Using DFT-based computational chemistry calculations (ωB97XD/def2-tzvp//ωB97XD/def2-svp/svpfit + ZPE(ωB97XD/def2-svp/svpfit)), binding energies of noble gases encapsulated in a series of ...dodecahedrane molecules (general formula: X20H20 where X = C, Si, Ge, Sn and Pb, and X20 where X = N, P, As, Sb and Bi) were calculated to learn about the noble gas selectivity. Based on calculated binding energies, the Sn20H20 cage can best accommodate noble gases with a medium size radius (Ar and Kr), while the Pb20H20 dodecahedrane cage is best suited for noble gases with the larger radii (Xe and Rn). On the other hand, from the elements of the V main group of the periodic table, the Bi20 cage has shown the best results to selectively encapsulate Ar and Kr, with the amounts of energy being released being −5.24 kcal/mol and −6.13 kcal/mol, respectively. By monitoring the geometric changes of all here-reported host cages upon encapsulating the noble gas guest, the host has shown minor to no flexibility, testifying to the high rigidity of the dodecahedrane structure which was further reflected in very high encapsulating energies.
Based on computational chemistry calculations (ωB97XD/def2‐tzvp//ωB97XD/def2‐svp/svpfit+ZPE(ωB97XD/def2‐svp/svpfit)), binding energy of tubular3,6,6,6arene to accommodate noble gases and a series of ...29 small gases were calculated. Based on the gained results, Rn (−17.52 kcal/mol) from the series of noble gases is best suited to be accommodated. In the series of noble gases, the binding energy increases linearly with increasing gas radii. From the series of 29 small guests, IF3 and C2I2 (~ −23 kcal/mol) have the best proclivity to be most effectively accommodated in the tubularene, with other 26 exhibiting favorable encapsulation energies on various scales depending on their voluminosity and structure, and only NI3 with the unfavorable complexation energy of 13.87 kcal/mol. Investigated gases, depending on the size, are placed at the different position inside the tube‐like cavity of the tubularene. The structure of the tubularene, independent of the hosted guest species, has remained very rigid, with its atom's rearrangements withing an error margin.
Substituting the O-C
2
H
4
-O-moiety of 2.2.2 by the O
2
CCO
2
-core of oxalic acid leads to the new Lehn-type cryptand M ⊂ 2
Oxa
.2
Oxa
.2
Oxa
m+
. We explored by quantum chemical methods ...(B3LYP/LANL2DZp) the complexation behaviour and compared it with the original cryptand 2.2.2. The cryptands 2
Oxa
.2
Oxa
.2
Oxa
and 2.2.2 exhibit the same ion selectivity against alkaline and alkaline earth metal cation (K
+
followed by Rb
+
; Ba
2+
preferred over Sr
2+
). The exchange of the OC
2
H
4
O-moiety by the O
2
CCO
2
-moiety (the subsequent exchange of sp
3
- by sp
2
-carbon atoms) makes 2
Oxa
.2
Oxa
.2
Oxa
less flexible in the OCCO-diether angle as 2.2.2. This rigidity results in higher complexation energies for M ⊂ 2
Oxa
.2
Oxa
.2
Oxa
m+
and that the twisting of the dihedral angle CN...NC improves the nesting of the guest cations in the cryptand 2
Oxa
.2
Oxa
.2
Oxa
.
