Helsingin lämpösaareke ajallisena ja paikallisena ilmiönä

The urban heat island phenomenon is the most well-known all-year-round urban climate phenomenon. It occurs in summer during the daytime due to the short-wave radiation from the sun and in wintertime, through anthropogenic heat production. In summertime, the properties of the fabric of city buildings determine how much energy is stored, conducted and transmitted through the material. During night-time, when there is no incoming short-wave radiation, all fabrics of the city release the energy in form of heat back to the urban atmosphere. In wintertime anthropogenic heating of buildings and traffic deliver energy into the urban atmosphere. The initial focus of Helsinki urban heat island was on the description of the intensity of the urban heat island (Fogelberg 1973, Alestalo 1975). In this project our goal was to carry out as many measurements as possible over a large area of Helsinki to give a long term estimate of the Helsinki urban heat island. Helsinki is a city with 550 000 inhabitants and located on the north shore of Finnish Bay of the Baltic Sea. Initially, comparison studies against long-term weather station records showed that our regular, but weekly, sampling of observations adequately describe the Helsinki urban heat island. The project covered an entire seasonal cycle over the 12 months from July 2009 to June 2010. The measurements were conducted using a moving platform following microclimatological traditions. Tuesday was selected as the measuring day because it was the only weekday during the one year time span without any public holidays. Once a week, two set of measurements, in total 104, were conducted in the heterogeneous temperature conditions of Helsinki city centre. In the more homogeneous suburban areas, one set of measurements was taken every second week, to give a total of 52.The first set of measurements took place before noon, and the second 12 hours, just prior to midnight. Helsinki Kaisaniemi weather station was chosen as the reference station. This weather station is located in a large park in the city centre of Helsinki. Along the measurement route, 336 fixed points were established, and the monthly air temperature differences to Kaisaniemi were calculated to produce monthly and annual maps. The monthly air temperature differences were interpolated 21.1 km by 18.1 km horizontal grid with 100 metre resolution residual kriging method. The following independent variables for the kriging interpolation method were used: topographical height, portion of sea area, portion of trees, fraction of built-up and not built-up area, volumes of buildings, and population density. The annual mean air temperature difference gives the best representation of the Helsinki urban heat island effect- Due to natural variability of weather conditions during the measurement campaign care must be taken when interpretation the results for the monthly values. The main results of this urban heat island research project are: a) The city centre of Helsinki is warmer than its surroundings, both on a monthly main basis, and for the annual mean, however, there are only a few grid points, 46 out of 38 191, which display a temperature difference of more than 1K. b) If the monthly spatial variation is air temperature differences is small, then usually the temperature difference between the city and the surroundings is also small. c) Isolated large buildings and suburban centres create their own individual heat island. d) The topographical influence on air temperature can generally be neglected for the monthly mean, but can be strong under certain weather conditions.

Cobalt(II) complexes of terpyridine bases as photochemotherapeutic agents showing cellular uptake and photocytotoxicity in visible light

Cobalt(II) complexes of terpyridine bases Co(L)(2)](ClO4)(2) (1-3), where L is 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy in 1), 4'-(9-anthracenyl)-2,2':6',2''-terpyridine (an-tpy in 2) and 4'-(1-pyrenyl)-2,2':6',2''-terpyridine (py-tpy in 3), are prepared and their photo-induced DNA and protein cleavage activity and photocytotoxic property in HeLa cells studied. The 1 : 2 electrolytic and three-electron paramagnetic complexes show a visible band near 550 nm in DMF-Tris-HCl buffer. The complexes 1-3 show emission spectral bands at 355, 421 and 454 nm, respectively, when excited at 287, 368 and 335 nm. The quantum yield values for 1-3 in DMF-H2O (2 : 1 v/v) are 0.025, 0.060 and 0.28, respectively. The complexes are redox active in DMF-0.1 M TBAP. The Co(III)-Co(II) and Co(II)-Co(I) couples appear as quasi-reversible cyclic voltammetric responses near 0.2 and -0.7 V vs. SCE, respectively. Complexes 2 and 3 are avid binders to calf thymus DNA giving K-b value of similar to 10(6) M-1. The complexes show chemical nuclease activity. Complexes 2 and 3 exhibit oxidative cleavage of pUC19 DNA in UV-A and visible light. The DNA photocleavage reaction of 3 at 365 nm shows formation of singlet oxygen and hydroxyl radical species, while only hydroxyl radical formation is evidenced in visible light. Complexes 2 and 3 show non-specific photo-induced bovine serum albumin protein cleavage activity at 365 nm. The an-tpy and py-tpy complexes exhibit significant photocytotoxicity in HeLa cervical cancer cells on exposure to visible light giving IC50 values of 24.2 and 7.6 mu M, respectively. Live cell imaging study shows accumulation of the complexes in the cytosol of HeLa cancer cells.

