STUDIA CHEMIA - Issue no.3 / 2021 - Table of contents

It is my great pleasure to see this special issue dedicated to the memory of Professor Ph.D., Petre Frangopol!

Petre Frangopol was a top Romanian scientist, a member of the Romanian Academy, who, during his rich and productive scientific career, was also associated to our university.

I met him in 2005, when I was the personal adviser for research of the minister for education and research, as a partner/consultant in the research/ education reform we started then. He was among the (few) scientists who supported the excellence, as the main framework of the 2005 reform. Then, we together initiated “the Presidential Commission” – around the cabinet of the President of Romania –, which assessed the Romanian education-research system and then proposed a new strategy in education/research, on which the new law of education was built in 2011. After that, we together initiated and created in 2013 the G3A (Analysis/Attitude/Action), a Think Tank continuing the analysis and the monitoring of 2005/2011 reforms and beyond them; the G3A Think Tank produced several influential reports during the years.

In the process, we started to also collaborate scientifically and we even published some works together, relating policy of science and/or scientometrics (e.g., David & Frangopol, 2015, in “Scientometrics”: The lost paradise, the original sin, and the Dodo bird: A scientometrics Sapere Aude manifesto as a reply to the Leiden manifesto on scientometrics; DOI:10.1007/s11192-015- 1634-2).

In the end, despite the age difference, we became close friends, so his death was not only a professional lost for me and the Romanian academic community, but also a personal one for me!

Thank you, dear colleague and friend, for everything! Your life was inspirational for many of us and you created things, which remains and positively impact many!

Daniel DAVID, Rector of the Babeș-Bolyai University

Petre T. Frangopol (1933-2020). Romanian Academic, Scientist, Mentor and Friend

The Never-Tired Apollonian Petre T. Frangopol, My Dear Friend Petrache

Keywords: sugar beet pulp, drying kinetics, drying rate, mathematical modeling

Petre Frangopol – A Fighter in the Public Arena

Professor Petre T. Frangopol – A Brief, Personal Account on the Legacy He Left in Iaşi

The abundant evidence linking epilepsy with hydroelectrolytical changes in epilepsy reported in the medical literature for over 9 decades is reviewed. Our work on this topic is presented, including the detection by NMR of a decreased water permeability of the red blood cells (RBCs) from children with epilepsy compared with control children. This was interpreted as a generalized membrane defect in epilepsy. The subsequent program of research performed by Gh. Benga’s group in Cluj-Napoca led to the discovery of the first water channel protein (WCP) in the RBC membrane, protein later called aquaporin1 (AQP1). A lot of WCPs (AQPs and relatives) have been identified later by various authors, in the body of humans and many other species. The physiological roles of WCPs from the central nervous system (CNS) and their implications in epilepsy and other neurological diseases are reviewed, including the information published in the last months.

Keywords: water channel proteins, aquaporins, epilepsy, paediatric neurology, NMR

Neuropharmacology (NP), which evolved along with scientific medicine, got treatments for several common disorders of the nervous system. But, most of the NP drugs are just symptomatic, reducing only the manifestations of brain pathologies. Also, for main neuro-psychiatric pathologies (e.g. the neurodegenerative diseases) there is very poor or no medication, and the output of NP drug discovery declined in the last decades. This review paper argues that those drawbacks derive from the reductionist NP leaning towards single–target selective drugs, at odds with the essential complexity of brain functioning and the multifactorial causality of its pathologies. Most active neuro-drugs (e.g. valproate and levetiracetam) are in fact multi-mechanistic since they have been selected by phenotypic screening in vivo, not by single-target binding in vitro. A putative solution of the relative NP stagnation seems to come with the emergent systemic approach of network pharmacology. A plausible flowchart of the main stages of a network NP drug discovery endeavor is finally sketched.

Keywords: brain complexity, systems biology, network pharmacology, magic bullet, magic shotgun, multi-mechanistic drug, valproate, levetiracetam, multi-potent drug, poly-therapy

The magnetic and transport properties of polycrystalline Sr2FeMoO6 perovskites are strongly dependent on their microstructure. A cluster glass type behavior was shown at the grain boundaries. The increase of the sintering time from 4 to 8 hrs in Sr2FeMo1-xWxO6 and Ca1.5La0.5FeMo1- xWxO6 series improves the crystallographic order. As a result there is an increase of both the saturation magnetizations and of spin polarizations.