The biological activity of six structurally similar tetradentate Schiff base copper(II) complexes, namely Cu(ethylenediamine-bis-acetylacetonate) (CuAA) and five derivatives where two methyl groups ...are replaced by phenyl, (CuPP), CF3 (CuTT) or by mixed groups CH3/CF3 (CuAT), Ph/CF3 (CuPT), and Ph/CH3 (CuAP) has been investigated. The set of antioxidant assays was performed, and the results were expressed as IC50 and EC50 values. The series of complexes showed interesting bioactivity and were investigated for the determination of antioxidant, antifungal, antimicrobial, and cytotoxic activity. A significant antioxidant behavior was exhibited by complex CuAA, greater than Trolox in the Oxygen Radical Absorbance Capacity (ORAC) assay. Antibacterial assay over Gram-positive and Gram-negative pathogenic bacterial strains and some fungal pathogens were studied. Antiproliferative activity of complexes in two human tumor cell lines, breast adenocarcinoma MCF-7, colon adenocarcinoma LS-174, and normal fibroblast cells-MRC-5, examined the effect on cell cycle progression. The significant cytotoxic potential, comparable to cisplatin cytotoxicity, was determined in human breast cancer cell line-MCF-7 with IC50 values being 17.53–31.40 μM and human colon cancer cell line-LS-174 with IC50 values being 15.22–23.92 μM. All tested compounds showed nearly twice more selectivity toward cancer cell lines than normal cells. The interactions of complexes with human serum albumin (HSA), the most prominent protein in plasma, were investigated using spectroscopic fluorescence techniques. The complexes bind to human serum albumin at multiple sites (n = 0.2–1.9), displaying a moderate binding constant Ka = 4.1–12.4 × 104 M−1. The molecular docking experiment effectively showed complex binding to HSA and DNA molecular fragments.
Molecular docking simulations of copper(II) complex Cu(ethylenediamine-bis-acetylacetonate) and five derivatives with DNA were studied to assess their biological activity in addition to in vitro investigations. Display omitted
•The biological activity of six Schiff base Copper(II) complexes has been investigated;•Antioxidant, antimicrobial, and cytotoxicity investigations were performed;•The Schiff base Copper(II) complexes showed good antibacterial and antifungal activity;•Relativel high binding constants show tight binding affinity to protein.
In this paper, we investigated water exchange reactions and substitution of aqua RuII complexes of general formula Ru(terpy)(N^N)(H2O)2+ (where N^N = ethylenediamine (en), 1,2‐(aminomethyl)pyridine ...(ampy) and 2,2′‐bipyridine (bipy)) by ammonia and thioformaldehyde. These reactions were studied in detail by applying conceptual density functional theory. This approach enabled us to gain further insight into the underlying reaction mechanism at the microscopic level (involving only direct participants of the reaction, without the influence of the solvent) and to put the concept of reaction mechanism on a quantitative basis. The course of the chemical reaction along the reaction coordinate ξ, is rationalized in terms of reaction energy, force, dipole moment, and reaction electronic flux (REF). The results yield and characterize the significant influence of an intermolecular hydrogen bond formed between the entering and the spectator ligand to the overall energy barrier of the reactions.
Conceptual DFT calculations can be a powerful tool in providing a better understanding of the reaction mechanism at the microscopic level, without the interference of the solvent molecules. Throughout this paper these kind of calculations were used to investigate water substitution reactions on RuII‐aqua complexes. The results yield and characterize the significant influence of an intermolecular hydrogen bond formed between the entering and the spectator ligand to the overall energy barrier of the reactions.
Four new complexes Pd(H2LtBu)ClCl (Pd1), Pt(H2LtBu)ClCl (Pt1), Pd(Me2LtBu)ClCl (Pd2) and Pt(Me2LtBu)ClCl (Pt2) (where H2LtBu = 2,6-bis(5-(tert-butyl)-1H-pyrazol-3-yl)pyridine and ...Me2LtBu = 2,6-bis(5-(tert-butyl)-1-methyl-1H-pyrazol-3-yl)pyridine) were synthesized and characterized by elemental microanalysis, IR, 1H NMR and ESI-MS methods. The reactivity of complexes towards thiourea (Tu), l-methionine (l-Met), l-cysteine (l-Cys) and guanosine-5′-monophosphate (5′-GMP) was investigated. The obtained order was established as follows: Tu > l-Cys > l-Met > 5′-GMP. Complexes Pd1 and Pt1, that contain H2LtBu as chelator, showed higher reactivity towards biomolecules than those with Me2LtBu. The interaction of complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) was studied by UV–Vis and fluorescence spectroscopy. The results have shown that complexes can bind to DNA exhibiting high binding constants (Kb = 104 M−1). Obtained results during the examination of competitive reaction with ethidium bromide (EB) showed that complexes can replace EB-bound DNA. High values of binding constants indicate good binding affinity of complexes towards BSA. We evaluated the stability differences between complexes based on terpy as well as H2LtBu/Me2LtBu by DFT calculations (B3LYP(CPCM)/LANL2DZp), showing that both tridentate ligand systems lead to complexes of similar stability. The results of biological testing showed that all complexes exert moderate to high selective cytotoxicity, inducing apoptosis and autophagy in HeLa and PANC-1 tumor cell lines. Pd1 exhibited the strongest cytotoxic effect. Finally, cell cycle analysis showed that in HeLa cells Pd1, Pd2 and Pt1 induced accumulation of cells in S phase, whereas in PANC-1 cells Pd2 and Pt1 induced G2/M cycle arrest and Pd1 induced G0/G1 arrest.