Boxicity and Poset Dimension

Let G be a simple, undirected, finite graph with vertex set V(G) and edge set E(C). A k-dimensional box is a Cartesian product of closed intervals a(1), b(1)] x a(2), b(2)] x ... x a(k), b(k)]. The boxicity of G, box(G) is the minimum integer k such that G can be represented as the intersection graph of k-dimensional boxes, i.e. each vertex is mapped to a k-dimensional box and two vertices are adjacent in G if and only if their corresponding boxes intersect. Let P = (S, P) be a poset where S is the ground set and P is a reflexive, anti-symmetric and transitive binary relation on S. The dimension of P, dim(P) is the minimum integer l such that P can be expressed as the intersection of t total orders. Let G(P) be the underlying comparability graph of P. It is a well-known fact that posets with the same underlying comparability graph have the same dimension. The first result of this paper links the dimension of a poset to the boxicity of its underlying comparability graph. In particular, we show that for any poset P, box(G(P))/(chi(G(P)) - 1) <= dim(P) <= 2box(G(P)), where chi(G(P)) is the chromatic number of G(P) and chi(G(P)) not equal 1. The second result of the paper relates the boxicity of a graph G with a natural partial order associated with its extended double cover, denoted as G(c). Let P-c be the natural height-2 poset associated with G(c) by making A the set of minimal elements and B the set of maximal elements. We show that box(G)/2 <= dim(P-c) <= 2box(G) + 4. These results have some immediate and significant consequences. The upper bound dim(P) <= 2box(G(P)) allows us to derive hitherto unknown upper bounds for poset dimension. In the other direction, using the already known bounds for partial order dimension we get the following: (I) The boxicity of any graph with maximum degree Delta is O(Delta log(2) Delta) which is an improvement over the best known upper bound of Delta(2) + 2. (2) There exist graphs with boxicity Omega(Delta log Delta). This disproves a conjecture that the boxicity of a graph is O(Delta). (3) There exists no polynomial-time algorithm to approximate the boxicity of a bipartite graph on n vertices with a factor of O(n(0.5-epsilon)) for any epsilon > 0, unless NP=ZPP.

DNA Photocleavage and Cytotoxic Properties of Ferrocene Conjugates

Ferrocenyl conjugates 2-ferrocenylimidazophenanthroline (1) and 2-ferrocenylimidazophenanthrene (2) were prepared, characterized, and their photoinduced DNA cleavage and photocytotoxic activity were studied. 2-Phenylimidazophenanthroline (3) was used as a control species. Compound 2 was characterized by X-ray crystallography. The interaction of the compounds with double-stranded calf thymus DNA (CT DNA) was studied. The compounds show good binding affinity to CT DNA with K-b values of approximately 10(5) M-1. Thermal denaturation data suggest the groove binding nature of the compounds. The redox-active compounds show poor chemical nuclease activity in the presence of hydrogen peroxide and glutathione (GSH). Compound 1 exhibits significant DNA photocleavage activity in visible light of 476 and 532 nm. Compound 3 shows only moderate DNA cleavage activity. The positive effect of the ferrocenyl moiety is demonstrated by the DNA photocleavage data. Mechanistic investigations reveal the formation of superoxide as well as hydroxyl radicals as the active species. The photocytotoxicity of the compounds in HeLa cells was studied upon irradiation with visible light (400-700 nm). Compound 1 shows efficient photocytotoxic activity with an IC50 value of 13 mu M, while compounds 2 and 3 are less active with IC50 values of > 50 and 22 mu M, respectively.

Terpyridine Oxovanadium(IV) Complexes of Phenanthroline Bases for Cellular Imaging and Photocytotoxicity in HeLa Cells

Oxovanadium(IV) complexes VO(N-N-N)(N-N)](NO3)(2) (1-4) of (4'-phenyl)-2,2': 6',2 `'-terpyridine (ph-tpy in 1 and 2) or (4'-pyrenyl)-2,2':6',2 `'-terpyridine (py-tpy in 3 and 4) having N-N as 1,10-phenanthroline (phen in 1 and 3) or dipyrido3,2-a:2',3'-c]phenazine (dppz in 2 and 4) are prepared and characterized. The crystal structure of 1 has VO2+ group in VN5O coordination geometry. The terpyridine ligand coordinates in a meridional binding mode. The phen ligand displays a chelating mode of binding with an N-donor site trans to the vanadyl oxo group. The complexes show a d-d band in the range of 710-770 nm in aqueous DMF (4:1 v/v). The complexes exhibit an irreversible V-IV/V-III redox response near -1.0 V vs. SCE in aqueous DMF/0.1 M KCl. The complexes bind to CT DNA giving K-b values within 3.5 x 10(5) to 1.2 x 10(6) M-1. The complexes show poor chemical nuclease activity in dark. Complexes 2-4 show photonuclease activity in UV-A light of 365 nm forming O-1(2) and (OH)-O-center dot. Complex 4 shows DNA photocleavage activity at near-IR light of 785 nm forming (OH)-O-center dot radicals. Complexes 2 and 4 show significant photocytotoxicity in HeLa cancer cells. Uptake of the complexes in HeLa cells, studied by fluorescence imaging, show predominantly cytosolic localization inside the cells.

