Photoactivatable organometallic pyridyl ruthenium(II) arene complexes

The synthesis and characterization of a family of piano-stool RuII arene complexes of the type [(η6-arene)Ru(N,N′)(L)][PF6]2, where arene is p-cymene (p-cym), hexamethylbenzene (hmb), or indane (ind), N,N′ is 2,2′-bipyrimidine (bpm), 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendio), or 4,7-diphenyl-1,10-phenanthroline (bathophen), and L is pyridine (Py), 4-methylpyridine (4-MePy), 4-methoxypyridine (4-MeOPy), 4,4′-bipyridine (4,4′-bpy), 4-phenylpyridine (4-PhPy), 4-benzylpyridine (4-BzPy), 1,2,4-triazole (trz), 3-acetylpyridine (3-AcPy), nicotinamide (NA), or methyl nicotinate (MN), are reported, including the X-ray crystal structures of [(η6-p-cym)Ru(bpm)(4-MePy)]2+ (2), [(η6-p-cym)Ru(bpm)(4-BzPy)]2+ (6), [(η6-p-cym)Ru(bpm)(trz)]2+ (7), [(η6-p-cym)Ru(phen)(Py)]2+ (10), and [(η6-ind)Ru(bpy)(Py)]2+ (13). These complexes can selectively photodissociate the monodentate ligand (L) when excited with UVA or white light, allowing strict control of the formation of the reactive aqua species [(η6-arene)Ru(N,N′)(OH2)]2+ that otherwise would not form in the dark. The photoproducts were characterized by UV–vis absorption and 1H NMR spectroscopy. DFT and TD-DFT calculations were employed to characterize the excited states and to obtain information on the photochemistry of the complexes. All the RuII pyridine complexes follow a relatively similar photochemical L-ligand dissociation mechanism, likely to occur from a series of 3MC triplet states with dissociative character. The photochemical process proved to be much more efficient when UVA-range irradiation was used. More strikingly, light activation was used to phototrigger binding of these potential anticancer agents with discriminating preference toward 9-ethylguanine (9-EtG) over 9-ethyladenine (9-EtA). Calf thymus (CT)-DNA binding studies showed that the irradiated complexes bind to CT-DNA, whereas the nonirradiated forms bind negligibly. Studies of CT-DNA interactions in cell-free media suggest combined weak monofunctional coordinative and intercalative binding modes. The RuII arene complexes [(η6-p-cym)Ru(bpm)(Py)]2+ (1), [(η6-p-cym)Ru(bpm)(4-MeOPy)]2+ (3), [(η6-p-cym)Ru(4,4′-bpy)]2+ (4), [(η6-hmb)Ru(bpm)(Py)]2+ (8), [(η6-ind)Ru(bpm)(Py)]2+ (9), [(η6-p-cym)Ru(phen)(Py)]2+ (10), [(η6-p-cym)Ru(bathophen)(Py)]2+ (12), [(η6-p-cym)Ru(bpm)(NA)]2+ (15), and [(η6-p-cym)Ru(bpm)(MN)]2+ (16) were cytotoxic toward A2780 human ovarian cancer cell line in the absence of photoirradiation (IC50 values in the range of 9.0–60 μM)

Bipyrimidine ruthenium(II) arene complexes : structure, reactivity and cytotoxicity