Keywords: perovskites, magnetic behavior, transport properties

The biocompatibility of uncoated titanium, Ti, nails and coated with an innovative biocomposite is assessed in a rat model of femoral fracture. The biocomposite is based on multi-substituted hydroxyapatite, ms-HAP containing Mg, Zn and Si, and is used as a coating material deposited on Ti implants, due to the excellent biocompatibility and osteoconductive property of ms-HAP. Specific focus has been given to biocomposite coating made of ms-HAP functionalized with collagen (ms-HAP/COL, core/shell nanoparticles) NPs embedded into poly lactic acid, PLA, matrix and finally covered by COL layer. This coating on Ti implants is noted as ms-HAP/COL@PLA/COL and named HAPc, and is characterized by SEM images and EDX spectra. Twenty-four Wistar albino rats with left femoral fracture, were used and divided in two equal groups, namely the control group, CG, with uncoated Ti implants and HAPc rat group with Ti implants coated with HAPc biocomposite through layer-by-layer, LBL, dip coating technique. After two- and eight-weeks postsurgery, they were evaluated by bone markers serum concentration, micro-CT and histological study. The alkaline phosphatase (ALP) and osteocalcin (OCN) expression, in the HAPc group showed higher values with an osteoblastic activity more intense and a more advanced callus stage. The micro-CT results showed that biocomposite coating significantly increased the bone volume/ tissue volume (BV/TV). The most advanced stage of bone remodelling with osseointegration of the Ti implants was observed in HAPc group, where the new formed trabecular bone is almost completely replaced by compact bone. This study provides a novel strategy for the treatment of bone fracture with a superior osseointegration of biocomposite coated Ti implants and potential orthopaedic applications.

Keywords: biocompatibility, titanium implants, biocomposite coating, multisubstituted hydroxyapatite, PLA, collagen

Plants produce thousands of phenolic and polyphenolic compounds as secondary metabolites. They are essential to the physiology of plants being involved in diverse functions such as lignification and structure, pigmentation, pollination, allelopathy, pathogen and predator resistance and growth. Approximately 8000 have been described to date, major classes being flavonoids, flavones, flavan-3ols, flavanones and anthocyanins. They can be isolated from biomass waste and cultivated and spontaneous plants by biorefining and used for their biological properties in different fields. In this paper some examples of uses such as: modulation agents of carbohydrates metabolism in diabetes and alcoholic fermentation, agents for regulation of physiological process in plants (germination, plant propagation and cultivation, tissue culture, bioremediation), modulation agents of metabolic processes in microorganisms (antifungal and antibacterial properties, antioxidants), models to study the influence of stress factors (hydrogen peroxide oxidation and UV irradiation and life span regulation), and carbon sources as substrates in medium cultivation of microorganisms, are presented.

Keywords: polyphenols, sources, isolation and characterization, biological properties

A complex analysis on the photovoltaic capabilities of two triarylamine-thienyl-based donors was conducted using different buffer layers in the structure of the cells, such as ZnO and MoO3. The photovoltaic properties of the fabricated cells were characterized under simulated solar light, and monochromatic illumination. The analysis revealed a higher power conversion efficiency for the inverted-bulk-heterojunction structures.

Keywords: Organic solar cells, bilayer structure, bulk heterojunction, inverted structure, triarylamine derivatives/p>

Molecular dynamics simulations were employed in order to analyze the interfacial interaction of polylactic acids with zirconia and hydroxyapatite surfaces. The interactions of polymers on five crystallographic planes were simulated. Silane coupling agents can improve the interactions between the bioceramic surfaces and the polylactic acids. The effects of the coupling agents are more evident in the presence of hydroxyapatite surfaces. Weak interactions hold together the polylactic acids and bioceramic systems. These interactions are formed between the hydrogen atoms from methyl groups or from the main chains of the polylactic acids and the oxygens of the surfaces. Polylactic acids change their conformations after molecular dynamics simulations due to the interactions. The conformation changes are more obvious when silane coupling agents are added to the polylactic acids and bioceramic systems.

