80 research outputs found
A multidisciplinary approach to the development of innovative tools for pharmaceutical and technological applications
The research activity carried out during the Ph.D. in Chemical and Pharmaceutical Sciences has regarded the design, synthesis, and characterization of innovative tools relevant to both pharmaceutical and technological fields. Great interest has been dedicated to the investigation of the “affinity polymerization” mechanism of novel polymeric materials founded on repetitive monomeric units based on the 3-phenylbenzofulvene scaffold that spontaneously polymerize by simple removal of the solvent. In this context, the attention has been focused on the synthesis of novel benzofulvene-based derivatives bearing complexed and non-complexed pyridine rings in different positions of the benzofulvene scaffold, to evaluate the effects generated by the insertion of a bulky substituent in the aggregation/polymerization behavior. The experience acquired with this study has been then capitalized on the design, synthesis, and characterization of a novel visible-light-sensitive biomimetic molecular switch inspired by the benzofulvene scaffold and the Green Fluorescent Protein (GFP) chromophore. The chemical-structural manipulation of the benzofulvene structure has made possible the development of a novel set of biomimetic photoswitches inspired by the supramolecular properties of the 3-phenylbenzofulvene scaffold and the molecular features of the GFP chromophore.
In the framework of material chemistry, the well-known click-chemistry reaction of hyaluronic acid (HA) derivatives bearing propargylated ferulic groups has been exploited to obtain biomimetic and biocompatible materials useful in different biopharmaceutical fields. In particular, low molecular weight HA has been anchored on the hydrophobic surface of low-generation poly(propylene imine) (PPI) dendrimers by the click-chemistry reaction between their azido-functionalized surfaces and low molecular weight HA derivatives bearing propargylated ferulic groups. The resulting materials have been proposed as biocompatible drug delivery systems (DDSs) of Doxorubicin. Another application of HA has concerned the hyaluronan-based graft copolymers showing low and medium molecular weight values that have been exploited in cross-linking by the click-chemistry reaction. Interestingly, the interaction of resulting HA materials with water led to the formation of hydrogels, and the tunable rheological behavior of these materials led to their applicability in different biomedical fields.
Lastly, the knowledge in medicinal chemistry has guided the design and synthesis of innovative bioactive compounds such as novel Cyclooxygenase‑2 (COX-2) inhibitors containing Nitric Oxide (NO) donor moiety (CINODs) endowed with vasorelaxant properties.
The outcomes of these studies would provide fertile ground for future projects that will hopefully contribute to accelerate the research in several fields. Indeed, the increased knowledge on the behavior of these innovative tools, by means of a multidisciplinary approach, is the key for boosting the development of novel materials for pharmaceutical and technological applications
Novel Wastewater Treatment Applications Using Polymeric Materials
This reprint focuses on the effective removal of organic and inorganic pollutants from water and wastewater using unique freestanding polymeric-based methods. It also examines innovative green methods for efficiently reusing various solid waste products. In addition, several new eco-friendly hybrid materials are being reviewed in order to alleviate the problem of water pollution in novel, rapid, and efficient methods
Exclusive Feature Papers in Colorants
“Exclusive Feature Papers in Colorants” is a collection of important high-quality papers (original research articles or comprehensive review papers) published in open access. This Special Issue aims to discuss new knowledge or new cutting-edge developments in the colorants research field through selected works, in the hope of making a great contribution to the community. We intend for this issue to be the best forum for disseminating excellent research findings as well as sharing innovative ideas in the field
New Trends in Asymmetric Catalysis
The synthesis of enantiopure organic compounds is a key issue for several applications in pharmacology, food chemistry, agricultural chemistry, perfumery, materials science and other industrial sectors. Nowadays, asymmetric catalysis is undoubtedly the most important tool to achieve this goal. This technology, in fact, enables the production of large amounts of enantiomerically enriched compounds, employing relatively small quantities of chiral enantiopure catalysts, which is exactly what is accomplished by enzymes in nature. Since the pioneering works of Noyori, Knowles and Sharpless, which later earned them the Nobel Prize in Chemistry, asymmetric catalysis has experienced a rapid and relentless development in the last fifty years. The tremendous expansion of enantioselective transformations, the design of novel and more efficient organometallic and organic catalysts, the development of sophisticated bioreactors and cell factories, are just some of the elements responsible for such growth. However, new challenges of asymmetric catalysis are devoted to enhancing the process’s sustainability, by the introduction of recyclable and low-cost catalysts, and the use of renewable starting materials and energy source. This book provides an overview of some of these development directions and comprises a collection of review papers and a research article authored by renowned researchers actively involved in this field. The topics covered by the review papers are photoredox-catalyzed reactions of imines, asymmetric catalytic electrosynthesis, cooperative catalysis of chiral N-heterocyclic carbenes and Lewis acid, and asymmetric ring-opening reactions of epoxides catalyzed by metal–salen complexes. The research article presents a proline-catalyzed aldol reaction in water–methanol solvent mixture
Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications
This Special Issue, entitled "Synthetic Peptides and Peptidomimetics: From Basic Science to Biomedical Applications", has included both reviews and original research contributions focused on the chemical design and biomedical applications of structurally modified bioactive peptides. The papers collected show how successful this class of molecules still is, both as model molecules for studying the structure of proteins and as potential therapeutics and diagnostics, and also as laboratory tools for advanced basic and applied studies. The large scientific community working in this field is in fact very active and productive, and is making the most of the potential and versatility of these molecules to generate increasingly interesting and innovative molecules of therapeutic interest and to understand the fundamental molecular mechanisms of life
Development Of New Photochemical Tools For Applications In Cancer Research And Enzymatic Signaling
Photochemical tools empower researchers to act with precision and control over the cellular environment through production of reactive oxygen species (ROS), targeted drug delivery, and modulation of enzymatic activity. These molecular tools use light as a readily available, biorthogonal reagent for initiating advantageous light-activated reactions. Using light in this way allows researchers to affect the cellular environment in specific ways with high spatio-temporal control. This dissertation focuses on expanding the applications of, mostly Ru(II)-based, photoactivated chemicals. Complexes of this type are able to act as photosensitizers in photodynamic therapy (PDT), as photocages (PCT), or as dual-action compounds capable of both PDT and PCT. Five projects were carried out in this work, and while the specifics differ from project to project, we can derive lessons from the collective work and apply it to the field as a whole. In this work, due to physical limitations in ligand construction, the capacity of the applied Ru(II) polypyridyl complexes to act as efficient photosensitizers. The Ru(II) complexes applied here have, however, displayed excellent capacity to act as photocages, both singularly and as a component in dualaction complexes. Optimization of Ru(II) complexes for photocaging consequential ligands is a research area ripe for innovation
Biomimetic Based Applications
The interaction between cells, tissues and biomaterial surfaces are the highlights of the book "Biomimetic Based Applications". In this regard the effect of nanostructures and nanotopographies and their effect on the development of a new generation of biomaterials including advanced multifunctional scaffolds for tissue engineering are discussed. The 2 volumes contain articles that cover a wide spectrum of subject matter such as different aspects of the development of scaffolds and coatings with enhanced performance and bioactivity, including investigations of material surface-cell interactions
Towards the synthesis of multinuclear, branched and cyclic metallocene-containing complexes
Branched and cyclic multinuclear metallocene systems are of great interest due to their remarkable chemical and physical properties, which often differ greatly to their mononuclear, or linear, analogues. In particular, the presence of multiple redox centres, either directly covalently bound or linked by conjugated organic motifs, offers the prospect of studying a plethora of electronic features, such as electron transfer, electronic communication between redox centres and multi-valence states. Due to its easily accessible analogues, ease of handling, and redox properties, ferrocene-containing systems are by far the most studied. Investigation of such multinuclear species has been hindered by synthetic issues arising from the flexibility of the metallocene, resulting in complex synthetic procedures and low yields.
Described herein is the optimisation of the preparation of valuable bi- and tri-ferrocenyl synthons, Fc2I2 and Fc3I2, respectively, via the traditional route of halogenation of the lithiated intermediate. Ultimately, an improved methodology in which dilithioferrocene was reacted directly with diiodoferrocene (FcI2) gave notably improved yields of the multinuclear systems. To achieve covalently bonded metallocenes, Suzuki-Miyaura and Ullmann-like couplings were explored. Although mono-ferrocenyl boronic acids could be prepared, the bi-ferrocenyl derivatives could not and attempts to couple these to iodoferrocenes were unsuccessful. Such reactions resulted mainly in hydrodehalogenation products and degradation, however, in some cases, intramolecular cyclisation of Fc2I2 was observed under Suzuki-Miyaura conditions.
