stereoselective recognition in solid state. In this paper, we report a new methodology to efficiently prepare chiral solid films, by using a hybrid material approach where chiral porphyrin derivatives are grafted onto zinc oxide nanoparticles. Circular dichroism (CD) evidences that the solid-state film of the material retains supramolecular chirality due to porphyrin interactions, besides an additional CD feature in correspondence of the absorbance of ZnO (375 nm), suggesting the induction of chirality in the underlying zinc oxide nanoparticles. The capability of hybrid material to detect and recognize vapors of enantiomer pairs was evaluated by fabricating gas sensors based on quartz microbalances. Chiral films of porphyrin on its own were used for comparison. The sensor based on functionalized nanostructures presented a remarkable stereoselectivity in the recognition of limonene enantiomers, whose ability to intercalate in the porphyrin layers makes this terpene an optimal chiral probe. The chiroptical and stereoselective properties of the hybrid material confirm that the use of porphyrin-capped ZnO nanostructures is a viable route for the formation of chiral selective surfaces.

Kinetic and spectroscopic studies on the chiral self-aggregation of amphiphilic zinc and copper (l)-prolinate-tetraarylporphyrin derivatives in different aqueous media.

The self-aggregation of inherently chiral, (l)-proline functionalised Cu and Zn porphyrin derivatives has been investigated in different aqueous organic solvent media. The results indicate that the title species form self-assembled structures expressing supramolecular chirality by the amplification of the stereochemical information stored on the l-prolinate functionality. A substantial difference of the aggregation modes, and the chiroptical features of the final supramolecular species for the two investigated complexes, is clearly imputable to the metal ions, having a different coordination ability toward solvent molecules. Detailed kinetic investigation performed by combining different spectroscopy techniques allowed the definition of the reaction mechanisms involved in these processes. The results described are of importance, for example, for the achievement of stereoselective devices and sensors.

Amphiphilic Porphyrin Aggregates: A DFT Investigation.

Owing to the attractive potential applications of porphyrin assemblies in photocatalysis, sensors, and material science, studies presently concerning porphyrin aggregation are widely diffused. π-π stacking, H-bonding, metal coordination, hydrophobic effect, and electrostatic forces usually drive porphyrin interaction in solution. However, theoretical studies of such phenomena are still limited. Therefore, a computational examination of the different porphyrin aggregation approaches is proposed here, taking into account amphiphilic [5-{4-(3-trimethylammonium)propyloxyphenyl}-10,15,20-triphenylporphyrin] chloride, whose aggregation behavior has been previously experimentally investigated. Different functionals have been adopted to investigate the porphyrin dimeric species, considering long-range interactions. Geometry optimization has been performed, showing that for the compound under analysis, H-type and cation-π dimers are the most favored structures that likely co-exist in aqueous solution. Of note, frontier orbital delocalization showed an interesting interaction between the porphyrin units in the dimer at the supramolecular level.