Keywords: polylactic acid, hydroxyapatite, zirconia, molecular dynamics, weak interactions

Acid-sensing ion channel (ASIC) is involved in important processes like synaptic plasticity and learning, fear and anxiety, pain sensation. Due to its role in neurodegeneration and neuroinflammation, the channel is a viable pharmacological target. The channel is activated by acid pH pulses and it rapidly desensitizes; therefore the channel can exist in open, closed and desensitized states. Here we performed a molecular docking study of some ASIC1 ligands like amiloride, cocaine, histamine, ibuprofen, sinomenine and Zn2+ in the transmembrane region of ASIC1 channel models in different states (closed, open and desensitized). Also, since channel properties are influenced by Ca2+, we performed a set of calculations when Ca2+ is present in the channel pore. In addition, we modelled mutant channels in different states with substitutions of residues forming Ca2+ binding sites. The interaction of ligands with mutant channel models was investigated in the presence and absence of Ca2+. Our results show an affinity of ASIC1 for ibuprofen, followed by Zn2+, histamine and amiloride. Sinomenine and cocaine do not appear as ASIC1 ligands regardless of channel state. Overall, Ca2+ enhances the interactions of ligands with the channels, including the interactions of cocaine that is not recognized as an ASIC1 ligand. The effect of mutations is to reduce the favourable interactions with ligands. The results obtained on the three channel states are consistent, showing that results are not significantly influenced by the choice of model. Our results bring new information on ASIC1 pharmacological modulation by showing that Ca2+ presence in the pore enhances channel affinity for ligands.

Keywords: ASIC1, molecular docking, protein-ligand interaction, pharmacology

Titanium implants are highly resistant to external forces and have affordable prices but the contact between Ti metal and surrounding native tissue could provoke an immunological response. The developing of biomimetic coating onto the Ti surface proves to be a smart choice to enhance the osseointegration and ensure an optimal healing process, due to the creation of nanostructured biomaterials like those in native bone. Thus, we designed a composite coating based on multi-substituted hydroxyapatite (noted ms-HAP or HAPc) nanoparticles, NPs, doped with essential elements: Mg, Zn and Si, functionalized with collagen type 1 (COL), embedded into poly lactic acid, PLA, matrix, and finally covered with COL layer to achieve biomimetic structures. Thin layers of biomimetic composite were self-assembled onto Ti surface via dip-coating method. Both, initial and coated Ti implants were investigated by atomic force microscopy (AFM), which allows surface investigation at high resolution of nano-level. COL amount in composite might self-assemble as COL fibers assuring a biomimetic structure, characterized by important features, like suitable porosity to facilitate the delivery of nutrients to osteoblasts and proper nano-topography and surface roughness to promote cell adhesion and proliferation. The outermost layer is of pure collagen which could assure a natural attachment to the bone tissue promoting osseo-integration.

Keywords: biomimetic structure, bio-composite, multi-substituted hydroxyapatite, collagen, PLA, AFM images, surface roughness

Single-molecule electrophysiology techniques using proteinbased or solid-state nanopores as nanoreactors were proven incredibly useful as platforms for sensing and biophysical characterisation of biological molecules (e.g., peptides, proteins), DNA detection and sequencing in a label-free, low-cost, rapid and high signal-to-noise ratio manner. Herein we present a number of discoveries in this field, developed over the years in our laboratory, including: (i) the pH-mediated, fine-tuning of peptides passage through the α-hemolysin nanopore; (ii) increase of the capture rate and dwell times of polypeptides inside the nanopore, through engineering dipole-like polypeptides; (iii) the implication of a nanopore-AuNP (citrate anion-coated gold nanoparticles) platform to selectively detect nanomolar concentrations of target ssDNA.

Keywords: single-molecule, peptides, electrophysiology, detection, sensing, nanopore, DNA, PNA

The mercury(II) complexes [Hg(SCN)2{PPh[C6H4(CH2NMe2)-2]2}] (1) and [2,6-(Me2NCH2)2C6H3Se][HgCl3] (3) were prepared and structurally characterized in solution by multinuclear NMR and ESI mass spectrometry. The reactions performed to obtain the complex [2,6-(Me2NCH2)2C6H3SeHgCl] (2) failed and we could isolate only a mixture of 3 and [(HgCl2)3{2,6-(Me2NCH2)2C6H3}] (4). Compounds 1 and 4 were characterized by single-crystal X-ray diffraction.

Keywords: mercury(II) complexes, triarylphosphane, organoselenium ligand; intramolecular coordination; solution behavior, solid state structure.

Raman microspectroscopy was tested as an alternative/ complementary method for biochemical evaluation of the synaptosomes obtained from neonatal rat brain prenatally exposed to sodium valproate and treated with allicin. Spectrophotometric assays of several oxidative stress markers (catalase, superoxide dismutase, total thiols) and acetylcholine esterase activity revealed the redox balancing function and pro-cholinergic effect of the allicin as compared to the valproate effect. Raman evaluation showed no significant changes in our experimental conditions. Different concentrations and volumes of the synaptosomes vesicles must be tested for the optimal Raman examination of these purified synaptosomes.

