Unravelling the Antifibrinolytic Mechanism of Action of the 1,2,3-Triazole Derivatives.

A new family of antifibrinolytic drugs has been recently discovered, combining a triazole moiety, an oxadiazolone, and a terminal amine. Two of the molecules of this family have shown activity that is greater than or similar to that of tranexamic acid (TXA), the current antifibrinolytic gold standard, which has been associated with several side effects and whose use is limited in patients with renal impairment. The aim of this work was to thoroughly examine the mechanism of action of the two ideal candidates of the 1,2,3-triazole family and compare them with TXA, to identify an antifibrinolytic alternative active at lower dosages.

1,2,3-Triazole Derivatives as Novel Antifibrinolytic Drugs.

Fibrinolysis is a natural process that ensures blood fluidity through the removal of fibrin deposits. However, excessive fibrinolytic activity can lead to complications in different circumstances, such as general surgery or severe trauma. The current antifibrinolytic drugs in the market, aminocaproic acid (EACA) and tranexamic acid (TXA), require high doses repetitively to maintain their therapeutic effect.

Revising Protein Corona Characterization and Combining ITC and Nano-DSC to Understand the Interaction of Proteins With Porous Nanoparticles.

The exposure of nanoparticles (NPs) to biological fluids leads to the formation of a protein coating that is known as protein corona (PC). Since PC formation is influenced by the physicochemical properties of the nanoparticles, the understanding of the interplay of the factors that participate in this process is crucial for the development of nanomaterials as cell-targeted delivery vehicles. In general, it is accepted that the PC formation is a complex and dynamic process, which depends on the composition of the medium and the properties of the NP mainly size, shape, and superficial charge.

Nanoparticles for Triple Drug Release for Combined Chemo- and Photodynamic Therapy.

A pH-responsive drug delivery system (DDS) based on mesoporous silica nanoparticles (MSNs) has been prepared for the delivery of three anticancer drugs with different modes of action. The novelty of this system is its ability to combine synergistic chemotherapy and photodynamic therapy. A photoactive conjugate of a phthalocyanine (Pc) and a topoisomerase I inhibitor (topo-I), namely camptothecin (CPT), linked by a poly(ethylene glycol) (PEG) chain has been synthesized and then loaded into the mesopores of MSNs.

Preparation and Applications of Organo-Silica Hybrid Mesoporous Silica Nanoparticles for the Co-Delivery of Drugs and Nucleic Acids.

Combination therapies rely on the administration of more than one drug, with independent mechanisms of action, aiming to enhance the efficiency of the treatment. For an optimal performance, the implementation of such therapies requires the delivery of the correct combination of drugs to a specific cellular target. In this context, the use of nanoparticles (NP) as platforms for the co-delivery of multiple drugs is considered a highly promising strategy.

Glycyrrhetinic Acid-Functionalized Mesoporous Silica Nanoparticles for the Co-Delivery of DOX/CPT-PEG for Targeting HepG2 Cells.

A pH-triggered mesoporous silica nanoparticle (MSN)-based nano-vehicle for the dual delivery of doxorubicin (DOX)/camptothecin-PEG (CPT-PEG) has been prepared. To enhance its selectivity, the nanoparticles were decorated with glycyrrhetinic acid (GA) to target HepG2 cells. The highly insoluble CPT was derivatized with a reductive-cleavable PEG chain to improve its loading within the MSN.

Isothiocyanate-Functionalized Mesoporous Silica Nanoparticles as Building Blocks for the Design of Nanovehicles with Optimized Drug Release Profile.

A straightforward methodology for the synthesis of isothiocyanate-functionalized mesoporous silica nanoparticles (MSNs) by exposure of aminated MSNs to 1,1'-thiocarbonyldi-2(1)-pyridone is reported. These nanoparticles are chemically stable, water tolerant, and readily react with primary amines without the formation of any by-product. This feature allows the easy modification of the surface of the nanoparticles for tuning their physical properties and the introduction of gatekeepers on the pore outlets.

Extended 2,2'-Bipyrroles: New Monomers for Conjugated Polymers with Tailored Processability.

