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.

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.

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.

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.

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.

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).

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.

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.

Porphyrinoids for Chemical Sensor Applications.

Porphyrins and related macrocycles have been intensively exploited as sensing materials in chemical sensors, since in these devices they mimic most of their biological functions, such as reversible binding, catalytic activation, and optical changes. Such a magnificent bouquet of properties allows applying porphyrin derivatives to different transducers, ranging from nanogravimetric to optical devices, also enabling the realization of multifunctional chemical sensors, in which multiple transduction mechanisms are applied to the same sensing layer. Potential applications are further expanded through sensor arrays, where cross-selective sensing layers can be applied for the analysis of complex chemical matrices. The possibility of finely tuning the macrocycle properties by synthetic modification of the different components of the porphyrin ring, such as peripheral substituents, molecular skeleton, coordinated metal, allows creating a vast library of porphyrinoid-based sensing layers. From among these, one can select optimal arrays for a particular application. This feature is particularly suitable for sensor array applications, where cross-selective receptors are required. This Review briefly describes chemical sensor principles. The main part of the Review is divided into two sections, describing the porphyrin-based devices devoted to the detection of gaseous or liquid samples, according to the corresponding transduction mechanism. Although most devices are based on porphyrin derivatives, seminal examples of the application of corroles or other porphyrin analogues are evidenced in dedicated sections.

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.

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.

Recent advances in the role of cortisol and metabolic syndrome in age-related degenerative diseases.

The metabolic syndrome (MetS) presents an increasing prevalence in elderly people. A significant role in MetS is played by the stress response and cortisol. The hypothalamic-pituitary-adrenal (HPA) axis activity is increased by central (loss of hippocampal glucocorticoid receptors) and peripheral (11ß-hydroxysteroid dehydrogenase type 1, 11ß-HSD1, hyperactivity) mechanisms. The HPA hyperactivity has been found in chronic diseases affecting the endocrine (abdominal obesity with MetS, type 2 diabetes), cardiovascular (atherosclerosis, essential hypertension), and nervous systems (dementia, depression), in aging. A novel therapeutic approach (11ß-HSD1 inhibition) is promising in treating the HPA axis hyperactivity in chronic diseases with MetS. A large-scale national clinical trial (AGICO, AGIng, and COrtisol study) has been proposed by our group to evaluate the role of cortisol and MetS in the main pathologies of aging (vascular and degenerative dementia, cardiovascular diseases, type 2 diabetes, abdominal obesity).

5,10,15-Triferrocenylcorrole Complexes.

Complexes of 5,10,15-triferrocenylcorrole were synthesized from the crude free-base corrole product obtained by the reaction of ferrocenyl aldehyde and pyrrole. Direct formation of the complex in this manner leads to an increase of the reaction yield by protecting the corrole ring toward oxidative decomposition. The procedure was successful and gave the expected product in the case of the copper and triphenylphosphinecobalt complexes, but an unexpected result was obtained in the case of the nickel derivative, where metal insertion led to a ring opening of the macrocycle at the 5 position, giving as a final product a linear tetrapyrrole nickel complex bearing two ferrocenyl groups. The purified 5,10,15-triferrocenylcorrole complexes have been fully characterized by a combination of spectroscopic methods, electrochemistry, spectroelectrochemistry, and density functional theory calculations. Copper derivatives of 10-monoferrocenyl- and 5,15-diferrocenylcorrole were prepared to investigate how the number and position of the ferrocenyl groups influenced the spectroscopic and electrochemical properties of the resulting complexes. A complete assignment of resonances in the (1)H and (13)C NMR spectra was performed for the cobalt and nickel complexes, and detailed electrochemical characterization was carried out to provide additional insight into the degree of communication between the meso-ferrocenyl groups on the conjugated macrocycle and the central metal ion of the ferrocenylcorrole derivatives.

New example of hemiporphycene formation from the corrole ring expansion.

The reaction of 5,10,15-tris(4-tert-butylphenyl)corrole with 2,3-bis(bromomethyl)-5,6-dicyanopyrazine provides a new example of corrole ring expansion to a hemiporphycene derivative. The ring expansion is regioselective, with insertion of the pyrazine derivative at the 5-position of the corrole ring, affording the corresponding 5-hemiporphycene. Different macrocyclic products accompany formation of the 5-hemiporphycene, depending on the reaction experimental conditions. Br-substitued 5-hemiporphycenes and the 2-Br substituted corrole were obtained in 1,2,4-trichlorobenzene, while in refluxing toluene traces of an inner core substituted corrole were observed together with a significant amount of the unreacted corrole. These results provide an important indication of the reaction pathway. The coordination behavior of the 5-hemiporphycene, together with detailed electrochemical characterization of the free-base and some metal complexes, provides evidence for the reactivity of the peripheral pyrazino group.