The synthesis and characterization of complexes [(η6-arene)Ru(N,N′)X][PF6], where arene is para-cymene (p-cym), biphenyl (bip), ethyl benzoate (etb), hexamethylbenzene (hmb), indane (ind) or 1,2,3,4-tetrahydronaphthalene (thn), N,N′ is 2,2′-bipyrimidine (bpm) and X is Cl, Br or I, are reported, including the X-ray crystal structures of [(η6-p-cym)Ru(bpm)I][PF6], [(η6-bip)Ru(bpm)Cl][PF6], [(η6-bip)Ru(bpm)I][PF6] and [(η6-etb)Ru(bpm)Cl][PF6]. Complexes in which N,N′ is 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione or 4,7-diphenyl-1,10-phenanthroline (bathophen) were studied for comparison. The RuII arene complexes undergo ligand-exchange reactions in aqueous solution at 310 K; their half-lives for hydrolysis range from 14 to 715 min. Density functional theory calculations on [(η6-p-cym)Ru(bpm)Cl][PF6], [(η6-p-cym)Ru(bpm)Br][PF6], [(η6-p-cym)Ru(bpm)I][PF6], [(η6-bip)Ru(bpm)Cl][PF6], [(η6-bip)Ru(bpm)Br][PF6] and [(η6-bip)Ru(bpm)I][PF6] suggest that aquation occurs via an associative pathway and that the reaction is thermodynamically favourable when the leaving ligand is I > Br ≈ Cl. pK a* values for the aqua adducts of the complexes range from 6.9 to 7.32. A binding preference for 9-ethylguanine (9-EtG) compared with 9-ethyladenine (9-EtA) was observed for [(η6-p-cym)Ru(bpm)Cl][PF6], [(η6-hmb)Ru(bpm)Cl]+, [(η6-ind)Ru(bpm)Cl]+, [(η6-thn)Ru(bpm)Cl]+, [(η6-p-cym)Ru(phen)Cl]+ and [(η6-p-cym)Ru(bathophen)Cl]+ in aqueous solution at 310 K. The X-ray crystal structure of the guanine complex [(η6-p-cym)Ru(bpm)(9-EtG-N7)][PF6]2 shows multiple hydrogen bonding. Density functional theory calculations show that the 9-EtG adducts of all complexes are thermodynamically preferred compared with those of 9-EtA. However, the bmp complexes are inactive towards A2780 human ovarian cancer cells. Calf thymus DNA interactions for [(η6-p-cym)Ru(bpm)Cl][PF6] and [(η6-p-cym)Ru(phen)Cl][PF6] consist of weak coordinative, intercalative and monofunctional coordination. Binding to biomolecules such as glutathione may play a role in deactivating the bpm complexes

The role of chemokine genes in the formation of terminal stage of chronic renal failure

The data on the role of chemokine genes (+1931A/T CCL4, A/G CXCL11 (rs4512021), -403A/G CCL5, C/G CCL2 (rs2857657), -801G/A CXCL12) in the formation of terminal stage of chronic renal failure, in patients with chronic glomerulonephritis, is presented in the work. It was established, that the allele A CXCL11 (rs4512021) (OR = 1.65) was the marker for the development of terminal stage of chronic renal insufficiency, and the genotype GG CXCL11was a protective factor for the development of terminal stage of chronic renal failure (OR = 0.22

Recognition of Avirulence Gene AvrLm1 from Hemibiotrophic Ascomycete Leptosphaeria maculans Triggers Salicylic Acid and Ethylene Signaling in Brassica napus

Interaction of a plant with a fungal pathogen is an encounter with hundreds of molecules. In contrast to this, a single molecule often decides between the disease and resistance. In the present article, we describe the defense responses triggered by AvrLm1, an avirulence gene from a hemibiotrophic ascomycete, Leptosphaeria maculans, responsible for an incompatible interaction with Brassica napus. Using multiple hormone quantification and expression analysis of defense-related genes, we investigated signaling events in Rlm1 plants infected with two sister isolates of L. maculans differentiated by the presence or absence of AvrLm1. Infection with the isolate carrying AvrLm1 increased the biosynthesis of salicylic acid (SA) and induced expression of the SA-associated genes ICS1, WRKY70, and PR-1, a feature characteristic of responses to biotrophic pathogens and resistance gene-mediated resistance. In addition to SA-signaling elements, we also observed the induction of ASC2a, HEL, and CHI genes associated with ethylene (ET) signaling. Pharmacological experiments confirmed the positive roles of SA and ET in mediating resistance to L. maculans. The unusual cooperation of SA and ET signaling might be a response to the hemibiotrophic nature of L. maculans. Our results also demonstrate the profound difference between the natural host B. napus and the model plant Arabidopsis in their response to L. maculans infection

The effectiveness of glucocorticoid therapy in patients with chronic glomerulonephritis, depending on the polymorphic markers of cytokine genes

The paper presents the results of a study of interrelationships of polymorphic cytokine loci (rs1800629 TNFα, rs909253 Ltα, rs767455 TNFR1 and rs1800469 TGFβ-1) with the features of glucocorticoid therapy in patients with chronic glomerulonephriti

Genetic factors of decreased kidney function in patients with chronic glomerulonephritis

The article presents the results of studying the interaction of polymorphic variants of vascular homeostasis genes (I/D ACE, 4а/4b eNOS, S311C PON2, (-6) A/G AGT, (-1166) A/С AGTR1, G/A GNB3 (rs.2301339), G460W ADD1, (+46) G/A ADRB2, K198N EDN1, (+6986) G/A CYP3A5) with the state of renal function at the onset of chronic glomerulonephriti

