Publications

Abstract The multifaceted nature of the neurodegenerative diseases, as Alzheimer's disease (AD) and Parkinson's disease (PD) with several interconnected etiologies, and the absence of effective drugs, led herein to the development and study of a series of multi-target directed ligands (MTDLs). The developed RIV-IND hybrids, derived from the conjugation of an approved anti-AD drug, rivastigmine (RIV), with melatonin analogues, namely indole (IND) derivatives, revealed multifunctional properties, by associating the cholinesterase inhibition of the RIV drug with antioxidant activity, biometal (Cu(II), Zn(II), Fe(III)) chelation properties, inhibition of amyloid-/3 (A/3) aggregation (self- and Cu-induced) and of monoamine oxidases (MAOs), as well as neuroprotection capacity in cell models of AD and PD. In particular, two hybrids with hydroxyl-substituted indoles ( 5a2 and 5a3) ) could be promising multifunctional compounds that inspire further development of novel anti-neurodegenerative drugs.

Abstract An experimental and computational thermochemical study is reported focus on the relationship between the energetic properties, the structural characteristics and the inherent reactivity of three thiothiadiazoles: 2-amino5-(methylthio-)-1,3,4-thiadiazole, 2-amino-5-(ethylthio-)-1,3,4-thiadiazole and 2-mercapto-5-methylthio-1,3,4thiadiazole. From the DSC measurements, the enthalpies of fusion and the respective onset temperatures were determined. The standard molar energies of combustion of the (alkylthio)-1,3,4-thiadiazoles were determined by rotating bomb combustion calorimetry. The corresponding standard molar enthalpies of sublimation, at T = 298.15 K, were derived from high-temperature Calvet microcalorimetry measurements and the study of the dependence of the compound's vapour pressures with the temperature, using the Knudsen-effusion technique. The combination of these experimental results enables the calculation of the standard molar enthalpies of formation in the gaseous state, at T = 298.15 K, which are discussed in terms of structural contributions. The latter property was also determined from high-level ab initio molecular orbital calculations at the G3(MP2)//B3LYP level of theory. The computed values are in good agreement with the experimental ones. In addition, a conformational and tautomeric study was conducted using the same approach, in order to provide insight on the amino/imino and thiol/thione tautomerism of the compounds studied. The amino form predominates in aminothiadiazoles, while the thione form prevails in mercaptothiadiazole. Moreover, the relative thermodynamic stability of each compound was also evaluated showing that in both solid and gas phases, the most stable species is the mercaptothiadiazole (in its thione form). The thermochemical results of the (alkylthio)-1,3,4-thiadiazoles show a good agreement with the NBO (natural bond orbitals) analysis results.

Abstract Given the challenges associated with understanding electrochemistry content by engaging in prediction, observation, and explanation, laboratory activities can foster active participation and critical thinking, enabling individuals to proactively confront and revise their understanding. Since pre-service teachers should gain firsthand experience with predict-observe-based on a predict-observe-explain strategy, we propose a laboratory activity presented as a mystery box related to concentration cells coupled with an Arduino-based electronic data measurement system to identify how pre-service chemistry teachers move from observations to inferences in a qualitative research. Data was collected by written records and oral explanations during the practical interactions. Results suggest that the proposed laboratory activity allows pre-service chemistry teachers to access data and correct inferences related to electrochemistry content, promoting critical thinking. Data also showed a connection between the macroscopic and symbolic domains, and pre-service teachers recognized concepts associated with the activity, such as solution conductivity and the potential difference in chemical reactions, interpreting the system with prior knowledge, like electron flow direction and concentration cell components. However, additional strategies are needed for detailed and consistent observation and inference recording, enhancing the potential of such activities in favoring electrochemistry education in high schools.