Keywords: Raman, synaptosomes, brain, vesicles, sensitive method, redox status

In this study, the ions release of physiological elements from pure stoichiometric hydroxyapatite, HAP, and from multi-substituted hydroxyapatite, ms-HAPs, containing 1.5%Mg, 0.2%Zn, 0.2%Si and 5 %Sr, noted HAPc-5%Sr, and from HAPc-10%Sr, in water and in simulated body fluid, SBF, was studied by inductively coupled plasma optical emission spectrometry, ICP-OES, both in static and simulated dynamic regimes. The HAP and ms-HAP nanoparticles, NPs, were prepared by wet chemical precipitation and lyophilized powders were physicochemical characterized as presented elsewhere. The in vitro cations and anions release mechanism was investigated by applying a modified Higuchi model, which fits well the experimental results, particularly for simulated dynamic conditions. The predominant role of diffusion in the release of ions from the hydroxyapatites was confirmed. The sustained ions release from these nanomaterials recommends the investigated ms-HAPs for therapeutic applications.

Keywords: multi-substituted hydroxyapatites; ions release; static conditions, simulated dynamic conditions; Higuchi model

The solid dispersion system containing a high amount of the natural compound curcumin was prepared with whey protein concentrate by spray-drying method in 5:1 molar ratio. X-ray powder diffraction and DSC techniques show the formation of the solid dispersion system in amorphous state, and the presence of weak hydrogen bond type interactions between the components was established by FTIR analysis. SEM images show highly homogeneous donut-like spherical microparticles morphology for the system. The solubility of curcumin from the system was enhanced compared to practically insoluble raw curcumin, reaching a value of 70 μg/mL in aqueous buffer solution at pH=8 similar with intestinal environment. The synthesized material had better effects against skin melanoma cells, compared to lung adenocarcinoma cells, but in both cases the effect was promising, and through further and more complex analyses the antitumoral potential of CUC-WPC_SD could be exploited.

Keywords: curcumin, whey protein concentrate, complexation, enhanced solubility, anticarcinogenic effect

The old wooden church from Dragu, Sălaj County, was built on the hill of Dragu village between 1806 and 1809, according to the inscription found inside. The investigations targeted the imperial gates (the main entry from the nave to the altar used by the priest during church service and adorned with painted icons and elaborated wood sculpture) and aimed to identify the materials used for their manufacture: the wood species, pigments, ground, binders. For the identification of materials two spectroscopic methods were employed: XRF (X-ray fluorescence) and FTIR (Fourier transform IR absorption). The employed materials are: linden wood for the imperial gates, gypsum for ground; lead white, Prussian blue, gold and silver leaf, iron red, lead red, cinnabar, realgar, orpiment, Scheele’s green for pigments; egg yolk and bone glue as binders.

Keywords: XRF - non-destructive spectroscopy, FTIR absorption destructive spectroscopy, wooden church, imperial gates, painting materials, pigments

Several relaxation pathways of the low-lying electronic excited state dynamics for acetophenone including also the singlet-triplet intersystem crossings were studied. The multireference Hartree-Fock and second order perturbation theory methods together with def2-tzvp basis set were used to characterize the equilibrium geometries and the crossing points between different potential energy surfaces (PES) up to the third excited state level considering both the singlet and triplet spin states. The electronic deactivation pathways studies reveal that the acetophenone shows several possible deactivation channels but their occurring probability strongly depends on the local profile of the PES of the intermediate states.

Keywords: acetophenone, conical intersection, intersystem crossing, spinorbit coupling, deactivation pathway

The paper reports the AMS (accelerator mass spectrometry) radiocarbon dating results of the large pedunculate oak of Mercheaşa, Romania, which has a circumference of 10.16 m. Two wood samples were extracted from the trunk and from the largest horizontal branch. Five segments from these samples were analysed by AMS radiocarbon. The oldest dated sample segment originates from the largest horizontal branch, very close to its geometrical centre. It had a radiocarbon date of 386 ± 45 BP, which corresponds to a calibrated age of 540 ± 35 calendar years. This value indicates an age of 560 ± 35 years for the oak of Mercheaşa.

Keywords: AMS radiocarbon dating, Quercus robur, dendrochronology, age determination, Romania