Goran Nikolić

Fourier-Transform IR spectroscopic investigations of Cobalt(II)–dextran complexes by using D2O isotopic exchange

Co(II) ion complexes with reduced low-molar dextran (RLMD) derivatives Mw= 5000 − 6000 g/mol, their FTIR spectroscopic characterization, as well as the spectra-structure correlation was investigated in this work. The samples of Co(II) ion complexes with RLMD were deuterated (D2O, Merck) for 2 h, at room temperature, in vacuum. FTIR spectra as an average of 40 scans were recorded at room temperature in the range 4000 – 400 cm−1. FTIR investigation of Co(II)–RLMD complexes by D2O isotopic exchange proved to be a very sensitive method for determining OH group coordination and is related to the hydrogen bond strength. The results of our investigation point to the dextran and their complexes with Co(II) ion are crystalline hydrate molecules. The correlation of physicochemical, spectrophotometric and spectroscopic investigations of these complexes, coordination chemistry of Co(II) ion and the structure of an exopolysaccharide chain are proposed different model structures of the synthesized Co(II) complexes.

Instrumental methods and techniques for structural and physicochemical characterization of biomaterials and bone tissue: A review

A review of recent advances in instrumental methods and techniques for structural and physicochemical characterization of biomaterials and bone tissue is presented in this paper. In recent years, biomaterials attracted great attention primarily because of the wide range of biomedical applications. This paper focuses on the practical aspects of instrumental methods and techniques that were most often applied (X-ray methods, vibrational spectroscopy (IR and Raman), magnetic-resonance spectroscopy (NMR and ESR), mass spectrometry (MS), atomic absorption spectrometry (AAS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES), thermogravimetry (TG), differential thermal analysis (DTA) and differential scanning calorimetry (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM)) in the structural investigation and physicochemical characterization of biomaterials and bone tissue. The application of some other physicochemical methods was also discussed. Hands-on information is provided about these valuable research tools, emphasizing practical aspects such as typical measurement conditions, their limitations and advantages, interpretation of results and practical applications.

Monte Carlo Method Based QSAR Modeling of Coumarin Derivates as Potent HIV‐1 Integrase Inhibitors and Molecular Docking Studies of Selected 4‐phenyl Hydroxycoumarins

Summary In search for new and promising coumarin compounds as HIV-1 integrase inhibitors, chemoinformatic methods like quantitative structure-activity relationships (QSAR) modeling and molecular docking have an important role since they can predict desired activity and propose molecule binding to enzyme. The aim of this study was building of QSAR models for coumarin derivatives as HIV-1 integrase inhibitors with the application of Monte Carlo method. SMILES notation was used to represent the molecular structure and for defining optimal SMILES-based descriptors. Molecular docking into rigid enzyme active site with flexible molecule was performed. Computational results indicated that this approach can satisfactorily predict the desired activity with very good statistical significance. For best built model statistical parameters were: a) 3’ Processing activity: R2=0.9980 and Q2=0.9977 for training set and R2=0.9788 for test set and b) Integration activity: R2=0.9999 and Q2=0.9998 for training set and R2= 0.9213 for test set. Built QSAR models were applied to selected 4-phenyl hydroxycoumarins for calculating desired activity and for HIV-1 integrase inhibition estimation. Additionally, molecular docking study was performed to a newly identified pocket in the HIV-1 integrase enzyme structure for determination of selected 4-phenyl hydroxycoumarins binding mode. Monte Carlo method proved to be an efficient approach to build up a robust model for estimating HIV-1 integrase inhibition of coumarin compounds. Based on QSAR and molecular docking studies, 4-phenyl hydroxycoumarins can be considered as promising model compounds for developing new HIV-1 integrase inhibitors.

Circulating nucleic acids as possible damage-associated molecular patterns in different stages of renal failure

Chronic renal failure (CRF) is a condition associated with the risk of cardiovascular complications. Systemic inflammatory response, initiated by the pathogen-associated molecular-pattern (PAMP) molecules, exerts many similarities with the damage-associated molecular-pattern (DAMP) molecule-induced systemic response. Up to now, a number of DAMP molecules were identified. We hypothesized that the available circulating nucleic acids, acting as DAMPs, may modulate immunoinflammatory reaction in CRF. Patients with the different stages of chronic kidney disease, kidney transplantation, and patients on dialysis were included in the study. Obtained results about higher concentration of circulating ribonucleic acid (RNA), according to the stages of kidney diseases, may contribute to the hypothesis that damaged kidney tissue releases nucleic acids. Circulating RNAs expressed maximal absorbance peak at 270 nm in spectrophotometric scan analysis, which corresponded to polyC, compared to different standard samples. During in vitro conditions, by using the culture of human residential macrophages, circulating RNA isolated from patients with IV–V-stage renal diseases, patients on hemodialysis, and patients who underwent renal transplantation were able to significantly change signal transduction proteins related to inflammation and antiviral response. They significantly increased the intracellular concentration of active nuclear transcription factor nuclear factor kappa B (NF-κB), interferon regulatory factors (IRF)-3, and IRF-7 and significantly decreased melanoma differentiation-associated protein-5 (MDA-5) and p38. In this way, it seems that circulating RNA, acting as DAMP, may contribute to the mechanisms of additional inflammatory reaction, possible immune destruction, and decreased antiviral response, related to complications in kidney diseases.