Abstract Iron is essential for the formation, maturation and dispersal of bacterial biofilms, playing a crucial role in the physiological and metabolic functions of bacteria as well as in the regulation of virulence. Limited availability of iron can impair the formation of robust biofilms by altering cellular motility, hydrophobicity and protein composition of the bacterial surface. In this study, the antibiofilm activity of two natural iron chelating agents, kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) and maltol (3-hydroxy-2-methyl-4-pyrone), were investigated against Staphylococcus aureus and Pseudomonas aeruginosa. In addition, the ability of these 2-hydroxy-4-pyrone derivatives in preventing and eradicating S. aureus and P. aeruginosa biofilms through the enhancement of the efficacy of two antibiotics (tobramycin and ciprofloxacin) was explored. The iron binding capacity of the kojic acid and maltol was confirmed by their affinity for iron (III) which was found to be about 90 %, comparable to the regular chelating agent ethylenediaminetetraacetic acid (EDTA, 89 %). The antibiofilm efficacy of 2-hydroxy-4-pyrone derivatives, alone and in combination with antibiotics, was evaluated by measuring the total biomass, metabolic activity, and culturability of biofilm cells. Furthermore, their impact on the membrane integrity of S. aureus biofilm cells was investigated using flow cytometry and epifluorescence microscopy with propidium iodide staining. It was also examined the ability of 2-hydroxy-4-pyrone derivatives and 2-hydroxy-4-pyrone derivate-antibiotic dual-combinations in inhibiting the production of virulence factors (total proteases, lipases, gelatinases and siderophores) by S. aureus. Regarding biofilm formation, the results showed that 2-hydroxy-4-pyrone derivatives alone reduced the metabolic activity of S. aureus biofilm cells by over 40 %. When combined with tobramycin, a 2-log (CFU cm-2) reduction in S. aureus biofilm cells was observed. Moreover, the combination of maltol and kojic acid with ciprofloxacin prevented P. aeruginosa biomass production by 60 %, compared to 36 % with ciprofloxacin alone. In pre-established S. aureus and P. aeruginosa biofilms, selected compounds reduced the metabolic activity by over 75 %, and a 3-log (CFU cm-2) reduction in the culturability of biofilm cells was noted when kojic acid and maltol were combined with antibiotics. Moreover, 2-hydroxy-4-pyrone derivatives alone and in combination with tobramycin, damaged the cell membranes of pre-established biofilms and completely inhibited total proteases production. Despite the increasing of reactive oxygen species production caused by the cellular treatment of maltol, both 2-hydroxy-4-pyrone derivatives showed good safe profile when tested in human hepatocarcinoma (HepG2) cells. The pre-treatment of HepG2 cells with both compounds was crucial to prevent the cellular damage caused by iron (III). This study demonstrates for the first time that the selected 2-hydroxy-4-pyrone derivatives significantly enhance the antibiofilm activity of tested antibiotics against S. aureus and P. aeruginosa, highlighting their potential as antibiotic adjuvants in preventing and eradicating biofilm-related infections.

Abstract An extensive thermochemical study of gamma-undecanolactone and delta-undecanolactone has been developed using two complementary calorimetric techniques. The combustion energy of each compound was determined by static-bomb combustion calorimetry, and the corresponding enthalpy of vaporization was determined by high-temperature Calvet microcalorimetry, in which both properties of each compound are reported at T = 298.15 K. The standard molar enthalpy of formation in the gas phase of each lactone was derived by the combination of the experimental results. Additionally, high-level computational calculations were carried out, using composite ab initio G4 and G4(MP2) methods, as well as DFT M06-2X/6-311++G(d,p) approach, to estimate the corresponding enthalpy of formation in the gas phase. The experimental and computational results are in good agreement. The G4 and G4(MP2) methods show the best accordance with experimentally determined gas phase enthalpies of formation. The experimental results are discussed in terms of structural contributions to the energetic properties of the lactones studied, as well as to other alkylated gamma- and delta-lactones, and empirical correlations are suggested for the estimation of the standard molar enthalpies of formation, at T = 298.15 K, for other alkylated gamma- and delta-lactones, both in the liquid and gaseous phases, as well as for the respective enthalpies of vaporization. Finally, the thermochemistry of individual steps of lactone ring opening and successive decarboxylation mechanism, including the identification of transition states, was studied using the M06-2X/6-311++G(d,p) approach.

Abstract Borophene, a monolayer of boron atoms, belongs to intensively studied two-dimensional beyond-graphene materials. The B36 borophene nanoflake is a finite size model system, containing a hexagonal vacancy similar to the ones present in (312 and chi 3 borophene sheets. The hydrogen binding performance of B36 decorated with various transition metal atoms is investigated using density functional theory and quantum theory of atoms in molecules. Hydrogen is considered to become one of the crucial energy sources in future, hence, a search for effective hydrogen storage materials is of urge importance. Obtained results suggest that B36 decorated with Co, Ni, Fe, and Cu possess strong affinity to bind the H2 molecule via formation of eta 2-dihydrogen bonds. Among them, the strongest H2 binding is found for Co- and Ni-decorated B36. Furthermore, B36 decorated with Sc and Ti behave like H-H bond breakers while B36 decorated with Zn possess only negligible affinity to bind H2 molecule. The stability of the B36 decorated with Co and Ni is verified by ab initio molecular dynamics. The presented data may also serve as a basis for reference in future large-scale computational studies of borophene-based materials.