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•Synthesis and characterization of four new platinum(II) and palladium(II) complexes.•Substitution reactions with biological relevant nucleophiles were examined.•Interactions with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were studied.•Stability difference of complexes with terpy and H2LtBu/Me2LtBu ligands are calculated.•Cytotoxic activity and impact on cell cycle were established on different cell lines.
The synthesis, characterization, solution and redox stability, kinetic, mechanistic, DNA/BSA/HSA binding, DFT and molecular docking studies were performed of five new mononuclear gold(III) complexes.
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Five new gold(III) complexes, with general formula Au(NN)Cl2+ for complexes 1–3 and Au(NN)23+ for complexes 4–5 (where NN is 3-((2-((5-phenyl-1H-pyrazol-3-yl)methoxy)naphthalene-3-yloxy)methyl)-5-phenyl-1H-pyrazole – L1, (3-((2-((5-phenyl-1H-pyrazol-3-yl)methoxy) phenoxy)methyl)-5-phenyl-1H-pyrazole – L2, (3-((2-((5-naphthalen-2-yl)-1H-pyrazol-3-yl)methoxy)phenoxy)methyl)-5-(naphthalen-3-yl)-1H-pyrazole – L3), were synthesized and characterized by elemental analysis, 1H NMR, IR, UV–Vis, ESI-MS and conductometry. Also, ligand L2 was characterized by X-ray analysis. Stability of complexes in water and in Hepes buffer was confirmed by UV–Vis. Kinetics and mechanism of the substitution reactions of 1–3 with guanosine-5′-monophosphate (5′-GMP), glutathione (GSH) and.
l-Methionine (l-Met) were studied by stopped-flow technique. Obtained results have shown that complex 1 is the most reactive, while the reactivity of the nucleophiles decreases in order: GSH > 5′-GMP > l-Met. Calculated values of the entropy of activation support an associative mechanism. Redox stability of complexes 1–3 was investigated in the presence of the same biomolecules by cyclic voltametry. Obtained voltammograms showed reduction of gold(III) up to gold(0). DNA binding studies in the presence of ethidium bromide (EB) and 2-(4-hydroxyphenyl)-5-5-(4-methylpipera-zine-1yl)-benzimidazo-2-yl-benzimidazole (HOE) were performed by UV–Vis, fluorescence spectroscopy and viscosity measurements, in order to assess the binding mode. The results showed that gold(III) complexes interact with calf-thymus (CT-DNA) via covalently binding mode rather than via intercalation. Also, all complexes shown high values of binding constants for the interactions with bovine serum albumin (BSA) and human serum albumin (HSA). Furthermore, the binding studies with CT-DNA and BSA/HSA were supported by molecular docking. The strong connection between structure and reactivity of gold(III) complexes toward biologically important molecules was confirmed.
•Synthesis and biological properties of Schiff bases.•IC50 values in DPPH radical and superoxide anion radical scavenging activities were 15.64 µg/mL and 54.72 μg/mL, respectively (even better than ...positive control ascorbic acid).•B1 and B2 showed great antibacterial activity (MIC values ranged from 0.15 to 1.25 mg/mL).•C4 and B1 compounds showed very strong antifungal activity (MIC values ranged from 0.07 to 1.25 mg/mL).