The synthesis of 2,2'-bipyrroles substituted at positions 5,5' with pyrrolyl, -methyl-pyrrolyl and thienyl groups and their application in the preparation of conducting polymers is reported herein. The preparation of these monomers consisted of two synthetic steps from a functionalized 2,2'-bipyrrole: Bromination of the corresponding 2,2'-bipyrrole followed by Suzuki or Stille couplings. These monomers display low oxidation potential compared to pyrrole because of the extended length of their conjugation pathway.

Functionalized 2,2'-Bipyrroles: Building Blocks for Pyrrolic Macrocycles.

Functionalized N-unsubstituted 2,2'-bipyrroles are basic building blocks for the preparation of pyrrolic macrocycles and natural products, such as prodigiosines. The aim of this review is to provide a description of the most important methodologies used to prepare 2,2'-bipyrroles and their central role as building blocks for the synthesis of porphyrinoids and property-defining structural elements therein.

Stable 5,5'-Substituted 2,2'-Bipyrroles: Building Blocks for Macrocyclic and Materials Chemistry.

The preparation and characterization of a family of stable 2,2'-bipyrroles substituted at positions 5 and 5' with thienyl, phenyl, TMS-ethynyl, and vinyl groups is reported herein. The synthesis of these new bipyrroles comprises three steps: formation of the corresponding 5,5'-unsubstituted bipyrrole, bromination, and Stille or Suzuki coupling. The best results in the coupling are obtained using the Stille reaction under microwave irradiation.

Porphycenes and Related Isomers: Synthetic Aspects.

Porphyrins, called the pigments of life, have been studied for decades. However, the first constitutional isomer of porphyrin, porphycene, was not synthesized until 1986. This milestone marked the beginning of a new era in the field of porphyrinoids and presented opportunities for the creation of an abundance of new pigments.

Quaterpyrroles as building blocks for the synthesis of expanded porphyrins.

A new family of quaterpyrroles and their application as building blocks for the synthesis of macrocycles is reported. The preparation of these quaterpyrroles consisted of two synthetic steps: bromination of 2,2'-bipyrroles bearing two electron-withdrawing groups followed by Suzuki coupling with 1-(tert-butoxycarbonyl)pyrrole-2-boronic acid. The resulting quaterpyrroles have been used to prepare an octaphyrin and a substituted cyclo[8]pyrrole.

Analysis of by-product formation and sugar monomerization in sugarcane bagasse pretreated at pilot plant scale: differences between autohydrolysis, alkaline and acid pretreatment.

Sugarcane bagasse is an interesting feedstock for the biobased economy since a large fraction is polymerized sugars. Autohydrolysis, alkaline and acid pretreatment conditions combined with enzyme hydrolysis were used on lignocellulose rich bagasse to acquire monomeric. By-products found after pretreatment included acetic, glycolic and coumaric acid in concentrations up to 40, 21 and 2.

Modifications of microvascular EC surface modulate phototoxicity of a porphycene anti-ICAM-1 immunoconjugate; therapeutic implications.

Inflammation and shear stress can upregulate expression of cellular adhesion molecules in endothelial cells (EC). The modified EC surface becomes a mediating interface between the circulating blood elements and the endothelium, and grants opportunity for immunotherapy. In photodynamic therapy (PDT), immunotargeting might overcome the lack of selectivity of currently used sensitizers.

Efficient induction of apoptosis in HeLa cells by a novel cationic porphycene photosensitizer.

In the present study we analyze the photobiological properties of 2,7,12-tris(α-pyridinio-p-tolyl)-17-(p-(methoxymethyl)phenyl) porphycene (Py3MeO-TBPo) in Hela cells, in order to assess its potential as a new photosensitizer for photodynamic therapy of cultured tumor cells. Using 0.5 μM Py3MeO-TBPo, flow cytometry studies demonstrated an increase of intracellular drug levels related to the incubation time, reaching a maximum at 18 h.

Synthesis, characterization, and photoinduced antibacterial activity of porphyrin-type photosensitizers conjugated to the antimicrobial peptide apidaecin 1b.

