Correlation between HSAB Principle and Substitution Reactions in Bioinorganic Reactions

Substitution reactions are a type of reactions where one functional group or ligand is substituted by another. They could be electrophilic or nucleophilic, depending upon whether the reagent is involved. Complex compounds could be involved in a number of substitution reactions such as ligand exchange, solvent exchange, complexation or anation reactions, solvolysis, acid and base hydrolysis, inter- and intramolecular isomerization, racemization, and metal ion reaction. Hard-soft acid–base principle (HSAB) contributes to better understanding of the mechanism of nucleophilic substitution reactions of transition metal complexes. Metal–ligand bonds in transition metal compounds are closely related to the HSAB nature of metals and their preferred ligands. Also, the principle is qualitatively useful to predict the preference of the metal for the ligand in bioinorganic reactions

Mechanism of Interactions of Zinc(II) and Copper(II) Complexes with Small Biomolecules

Over the past few decades, transition metal complexes have attracted considerable attention in medicinal inorganic chemistry, especially as synthetic metallonucleases and metal-based anticancer drugs that are able to bind to DNA under physiological conditions. The use of metal-based drugs presents the most important strategy in the development of new anticancer and antimicrobial agents. Negative side effects during treatment (such as vomiting, resistance, nephrotoxicity, ototoxicity, neurotoxicity and cardiotoxicity) prompted researchers to design new classes of DNA and protein targeting metal-based anticancer agents with potential in vitro selectivity and less toxicity. Knowledge of mechanism of the interaction zinc(II) and copper (II) ions with biomolecules and other relevant ligands is essential for understanding the cellular biology of delivery complexes to DNA and proteins. Results obtained from investigations provide useful information for the future design of potential zinc- and copper-based anticancer drugs. Different mechanism of interactions with selected biomolecules compared to platinum-based drugs has been observed

Reaction of a 3-aryilidene-2-thiohydantoin derivative with polymeric trans-[CuCl2(DMSO)(2)](n) complex: unexpected isomerization to dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2)

The 3-arylidene-2-thiohydantoin derivative, 3-[(2-hydroxybenzylidene)amino]-2-thioxoimidazolidin-4-one, was synthesized in a two-step condensation reaction of 2-hydroxybenzaldehyde, thiosemicarbazide and ethyl chloroacetate. The ligand was structurally characterized by NMR and IR spectroscopy, as well as by elemental analysis. In the reaction of the well-known polymeric trans-[CuCl2(DMSO)(2)](n) complex with the polydentate thiohydantoin type ligand, instead of the corresponding copper thiohydantoin complex, unexpectedly, the dinuclear cis-[{CuCl(DMSO)(2)}(mu-Cl)](2) complex (1) was formed predominantly as the final stable product. The structure of the complex 1 was confirmed by single crystal X-ray diffraction analysis. The cis-complex is obtained through assisted isomerization of the trans-form, in which the thiohydantoin derivative has a crucial role

Cytomegalovirus infection may be oncoprotective against neoplasms of B-lymphocyte lineage: single-institution experience and survey of global evidence

Although cytomegalovirus (CMV) is not considered tumorigenic, there is evidence for its oncomodulatory effects and association with hematological neoplasms. Conversely, a number of experimental and clinical studies suggest its putative anti-tumour effect. We investigated the potential connection between chronic CMV infection in patients with B-lymphocyte (B-cell) malignancies in a retrospective single-center study and extracted relevant data on CMV prevalences and the incidences of B-cell cancers the world over

The relationship between internet use and depressive symptoms among high school students

