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  • 52 Reads
Bioactive diterpenoids obtained from Grindelia ventanensis Bartola & Tortosa(Asteraceae)

Grindelia ventanensis (Asteraceae) is an endemic species growing wildly in Sierra de la Ventana, southwest of Buenos Aires province, Argentina. Grindelia species, are characterized by the production of bicyclic labdane-type diterpenoids.

In a previous study we reported the cholinesterase inhibition observed for the ethanolic extract of G. ventanensis and the isolation of an active metabolite, 17-hydroxycativic acid, which showed antioxidant activity and moderate acetylcholinesterase (AChE) inhibition, without cytotoxic activity [1]. In this work, we focused our attention on the dichloromethane (DCM) extract of this plant, and its components, looking forward to identify other bioactive cativic acid analogs.

DCM extract showed strong antioxidant activity (IC50 = 27.03 μg/mL) detected by the reduction of DPPH and good AChE inhibition (IC50 =121.9 µg/mL). Then, this extract was fractionated by column chromatography and HPLC. Six diterpenoids were isolated and identified as 13-methyl-17-oxo-labda-7,13-diene-15-oic acid (1), 17-hydroxy-13-methyl-labda-7,13-diene-15-oic acid, 18-acetoxy-17-hydroxy cativic acid, 17-acetoxycativic acid, cativic acid and grindelic acid. These compounds were identified by RMN and MS analysis.

All the isolated diterpenoids were evaluated as AChE inhibitors and radical scavengers.

Compound 1 elicited the best results in both bioassays, with IC50 = 11.04 µM in the AChE inhibition test and an antioxidant activity comparable to trolox, the reference antioxidant (IC50 = 7.13 µM). Significant bioactivity was also observed for the rest of the isolated compounds.

These results suggest that G. ventanensis could be a source of bioactive compounds that may be of interest for the development of potential new alternatives in the treatment of Alzheimer's disease.

  • Open access
  • 24 Reads
Perturbation Methods for Obtaining Interactions Energies. Can SAPT2+/jun-cc-pVDZ predict adequate interaction energies when biochemically relevant motifs are present?

In the field of non-covalent interactions, there has always been a great interest in finding the appropriate methodology to analyze bond energies and properties. There are multiple approaches; however, those based on symmetry adapted perturbation theory (SAPT) are interesting for two different reasons: quality of the interaction energy and how it is obtained. Total interaction energies are computed in SAPT as the sum of the electrostatic, repulsive, inductive and dispersive components. This provides enormous information about the intimate nature of intermolecular interactions.

The performance of a variety of symmetry adapted perturbation theory (SAPT) methods for describing non-covalent interactions has been tested in several studies. The appropriate level depends to a certain degree on the nature of the interaction and the nature of the database, however, there is a methodological combination that can be considered as a reference. The SAPT2+(3)δMP2 truncation combined with the aug-cc-pVTZ basis set offers an outstanding performance for the majority of non-covalent complexes. This methodology produces interaction energies of excellent quality with low relative errors and little error spread so it can be adopted as a methodology to obtain reference energies for most applications of interest in chemistry and biochemistry. The problem that SAPT2+(3)δMP2/aug-cc-pVTZ faces is the computational resources demanded. These requirements grow enormously with size so that it soon becomes unfeasible for most systems of interest in biochemistry.

When the computational cost is prohibitively high it has been suggested the use of SAPT2+ level in combination with the jun-cc-pVDZ basis set. This methodology is known to give remarkable results at a reduced computational cost.

In this work, the goodness of the SAPT2+ methodology to produce interaction energies of non-covalent systems is explored using the so-called blind database. This database consists on a set of dimers bearing different type of interactions at equilibrium and non-equilibrium distances. Likewise, the SAPT2+/jun-cc-pVDZ methodology is employed to describe a set of prototypical interactions found in biochemical systems involving sugars, proteins and nucleic acids.

  • Open access
  • 34 Reads
Reactions of exo-exo-hexacyclo[,10.03,8.04,6.05,9]tetradecane with aliphatic alcohols under the action of ionic liquids

Despite the existence of a wide range of known catalysts, chemical engineering and organic synthesis is constantly in need of new, more efficient and environmentally acceptable catalysts and reaction media. Ionic liquids (ILs) meet these requirements. For example, ILs based on aluminum, iron, and other metal halides are an alternative to traditional catalysts, in particular, they catalyze Friedel-Crafts alkylation and acylation reactions, hydrogenation, and isomerization of alkanes and polycyclic hydrocarbons.

On the other hand, the chemistry of small cycles is an intensively developing branch of organic chemistry. Three-carbon rings are unique fragments that, due to their significant stress, are capable of unusual structural transformations with expansion and rearrangement of the small ring.