Circulating Ribonucleic Acids and Metabolic Stress Parameters May Reflect Progression of Autoimmune or Inflammatory Conditions in Juvenile Type 1 Diabetes

The sensing of ribonucleic acids (RNAs) by the monocyte/macrophage system occurs through the TLR7/8 Toll-like receptor family, the retinoic acidi–nducible protein I (RIG-I), and the melanoma differentiation–associated protein-5 (MDA-5). The aim of the present study was to evaluate the effect of circulating RNAs, isolated from juvenile type 1 diabetic patients and healthy control children, on the inflammatory, apoptotic, and antiviral response in human peripheral blood mononuclear cells (PBMCs) isolated from a healthy donor. Obtained effects were compared to the effects of metabolic stress parameters (hyperglycemia, oxidative and nitrosative stress). Forty-eight patients with juvenile type 1 diabetes and control children were included in the study. By performing the chromatographic analysis of circulating RNAs, the peak at the retention time 0.645 min for diabetic and control RNA samples was identified. To determine whether circulating RNAs have an agonistic or antagonistic effect on the signaling pathways involved in inflammatory, apoptotic, and antiviral cascade, their effect on TLR8, RIG-I, MDA-5, MyD88, NF-κB, IRF-3, phosphoIRF-3, IRF-7, RIP, and p38 was evaluated. A significantly lower level was achieved by cultivating PBMCs with circulating RNAs isolated from type 1 diabetic children, compared to the intact PBMCs, in relation to TLR-8, MDA-5, NF-κB, phospho IRF-3, and RIP, while it was higher for Bax. All the metabolic stress conditions up-regulated NF-κB, Bcl-2, and Bax. The NF-κB, determination seems to be the most sensitive parameter that may reflect disease processes associated with the progression of autoimmune or inflammatory conditions, while the IRF3/phosphoIRF3 ratio may suggest an insufficient antiviral response.

Spectroscopic Characterization of Cobalt (II) Complexes with Reduced Low-Molar Dextran Derivatives

Summary The formation of Co(II) ion complexes with reduced low-molar dextran (RLMD, Mw 5000 g/mol) was studied at the pH range from 7.0 to 13.5. The cobalt content in synthesized Co(II)-RLMD complexes was ~3–12% (AAS) and it generally increases with pH. Co(II)-RLMD complexes were characterized by UV-Vis spectrophotometry and FTIR spectroscopy. UV-Vis data for synthesized complexes indicate tetragonally distorted Oh coordination of Co(II) ions with O atoms from ligand. The presence of IR bands at 765 cm−1 and 910 cm−1 in Co(II)-RLMD complexes indicates the existence of α-(1→6)O-glycosidic bonds. The similarities in the γ(C–H) range of the IR spectra indicate that there is no difference in the conformation of the glucopyranose units in RLMD and Co(II)-RLMD complexes. The occurrence of water molecules in Co(II)-RLMD complexes was confirmed by FTIR spectroscopy of deuterated samples.

The Influence of Mg(II) and Ca(II) Ions on Rutin Autoxidation in Weakly Alkaline Aqueous Solutions

Summary Rutin (quercetin-3-O-rutinoside) is one of the most abundant bioflavonoids with various biological and pharmacological activities. Considering the ubiquitous presence of Mg(II) and Ca(II) ions in biological systems we decided to investigate their influence on the autoxidation of rutin in weakly alkaline aqueous solutions. Changes in UV-Vis spectra recorded during the rutin autoxidation in aqueous solution at pH 8.4 revealed that this process was very slow in the absence of metal ions. The presence of Mg(II) and, especially Ca(II) ion, increased the transformation rate of rutin. UV-Vis spectra recorded after prolonged autoxidation indicated the formation of humic acidlike products in the presence of Mg(II) and Ca(II) ions. Four new compounds formed during the initial stage of rutin autoxidation in the presence of Mg(II) and Ca(II) ions were detected by HPLCDAD. Based on the analysis of their DAD UV-Vis spectra and comparison of their retention times with the retention time value for rutin, we concluded that the initial rutin transformation products were formed by the water addition on double bond in ring C and hydroxylation of ring B. A very small decrease of the initial rutin concentration (4%) was observed by HPLC-DAD in the absence of metal ions for the period of 90 minutes. However, rutin concentration decrease was much larger in the presence of Mg(II) and Ca(II) ions (14% and 24%, respectively). The more pronounced effect of Ca(II) ion on the rutin autoxidation may be explained by the stronger binding of Mg(II) ion to rutin and thus greater stabilizing effect on reaction intermediates caused by its higher ionic potential (charge/ionic radius ratio) in comparison to Ca(II) ion. The results of this study may contribute to the better understanding of interactions of Mg(II) and Ca(II) ions with natural phenolic antioxidants which are important for their various biological activities.