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).

Synthesis and characterization of functionalized meso-triaryltetrabenzocorroles.

5,10,15-Triaryltetrabenzocorroles functionalized with different electron-withdrawing groups on the ß,ß'-fused rings have been prepared by a cross-coupling Heck procedure between octabrominated copper corrole and a terminal alkene bearing electron-withdrawing moieties. The spectroscopic characterization of these complexes showed red-shifted UV-vis absorption bands characterized by a significant band broadening. The same feature was observed in the case of NMR spectra, where low-resolution groups of signals were observed. This behavior derives from a strong tendency of these macrocycles to aggregate in solution, as has been demonstrated by an (1)H NMR study performed on one of these tetrabenzocorroles. The influence of the substituents on the fused benzene ring on the properties of the tetrabenzocorroles was investigated by electrochemistry and spectroelectrochemistry, and comparisons were made between properties of the newly synthesized compounds and those of the tetrabenzocorroles reported earlier in the literature.

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.

ß-Nitro derivatives of iron corrolates.

Two different methods for the regioselective nitration of different meso-triarylcorroles leading to the corresponding ß-substituted nitrocorrole iron complexes have been developed. A two-step procedure affords three Fe(III) nitrosyl products-the unsubstituted corrole, the 3-nitrocorrole, and the 3,17-dinitrocorrole. In contrast, a one-pot synthetic approach drives the reaction almost exclusively to formation of the iron nitrosyl 3,17-dinitrocorrole. Electron-releasing substituents on the meso-aryl groups of the triarylcorroles induce higher yields and longer reaction times than what is observed for the synthesis of similar triarylcorroles with electron-withdrawing functionalities, and these results can be confidently attributed to the facile formation and stabilization of an intermediate iron corrole π-cation radical. Electron-withdrawing substituents on the meso-aryl groups of triarylcorrole also seem to labilize the axial nitrosyl group which, in the case of the pentafluorophenylcorrole derivative, results in the direct formation of a disubstituted iron µ-oxo dimer complex. The influence of meso-aryl substituents on the progress and products of the nitration reaction was investigated. In addition, to elucidate the most important factors which influence the redox reactivity of these different iron nitrosyl complexes, selected compounds were examined by cyclic voltammetry and thin-layer UV-visible or FTIR spectroelectrochemistry in CH(2)Cl(2).

ß-Nitro-5,10,15-tritolylcorroles.

Functionalization of the ß-pyrrolic positions of the corrole macrocycle with -NO(2) groups is limited at present to metallocorrolates due to the instability exhibited by corrole free bases under oxidizing conditions. A careful choice of the oxidant can limit the transformation of corroles into decomposition products or isocorrole species, preserving the corrole aromaticity, and thus allowing the insertion of nitro groups onto the corrole framework. Here we report results obtained by reacting 5,10,15-tritolylcorrole (TTCorrH(3)) with the AgNO(2)/NaNO(2) system, to give mono- and dinitrocorrole derivatives when stoichiometry is carefully controlled. Reactions were found to be regioselective, affording the 3-NO(2)TTCorrH(3) and 3,17-(NO(2))(2)TTCorrH(3) isomers as the main products in the case of mono- and disubstitution, in 53 and 20% yields, respectively. In both cases, traces of other mono- and disubstituted isomers were detected, which were structurally characterized by X-ray crystallography. The influence of the ß-nitro substituents on the corrole properties is studied in detail by UV-visible, electrochemical, and spectroelectrochemical characterization of these functionalized corroles. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations of the ground and excited state properties of these ß-nitrocorrole derivatives also afforded significant information, closely matching the experimental observations. It is found that the ß-NO(2) substituents conjugate with the π-aromatic system of the macrocycle, which initiates significant changes in both the spectroscopic and redox properties of the so functionalized corroles. This effect is more pronounced when the nitro group is introduced at the 2-position, because in this case the conjugation is, for steric reasons, more efficient than in the 3-nitro isomer.