Abstract Heat capacity, a crucial physical property for chemical processes, is often understudied in Deep Eutectic Solvents (DESs), which in turn are promising green alternatives to environmentally hazardous conventional solvents. This work addresses this gap by developing a machine learning model to predict DES heat capacity and identify key structural features influencing it. We employed a dataset of 530 DESs with corresponding experimental heat capacity values. Quantum-chemical COSMO-RS-based descriptors, capturing detailed information about DES structures, were calculated for each data point. Various machine learning algorithms, namely k-Nearest Neighbours (kNN), Random Forests (RF), Neural Network Multilayer Perceptron (MLP), and Support Vector Machines (SVM) were explored alongside a linear model (Multiple Linear Regression, MLR). Hyperparameter optimisation ensured all models were fine-tuned for optimal performance. The most successful model, based on the MLP technique, achieved remarkably low Average Absolute Relative Deviation (AARD) values of 0.500 % and 3.999 % for the training and test sets, respectively. This signifies a significant improvement in prediction accuracy compared to traditional methods. Furthermore, by applying a SHapley Additive exPlanations (SHAP) analysis, we identified the most crucial structural factors within DES components that govern their heat capacity. This comprehensive investigation offers valuable insights that can pave the way for an efficient design of novel DESs in the future. © 2024 The Author(s)

Abstract The development of simple, selective, and cost-effective methods for quantification of bovine serum albumin (BSA) is currently very important for assessing milk quality (and safety). In this work, a new surface plasmon resonance (SPR) sensor was developed, consisting of imprinted hydrogel-based nanoparticles (nanoMIPs) immobilized on gold platforms, to quantify BSA in bovine milk. The nanoMIPs prepared for recognition of BSA were synthesized by the precipitation polymerization approach, using a synthetic BSA epitope (VVSTQTALA) as template. The spherical MIP nanoparticles (NPs) had an average size of 60 nm. The binding studies performed revealed that the binding affinity of the prepared nanoMIPs to BSA (KD = 7.1 × 10−6 mol L−1) was comparable to that obtained by a natural BSA antibody (KD = 2.5 × 10−6 mol L−1). The plasmonic sensor incorporating the MIP nanomaterials achieved a limit of detection (LOD) of 1.02 × 10−6 mol L−1 (0.068 mg mL−1) and a limit of quantification (LOQ) of 3.39 × 10−6 mol L−1 (0.225 mg mL−1), over a linear range from 2.0 × 10−6 mol L−1 to 1.5 × 10−5 mol L−1. Moreover, the selectivity studies revealed a significant sensor response towards casein and a negligible response towards vancomycin. In the end, the optical sensor was tested against commercial milk samples, showing promising viability for detection of BSA as the value reported by the plasmonic sensor ((1.0 ± 0.1) × 10−4 mol L−1) was very close to that obtained by size exclusion-high-performance liquid chromatography (SEC-HPLC). © 2025 The Author(s)

Abstract The lower refractive index sensitivity (RIS) of plasmonic nanoparticles (NP) in comparison to their plasmonic thin films counterparts hindered their wide adoption for wavelength-based sensor designs, wasting the NP characteristic field locality. In this context, high aspect-ratio colloidal core-shell Ag@Au nanorods (NRs) are demonstrated to operate effectively at telecommunication wavelengths, showing RIS of 1720 nm/RIU at 1350 nm (O-band) and 2325 nm/RIU at 1550 nm (L-band), representing a five-fold improvement compared to similar Au NRs operating at equivalent wavelengths. Also, these NRs combine the superior optical performance of Ag with the Au chemical stability and biocompatibility. Next, using a side-polished optical fiber, we detected glyphosate, achieving a detection limit improvement from 724 to 85 mg/L by shifting from the O to the C/L optical bands. This work combines the significant scalability and cost-effective advantages of colloidal NPs with enhanced RIS, showing a promising approach suitable for both point-of-care and long-range sensing applications at superior performance than comparable thin film-based sensors in either environmental monitoring and other fields.