Replacing the NMP medium used in the CuTc-mediated Ullmann-like coupling of iodoferrocenes with acetonitrile revealed a change in reactivity. This allowed a competing oxygen arylation reaction, in which the thiophene carboxylate moiety is transferred from the copper centre to the Cp rings of ferrocene, to take place in tandem. The combination of both the C-C and C-O bond forming reactions allowed for the isolation of a series of ferrocene-based thiophene carboxylate derivatives. The same reactivity pathway gave the ruthenocene analogues in both NMP (N-methyl pyrrolidone) and acetonitrile solvents. The mono- and bis-metallocenyl thiophene carboxylate adducts were transformed into the corresponding metallocenol by means of a base-mediated ester hydrolysis reaction. Overall, this revealed a modified reaction pathway towards oxygen substituted metallocenes, the higher order analogues of which are novel.
A number of related synthetic pathways were explored for the preparation of branched and cyclic ethynylarene-containing materials, which heavily featured subsequent Sonogashira couplings and alkyne protection/deprotection strategies. Essentially, the nature of the organic functionalities introduced to both the bridging and terminal positions was found to dictate the efficacy of a given methodology. A series of novel, branched ferrocene systems, containing diethynylpyridine, diethynylbipyridine and diethynylthiophene bridging moieties, were prepared with a variety of terminal ligands by utilising symmetric and asymmetric protecting group strategies. It was found that materials containing the bipyridyl motif, in either the bridging or terminal positions, presented the most complications with regards to preparation and isolation. Attempts to synthesise analogous cyclic systems via both Sonogashira couplings and Ullmann-like couplings were also made with limited success, owing to the formation of side products and degradation of starting materials under the chosen conditions. This resulted in the isolation of a novel diethynylpyridine-bridged tris-ferrocenyl macrocycle as well as evidence of the analogous thiophenyl species. Evidence was also found for the formation of hydrodehalogenation products from the starting material utilised in the attempted Ullmann-like cyclisation reactions.Open Acces
Bio-orthogonal conjugation for “wiring” redox-active proteins/enzymes to any conductive surface
This thesis first illustrates the utility and limitations of protein film electrochemistry of adsorbed species via the analysis of a fungal Lytic Polysaccharide Monooxygenase enzyme. While a useful enzyme assay of H2O2 reduction is developed, detailed analysis of the underpinning reversible enzyme electron transfer processes is limited by background redox contributions from the carbon nanotubes which are required to stabilise the enzyme in an electroactive configuration. The rest of this thesis describes the development of methodologies for achieving electroactive immobilisation of redox proteins/enzymes onto electrode surfaces. Electroactive immobilisation of redox proteins/enzymes via covalent bonds has applications in the fabrication of biosensors and the development of green technologies/biochemical synthetic approaches, yet most published methodologies for achieving covalent immobilisation of proteins have relied on performing ligations between amine-reactive motifs on electrode surfaces and protein lysine residues. This results in many redox proteins/enzymes becoming immobilised in non-electroactive orientations or in orientations that otherwise hinder the redox enzyme’s ability to perform catalysis. In an effort to address this, methodologies for the incorporation of bio-orthogonal aldehyde motifs into proteins were investigated, and a protein immobilisation approach was developed in which hydroxylamine-functionalised electrode surfaces undergo bio-orthogonal ligation to aldehyde-functionalised proteins. As characterising and controlling surface chemistries is notoriously difficult, a new method is also under development that aims to enable covalent orientation-selective electroactive redox protein/enzyme immobilisation via the direct electro-grafting of redox proteins/enzymes that have been site-specifically labelled with aryl diazonium cations. I report the first ever usage of triazabutadienes as photocaged sources of aryl diazonium cations for use as electrode derivatisation agents in aqueous solutions at near-neutral pH, and, to the best of my knowledge, the first site-specific installations of triazabutadienes/diazonium cations onto the surfaces of proteins. I hope that further development of this method will enable the orientation-selective electroactive immobilisation of redox proteins/enzymes
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