The study of the influence of Mg(II) and Ca(II) ions on caffeic acid autoxidation in weakly alkaline aqueous solution using MCR-ALS analysis of spectrophotometric data

UV-Visible spectrophotometry was used to study the influence of Mg(II) and Ca(II) ions on caffeic acid (CA) autoxidation in weakly alkaline aqueous solution. While the autoxidation rate was very slow in the absence of metal ions, both Mg(II) and Ca(II) ions greatly enhanced the autoxidation rate. Determination of the spectral and concentration profiles of the individual components involved in the CA autoxidation processes in the presence of metal ions was performed using multivariate curve resolution-alternating least squares (MCR-ALS) analysis of spectrophotometric data. MCR-ALS analysis supported by the quantum chemical calculations of electronic absorption spectra for possible initial reaction products showed that CA autoxidation in the presence of Mg(II) and Ca(II) ions proceeds by the instant formation of CA–metal complexes followed by the almost simultaneous formation of CA quinone anions and various CA dimers and the final transformation into polymeric, humic acid-like, products. Also, the MCR-ALS analysis revealed that the effect of Mg(II) ions was more pronounced at the initial stage of autoxidation. The differences in the influence of Mg(II) and Ca(II) ions on the CA autoxidation may be attributed to the stronger metal ion–ligand interaction for Mg(II) ions caused by their larger ionic potential in comparison to Ca(II) ions. The results of this study may be important for better understanding of the interactions of Mg(II) and Ca(II) ions with natural phenolic food antioxidants and thus significant for understanding their activities in real systems and optimization of conditions for the processing and/or storage of certain types of foods.

Synthesis, spectroscopic and structural characterization of Co(II)-pullulan complexes by UV-Vis, ATR-FTIR, MALDI-TOF/TOF MS and XRD

Complexes of Co(II) ion with reduced low-molar pullulan (RLMP) (Mw 6000 g/mol) were synthesized in aqueous solutions at boiling temperature in the pH range from 7.5 to 13.5. Obtained Co(II)-RLMP complexes, with cobalt content ∼2-8% (AAS), were characterized by UV-Vis spectrophotometry, FTIR spectroscopy (ATR-FTIR, FT-IRIS), MALDI-TOF/TOF MS, and XRD. Tetragonally distorted Oh coordination of Co(II) ions with O ligand atoms in synthesized complexes is suggested based on the spectrophotometric data. No influence of complexation process on the 4C1 chair conformation of the d-glucopyranose units of pullulan was detected by ATR-FTIR measurements and FT-IRIS showed high homogeneity of synthesized complexes. Some additional depolymerization of pullulan during complex synthesis was indicated by MALDI-TOF/TOF MS but it also revealed good stability of complexes with much weaker binding of Co(II) ion in low molar mass fragments. Even in complexes with highest Co(II) ion content a low degree of crystallinity was detected by XRD analysis.

Interaction of cobalt(II), nickel(II) and zinc(II) with humic-like ligands studied by ESI-MS and ion-exchange method

The interactions of Co(II), Ni(II) and Zn(II) with humic acid and O-donor humic-like ligands were studied by the ion-exchange and electrospray ionization mass spectrometry (ESI-MS) methods. Interactions were confirmed by differences between the values of chromatogram peak areas for monocom- ponent (ligand) and binary systems (ligand with metal ion) by a newly deve- loped ESI-MS 5 µL-loop injection technique. The Schubert ion exchange method was used for the determination of the stability constants of the formed complexes at pH 4.0 and I = 0.01 mol dm -3 . Comparing the values of log K for complexes formed by di-positive metal ions with humic, benzoic and salicylic acids, it could be concluded that the interaction strengths of d-metals followed the Irving-Williams order: Co(II) Zn(II). The obtained values of log K indicated that Pb(II) ions affect the strongest interactions with all the investigated ligands. Complexation of humic acids macromolecules possessing O-donor binding sites as major binding sites could be predicted and modeled following the same order of interaction strength as the Irving-Wil- liams order.