Introduction/Objective. Problematic internet use has been associated with various mental health problems. The objective of this study was to investigate the internet use and its relationship with depressive symptoms among high school students. Methods. This cross-sectional observational study included 620 students from the first to the fourth grade of four high schools in Požarevac, Serbia. The research data were obtained from an ad hoc designed questionnaire on socio-demographic data, health habits, and the internet use, Internet Addiction Test (IAT) and Center for Epidemiological Studies Depression Scale for Children (CES-DC). Results. Out of 620 students (66.9% girls) there were 389 respondents (62.7%) who reported normal (n = 40), or average internet use (n = 349) with a mild level of addiction, while 226 (36.5%) subjects belonged to problematic internet use group, and five students (0.8%) showed a high level of internet addiction. A CES-DC score ≥ 15, considered indicative of clinically significant depressive symptoms, was found significantly more frequent among internet addicts compared to internet normal users (78.4% vs. 46.5%, respectively). Among internet addicts there was a significantly higher percentage of those who used psychologist/psychotherapist help compared to internet normal users (29.4% vs. 12.1%, respectively). The logistic regression analysis showed that internet addiction (IAT score ≥ 50) was the strongest independent predictor of clinically significant depressive symptoms (OR = 3.32; 95% CI = 2.24–4.91), after adjusting for confounders (female gender, urban living, Tik Tok and Twitter use, sports activities, and the use of the internet for learning or for aimless “surfing”). Conclusion. We show that internet addiction is positively related to clinically significant depressive symptoms among high school students. Health education focused on the proper use of the internet may be regarded as mental health promotion

Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agent

The four novel complexes [{cis-PtCl(NH3)2(μ-4,4′ -bipyridyl)ZnCl(terpy)}](ClO4)2 (C1), [{trans-PtCl(NH3)2(μ- 4,4′ -bipyridyl)ZnCl(terpy)}](ClO4)2 (C2), [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C3) and [{trans- PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C4) (where terpy = 2,2′ :6′ ,2′ ′ -terpyridine) were synthesized and characterized. Acid–base titrations and concentration dependent kinetic measurements for the reactions with biologically relevant ligands such as guanosine-5′ -monophosphate (5′ -GMP), inosine-5′ -monophosphate (5′ -IMP) and glutathione (GSH), were studied at pH 7.4 and 37 ◦C. The binding of the heterometallic bridged cis- or trans- Pt(II)-Zn(II) complexes to calf thymus DNA (CT-DNA) was studied by UV absorption and fluorescence emission spectroscopy and molecular docking. The results indicated that the complexes bind strongly to DNA, through groove binding, hydrogen bonds, and hydrophobic or electrostatic interaction. The possible in vitro DNA protective effect of cis- and trans-Pt-L-Zn complexes has shown that C3 had significant dose-dependent DNA-protective effect and the same ability to inhibit peroxyl as well as hydroxyl radicals. Antiproliferative effect of the complexes, mRNA expression of apoptosis and repair-related genes after treatment in cancer cells indicated that newly synthesized C2 exhibited highly selective cytotoxicity toward colon carcinoma HCT116 cells. Only treatment with trans analog C2 induced effect similar to the typical DNA damaging agent such as cisplatin, characterized by p53 mediated cell response, cell cycle arrest and certain induction of apoptotic related genes. Both cis- and trans-isomers C1 and C2 showed potency to elicit expression of PARP1 mRNA and in vitro DNA binding

Modes of Interactions with DNA/HSA Biomolecules and Comparative Cytotoxic Studies of Newly Synthesized Mononuclear Zinc(II) and Heteronuclear Platinum(II)/Zinc(II) Complexes toward Colorectal Cancer Cells

A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl2(terpytBu)] (C1), [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C2), [{trans-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C3), [{cis-PtCl(NH3)2(μ-4,4′-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C4) and [{trans-PtCl(NH3)2(μ-4,4′-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C5) (where terpytBu = 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower Kb and Ksv constant values compared to cisplatin analogs. The lowest Ksv value belonged to complex C1, while C4 exhibited the highest. Molecular docking studies reveal that the binding of complex C1 to DNA is due to van der Waals forces, while that of C2–C5 is due to conventional hydrogen bonds and van der Waals forces. The tested complexes exhibited variable cytotoxicity toward mouse colorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and non-cancerous mouse mesenchymal stem cells (mMSC). Particularly, the mononuclear C1 complex showed pronounced selectivity toward cancer cells over non-cancerous mMSC. The C1 complex notably induced apoptosis in CT26 cells, effectively arrested the cell cycle in the G0/G1 phase, and selectively down-regulated Cyclin D