The reactions of cyclopropane compounds have been actively studied for more than three decades. In the world literature, there are very few examples of works on the functionalization of highly stressed cyclopropane-containing polycyclic hydrocarbons, the reaction products of which can be widely used as precursors for the synthesis of drugs, depressant additives to rocket fuels, and also as transmission media and working fluids. In addition, the analysis of literature data showed that ring-opening reactions of cyclopropanes are catalyzed mainly by transition metal complexes and there are no examples of the use of ILs as catalysts or their transformations.

In this work, we have developed new methods for the synthesis of previously undescribed 4-exo-alcoxypentacyclo[,8.02,9.03.7]tetradecanes by the reaction of a saturated dimer of norbornadiene - exo-exo-hexacyclo[,10.03,8.04,6.05.9]tetradecane with aliphatic alcohols C1-C4 under the action of ILs.

  • Open access
  • 34 Reads
Organophosphorus Chemistry: Synthesis of new phosphonic acid derivatives bearing a triazole moiety

The 1,2,3-triazole ring is a privileged building block in synthetic organic chemistry with well established and outstanding properties in medicinal chemistry. On the other hand, there is an extensive interest in synthetic organic methodologies for the construction of new phosphorus-containing molecules, due to the remarkable biological activities of many of these derivatives. In continuation of our search for new potentially bioactive phosphonates, we present herein the preliminary results in the synthesis of new 1,2,3-triazolylphosphonates, combining simple and efficient methodologies developed in our research group.

First, β-ketophosphonates obtained by a procedure that involved the use of copper nanoparticles supported on zinc oxide, were transformed into the corresponding β-azidophosphonates through subsequent reduction, mesylation and azidation steps. Then, a series of new 1,2,3-triazolylphosphonate were synthesized through the multicomponent alkyne-azide 1,3-dipolar cycloaddition catalyzed by copper nanoparticles on activated carbon. The reactions were carried out in water and at a very low copper loading as green conditions, leading to the triazolylphosphonate products in moderate to good yields. Studies about their activity as butyrylcholinesterase inhibitors are underway.

  • Open access
  • 30 Reads
Development of a Corrosion Protection Silica-based hybrid Sol-gel Coatings on Aluminum Alloys 2024-t3 by Encapsulating Benzimidazole and Octadec-9-enoic acid.
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Corrosion affects any metallic materials, such as pipelines, ships, and offshore platforms, as it is estimated that year’s corrosion losses are one-fifth of the global resources. The most efficient way of reducing the impact of this environment is using coatings- provision of barrier between the material and the aggressive environment. Hybrid Silica-based Sol-gel-derived coating presents one of the most viable pre-treatments alternatives to chromate. A significant advantage of the sol-gel process is the possibility of forming a hybrid inorganic-organic structure network at low temperatures. In addition, sol-gel coatings have good adhesion to metallic substrates and organic materials. Therefore, as a continuance of previous research on sol-gel coating systems. The work reports the performance of hybrid sol-gel formula formed from TEOS and MTMS enhanced by polysiloxanes with and without the presence of environmental benign corrosion inhibitor individually formed from benzimidazole (BZI) and Octadec-9-enoic acid (OA) as a duplex layers coating system. The sol-gel only and the duplex coating systems were at the same thickness, which can be applied to lightweight alloys such as aluminum alloy 2024-t3 to form a fundamentally corrosion inhibited and crack-free coating. The corrosion protection mechanism’s evaluation for these coatings is based on electrochemical tastings using potential-dynamic polarization scanning (PDPS) and electrochemical impedance spectroscopy (EIS). The protective properties of the coating system were studied when immersed in 3.5% NaCl to imitate the aggressive environment. The chemical confirmation was checked by infrared spectroscopy (FTIR), supported by analyzing surface morphology after 360 hrs. of immersion testing using scanning electron microscopy (SEM) and water contact angle for coated samples (WCA). The corrosion resistance performance of this coating system is a result of the combination of good adhesion, and pore blocking of the silica-based hybrid coating, and the presence of both encapsulated OA as a carrier and BZI as a film-forming volatile corrosion inhibitor resulting in durable film-forming, reducing the reaction at cathodic sites. Also, it exhibited excellent anti-corrosion properties, providing an adherent protective film on the aluminum alloy 2024-T3 samples compared to previous sol-gel and bare metals, which might last more than 60 days without any sign of failure, with an eco-friendly and cost-effective.

  • Open access
  • 43 Reads
Synthetic access to tetracationic benzoporphyrins and their role as photosensitizers towards gram-negative Escherichia coli

Nowadays population face an episode where bacteria are becoming resistant to antibiotics, and it is crucial to find out alternatives and new molecules to fight these microorganisms. Photodynamic inactivation of microorganisms has been pointed out as an alternative to conventional therapies. This is an approach that involves the light activation of a photosensitizer which in the presence of molecular oxygen (3O2) leads to the generation of cytotoxic species, namely singlet oxygen (1O2). Among the several photosensitizer agents available, porphyrins and related macrocycles have been highlighted as the most advantageous and effective due to their characteristic photochemical and photophysical features.