In order to make an advancement in the discovery of the more effective ways to eliminate ROS, which causes oxidative stress or to eliminate the harmful microorganisms from the organism in humans, and bearing in mind the fact that Schiff bases belong to a class of biologically active compounds, a series of Schiff bases were synthesized and tested to evaluate their antioxidant and antimicrobial activity. DPPH, superoxide anion, and reducing power assays were used in assessing the antioxidative potential of studied compounds. Among tested compounds, the B1 compound showed the largest activity in all antioxidant assays. IC50 values in DPPH radical and superoxide anion radical scavenging activities were 15.64 µg/mL and 54.72 μg/mL, respectively (even better than positive control ascorbic acid). Moreover, these compounds had effective reducing power (absorbance was in the range 2.415–1.270, depending on the concentrations tested). A high antioxidant effect was also found in B2 and C3 compounds. The remaining tested compounds showed slightly weaker antioxidant activity. Besides, the antioxidative capacity of selected compounds was studied by density functional theory (DFT). The antimicrobial activity of B1, B2 and C1–4 compounds was examined towards eight microorganisms (four species of bacteria and five species of fungi) using the microdilution method. Among tested compounds, B1 and B2 showed marked antibacterial activity (MIC values ranged from 0.15 to 1.25 mg/mL), while C4 and B1 compounds showed very strong antifungal activity (MIC values ranged from 0.07 to 1.25 mg/mL). Molecular docking simulations were performed to better understand the binding modes selected compounds with DNA and BSA, as well as to comprehend their antioxidative or antimicrobial activity.
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With the application of DFT calculations (ωB97XD/def2-SVP/SVPfit), the ability and mechanism of noble gas encapsulation by cryptophane was investigated. Based on the applied model reaction, by ...monitoring geometric changes and investigating the non-covalent interactions between the studied hosts and the noble gases, the size of the host did not necessarily play a decisive role in the selective encapsulation of the guests. Rather the adjustment of the host's interior and functionalization of its "gates" can be significant in tuning the affinity of cryptophanes.
•The new histamine Schiff bases and coresponding spinaceamines were synthesized.•Antimicrobial activity of newly synthetized Schiff bases was evaluated.•Binding of Schiff bases to the DNA and BSA was ...investigated.•The docking study has shown binding affinity of new histamine Schiff bases to BSA and DNA.
The synthesis of eight new histamine-based Schiff bases and cyclic derivatives spinaceamines was accomplished by the reaction of corresponding aldehydes and histamine as amine-counterpart in absolute ethanol. Bearing in mind that the presence of the imino group/or spinaceamine core in the organic molecular scaffold could bring prominent pharmaceutical properties, all synthesised compounds have been screened for their antimicrobial activities against a range of different bacterial and fungal strains and antioxidant activity, as well as for interactions with bovine serum albumin (BSA) and DNA molecules. According to the observed MIC values, the best activity for both, fungal and bacterial species, was displayed by the compound 3c bearing histamine and quinoline moieties in the structure, especially for Staphylococcus aureus. Results obtained in the fluorescence quenching experiments have confirmed ability of tested compounds for DNA and BSA binding, while docking simulations revealed the site I of sub-domain IIA of BSA as a location of binding sites of tested compounds, as well as the minor grove and intercalation interactions with quite similar possibilities to be considered as compounds DNA-binding modes. Further, the molecular docking studies also gave insight into binding modes to the targeted enzymes (CYP51, cytochrome P450 and TyRS) related to the antifungal and antibacterial potential of tested compounds. Two compounds were selected, Schiff base 3c and spinaceamine 4d, to assess the stability of compounds under the physiological conditions (UV-vis spectroscopic study) and in silico ADME properties (SwissADME software), where both compounds have shown the stability after 72 hours in selected medium, and a potential as a drug based on their ADME properties.
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