Antimicrobial photodynamic therapy (aPDT) is an emerging treatment for bacterial infections that is becoming increasingly more attractive because of its effectiveness against multi-antibiotic-resistant strains and unlikelihood of inducing bacterial resistance. Among the strategies to enhance the efficacy of PDT against Gram-negative bacteria, the binding to a cationic antimicrobial peptide offers the attractive prospect for improving both the water solubilty and the localization of the photoactive drug in bacteria. In this work we have compared a number of free and apidaecin-conjugated photosensitizers (PSs) differing in structure and charge.

Synthesis of 2-arylamino substituted 5,6-dihydropyrido[2,3-d]pyrimidine-7(8H)-ones from arylguanidines.

A practical protocol was developed for the synthesis of 2-arylamino substituted 4-amino-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones from α,β-unsaturated esters, malononitrile, and an aryl substituted guanidine via the corresponding 3-aryl-3,4,5,6- tetrahydropyrido[2,3-d]pyrimidin-7(8H)-ones. Such compounds are formed upon treatment of 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles with an aryl substituted guanidine in 1,4-dioxane and are converted to the desired 4-aminopyridopyrimidines with NaOMe/MeOH through a Dimroth rearrangement. The overall yields of this three-step protocol are, generally speaking, higher than the multicomponent reaction, previously developed by our group, between an α,β-unsaturated ester, malononitrile, and an aryl substituted guanidine.

Tautomerization in 2,7,12,17-tetraphenylporphycene and 9-amino-2,7,12,17-tetraphenylporphycene: influence of asymmetry on the direction of the transition moment.

Femtosecond transient absorption anisotropy studies have been performed for two porphycenes of different symmetry. In 2,7,12,17-tetraphenylporphycene, the chemical identity of two trans forms implies a change in the S(0)-S(1) transition-moment direction upon tautomerization. Exploiting this phenomenon, the rates of double hydrogen transfer in both the S(0) and S(1) states (1.

Dual fluorescence in 9-amino-2,7,12,17-tetraphenylporphycene.

The absorption spectrum of the asymmetric 9-amino-2,7,12,17-tetraphenylporphycene shows new, strongly red-shifted bands compared to the symmetric parental 2,7,12,17-tetraphenylporphycene and to the also asymmetric 9-acetoxy-2,7,12,17-tetraphenylporphycene. Dual emission is also observed with relative contributions that depend strongly on the excitation wavelength and temperature. The gap between the two fluorescence bands is 84 nm.

Cationic porphycenes as potential photosensitizers for antimicrobial photodynamic therapy.

Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines, and phenothiazinium salts, with cationic charges at physiological pH values. However, derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties.

Nanosized hybrid oligoamide foldamers: aromatic templates for the folding of multiple aliphatic units.

Oligoamide sequences comprised of both 8-amino-2-quinolinecarboxylic acid "Q" and 6-aminomethyl-2-pyridinecarboxylic acid "P" have been synthesized. It was found that the aliphatic amine of P greatly facilitates amide couplings, as opposed to the aromatic amine of Q, which enabled us to prepare sequences having up to 40 units. The conformation and conformational stability of these oligomers were characterized in the solid state using X-ray crystallography and in solution using NMR and various chromatographic techniques.

Singlet oxygen photosensitisation by the fluorescent probe Singlet Oxygen Sensor Green.

The fluorescent probe Singlet Oxygen Sensor Green is able to produce singlet oxygen under exposure to UV or visible radiation.

A bisfullerene-bis(dipyrrinato)zinc complex: electronic coupling and charge separation in an easy-to-assemble synthetic system.

Getting connected: The use of a bis(dipyrrinato)zinc(II)) linker allows the facile tethering of two C(60) subunits and gives rise to an electronically coupled system that allows effective charge separation following photoexcitation (see figure).

One-pot synthesis of substituted 2,2'-bipyrroles. A straightforward route to aryl porphycenes.

A one-pot reaction for the synthesis of 4,4'-diaryl- and 4,4'-diheteroaryl-substituted 2,2'-bipyrroles is described. The new methodology is based on the oxidative coupling of a 2-trimethylstannylated pyrrole and does not require chromatography. These 2,2'-bipyrroles can be used as precursors in a expeditious synthesis of 2,7,12,17-tetraaryl-porphycenes.