This work describes the synthesis and characterization of benzoporphyrins derivatives bearing triazolyl groups and also of the analogues with pyridyl units under Heck coupling conditions. The benzoporphyrin derivatives containing pyridyl groups were further quaternized with iodomethane and 1-iodopentane to evaluate the influence of alkyl chain size on their photoinactivation ability. The biological studies towards Gram-negative bioluminescent Escherichia coli showed that the tetracationic benzoporphyrins can efficiently inactivate this bacterium. However, the pentylated derivative showed to be more efficient in E. coli inactivation when compared to the methylated porphyrin, probably due to its larger alkyl chain, which promotes better bacterial membrane binding.

  • Open access
  • 30 Reads
“TYC” reaction between alkynes and catechol-thiol derivatives promoted by copper nanoparticles: Mechanism study by DFT calculation

In a recently published article by our research group, it was demonstrated that the hydrothiolation of activated alkynes (with electron-withdrawing groups), “TYC” reaction, is a successful way to functionalize thiols bearing catechols. The reaction was promoted by a heterogeneous catalyst composed of copper nanoparticles supported on TiO2, showing regio- and stereoselective towards the anti-Markovnikov Z-vinyl sulfide in most of the cases studied, in good to excellent conversions (47-97%). However, no product was obtained when a deactivated alkyne such as propargylamine was tested, nor when FeNPs/TiO2 was employed as catalyst.

Through DFT studies, the different chemical-interactions between the reagents, the metal and the support were modeled, employing propiolamide and CuNPs/TiO2 as model alkyne and catalyst, respectively. Calculations were made using PBE functional with D3BJ dispersion correction, Def2-TZVP basis set and the CPCM model for the solvent (DCM). DFT studies and experimental data were consistent with a reaction mechanism based on a copper-catalyzed anti-Markovnikov hydrothiolation process leading to the formation of the Z-vinyl sulfide isomer. On the other hand, when FeNPs/TiO2 was used as catalyst for the hydrothiolation reaction, no vinyl sulfide was obtained. Theoretical calculation revealed a decrease in charge distribution mainly at the internal Csp-atom of the acetylenic system. In contrast, for the CuNPs/TiO2 the decrease in charge was mainly observed at the terminal Csp- atom, consequently leading to the anti-Markovnikov product. Besides, the system with propargylamine revealed that the formation of intermediates in the nucleophilic attack was thermodynamically unfavorable, unlike propiolamide, where the formation of intermediates was mainly exothermic.

  • Open access
  • 32 Reads
A new hybrid molecules based on (5Z,9Z)-icosa-5,9-dienoic acid and monocarbonyl derivatives of curcuminoids

Efficient methods for the synthesis of previously undescribed hybrid compounds based on monocarbonyl derivatives of curcumin and 5Z,9Z-dienoic acid with yields of 58-66% was presented. The key monomer, (5Z,9Z)-icosa-5,9-dienoic acid was prepared using the stereoselective cross-cyclomagnesiation reaction of aliphatic and oxygen-containing 1,2-dienes catalyzed by Cp2TiCl2.

  • Open access
  • 42 Reads
Approach to the synthesis of five-membered organophosphorus compounds through alumoles and alumolanes

This work summarizes the results of a new approach to the synthesis of previously undescribed, hard-to-obtained five-membered cyclic organophosphorus compounds - 3-alkyl(aryl)-substituted phospholanes, α,ω-bisphospholanes, polycyclic phospholanes, 4,5-dialkyl(diaryl)-disubstituted 2,3-dihydrophospholes, as well as their oxides and sulfides. Alumolеs and alumolanes synthesized by the reaction of cycloalumination of available unsaturated compounds (terminal alkenes, α,ω-alkadienes, norbornene derivatives, symmetrical internal alkynes) with Et3Al in the presence of a Cp2ZrCl2 catalyst were used as precursors. The substitution of aluminum atoms in cyclic organoaluminum compounds for phosphorus atoms takes place using alkyl(aryl)phosphorus (III) dichlorides. The developed one-pot method of gives the products in high yields under mild conditions.

  • Open access
  • 32 Reads
Designing a phosphino-thiosemicarbazone ligand capable to stabilize coinage metal ions.

Thiosemicarbazones are interesting organic skeletons due to their great coordinative versatility, their interesting biological and pharmacological properties, as well as their structural diversity. However, the isolation of their monovalent metal complexes, such as Cu(I), Ag(I) or Au(I), is a partially studied field, since co-ligands with soft donor atoms such as phosphines, are needed.

In this context, our research group has been studying the design of a new family of ligands capable of stabilising coinage complexes without the need for auxiliary co-ligands. To this end, it was decided to incorporate a phosphorus atom into the structure of a thiosemicarbazone ligand. This work presents the design, synthesis and structural characterisation of a new phosphino-thiosemicarbazone ligand.