Clinical and genetic research of chronic glomerulonephritis

The paper presents data on interaction of candidate genes (S311C PON2, (-6)A/G AGT, (-1166)A/CAGTR1, (-592)C/A IL-10, VNTR IL-1Ra, T113M IL-9, K198N EDN1, (+46)G/A ADRB2, G/A GNB3 (rs.2301339)) with oligogenic and continuous characters of chronic glomerulonephriti

Risk factors and molecular entities of the etiopathogenesis of the knee osteoarthritis (literature review)

The literature review allowed us to identify the molecular mechanisms of etiopathogenesis of knee osteoarthritis and the major risk factors for the patholog

ПЕРЕБУДОВА ХІМІЧНОГО СКЛАДУ КІСТКОВОЇ ТКАНИНИ У ВІКОВОМУ АСПЕКТІ ЗА РІЗНИХ РЕЖИМІВ РУХОВОЇ АКТИВНОСТІ

A deep study of the adjustment processes of bone, its structure, chemical composition, adaptive capacity is a necessary condition for clarifi cation of the infl uence of labor, sports and a number of trades that occur in connection with the scientifi c and technical progress on the body. Simulation of the diff erent modes of motor activity does not fully meet the training process rights in physical education and sport. However, the results obtained in this pilot study are related to the disclosure of general biological laws based on individual and genetically determined characteristics of individuals, knowledge of which will serve as a morphological substantiation of the training process and prediction of structural changes in the skeleton at various modes of physical activity, injury prevention, and the development of osteoporosis.Глубокое изучение процессов перестройки костной ткани, ее строения, химического состава, адаптационных возможностей является необходимым условием выявления закономерностей влияния труда, спорта и ряда профессий, возникающих в связи с научно-техническим прогрессом на организм. Моделирование различных режимов двигательной активности в полной мере соответствует тренировочным процессам человека в физической культуре и спорте. Однако результаты, полученные при данном экспериментальном исследовании, имеют отношение к раскрытию общебиологических закономерностей, основанных на индивидуальных и генетически обусловленных особенностях индивидуумов, знание которых послужит морфологическим обоснованием тренировочного процесса и прогнозированию структурных преобразований в скелете при различных режимах двигательной активности, предотвращению травм и развития остеопороза.Глибоке вивчення процесів перебудови кісткової тканини, її будови, хімічного складу, адаптаційних можливостей є необхідною умовою виявлення закономірностей впливу праці, спорту та ряду професій, що виникають у зв’язку з науково-технічним прогресом, на організм. Моделювання різних режимів рухової активності не в повній мірі відповідає тренувальним процесам людини у фізичній культурі та спорті. Однак результати, отримані при даному експериментальному дослідженні, мають відношення до розкриття загальнобіологічних закономірностей, що ґрунтуються на індивідуальних і генетично обумовлених особливостях індивідуумів, знання котрих послужить морфологічним обґрунтуванням тренувального процесу і прогнозуванню структурних перетворень в скелеті при різних режимах рухової активності, запобіганню травм та розвитку остеопорозу

Cerebrospinal fluid growth-associated protein 43 in multiple sclerosis

Neurodegeneration in multiple sclerosis (MS) correlates with disease progression and reparative processes may be triggered. Growth-associated protein 43 (GAP-43) exhibits induced expression during axonal growth and reduced expression during MS progression. We aimed to evaluate if GAP-43 can serve as a biomarker of regeneration in relapsing-remitting MS (RRMS) and whether disease-modifying therapies (DMTs) influence GAP-43 concentration in cerebrospinal fluid (CSF). GAP-43 was measured using an enzyme-linked immunosorbent assay in 105 MS patients (73 RRMS, 12 primary progressive MS, 20 secondary progressive MS) and 23 healthy controls (HCs). In 35 of the patients, lumbar puncture, clinical assessment, and magnetic resonance imaging was performed before initiation of therapeutic intervention, and at follow-up. CSF GAP-43 concentration was significantly lower in progressive MS compared with HCs (p = 0.004) and RRMS (p =  < 0.001) and correlated negatively with disability (p = 0.026). However, DMTs did not alter CSF GAP-43. Interestingly, in RRMS CSF GAP-43 levels were higher in patients with signs of active inflammatory disease than in patients in remission (p = 0.042). According to CSF GAP-43 concentrations, regeneration seems reduced in progressive MS, increased during disease activity in RRMS but is unaffected by treatment of highly active DMTs