Photocytotoxicity and DNA photocleavage activity of La(III) and Gd(III) complexes of phenanthroline bases

Lanthanide(II) complexes La(B)(acac)(3)] (1-3) and Gd(B)(acac)(3)] (4-6), where B is a N,N-donor phenanthroline base, viz., 1,10-phenanthroline (phen in 1, 4), dipyrido3,2-d:2',3'-f]quinoxaline (dpq in 2, 5) and dipyrido3,2-a:2',3'-c]phenazine (dppz in 3, 6), have been prepared and characterized. The Gd(111) complexes 4 6 are structurally characterized by single crystal X-ray crystallography. The complexes display GdO6N2 coordination with the ligands showing bidentate chelating mode of bonding. The complexes are non-electrolytic in aqueous DMF and exhibit ligand-centered absorption bands in the UV region. The dppz complexes show a band at 380 nm in DMF. The La(111) complexes are diamagnetic. The Gd(III) complexes are paramagnetic with magnetic moment that corresponds to seven unpaired electrons. The Complexes are avid binders to calf thymus DNA giving K-b values in the range of 4.7 x 10(4) 6.1 x 10(5) M-1 with a relative binding order: 3, 6 (dppz) > 2, 5 (dpq) > 1, 4 (phen). The binding data suggest DNA surface and/or groove binding nature of the complexes. The dpq and dppz complexes efficiently cleave SC DNA to its nicked circular form in UV-A light of 365 nm via formation of both singlet oxygen (O-1(2)) and hydroxyl radical (HO center dot) species. The dppz complexes 3 and 6 exhibit significant PDT effect in He La cervical cancer cells giving respective IC50 value of 460(+/- 50) and 530(+/- 30) nM in UV-A light of 365 rim, and are essentially non-toxic in dark with an IC50 value of >100 mu M. The dppz ligand alone is cytotoxic in dark and UV-A light. A significant decrease in the dark toxicity of the dppz base is observed on binding to the Ln(III) ion while retaining its photocytotoxicity.

Work fluctuations in an elastic dumbbell model of polymers in planar elongational flow

We use a path-integral approach to calculate the distribution P(w, t) of the fluctuations in the work W at time t of a polymer molecule (modeled as an elastic dumbbell in a viscous solvent) that is acted on by an elongational flow field having a flow rate (gamma) over dot. We find that P(w, t) is non-Gaussian and that, at long times, the ratio P(w, t)/ P (-w, t) is equal to expw/(k(B)T)], independent of (gamma) over dot. On the basis of this finding, we suggest that polymers in elongational flows satisfy a fluctuation theorem.

Schiff base oxovanadium(IV) complexes of phenanthroline bases showing DNA photocleavage activity at near-IR light and photocytotoxicity

Oxovanadium(IV) complexes VO(L)(B)](ClO4) (1-3) of N-2-pyridylmethylidine-2-hydroxyphenylamine (HL) Schiff base and phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyrido3,2-d: 2',3'-f] quinoxaline (dpq in 2) or dipyrido3,2-a: 2',3'-c] phenazine (dppz in 3), were prepared, characterized and their DNA binding property, photo-induced DNA cleavage activity and photocytotoxicity in HeLa cells studied. The crystal structure of 1 shows the presence of a VO2+ moiety in VO2N4 coordination geometry. The complexes show a d-d band at similar to 830 nm in DMF. The complexes display an oxidative V(V)-V(IV) response near 0.5 V versus SCE and a reductive V(IV)/V(III) response near -0.65 V in DMF -0.1 M TBAP. The complexes that are avid binders to CT DNA giving K-b values within 7.1 x 10(4) to 3.2 x 10(5) M-1, do not show any significant chemical nuclease activity in presence of 3-mercaptopropionic acid or glutathione. The dpq and dppz complexes are photocleavers of pUC19 DNA in UV-A light of 365 nm forming both O-1(2) and (OH)-O-center dot radicals and in near-IR light of 785 nm forming (OH)-O-center dot radicals. The dppz complex exhibits photocytotoxicity in visible light in HeLa cells (IC50 = 6.8 mu M). Flow-cytometric study on this complex shows a high sub-G1 phase in light compared to dark indicating PDT effect. (C) 2011 Elsevier B. V. All rights reserved.

Remarkable photocytotoxicity in hypoxic HeLa cells by a dipyridophenazine copper(II) Schiff base thiolate

Copper(II) complexes Cu(satp)(L)] (1-3) of a Schiff base thiolate (salicylidene-2-aminothiophenol, H(2)satP) and phenanthroline bases (L), viz. 1,10-phenanthroline (phen in 1), dipyrido3,2-d:2',3'-f]quinoxaline (dpq in 2) and dipyrido3,2-a:2',3'-c]phenazine (dppz in 3), were prepared, characterized and their anaerobic DNA photocleavage activity and hypoxic photocytotoxicity studied. The redox active complexes show the Cu(II)-Cu(I) couple near -0.5 V for 1 and near 0.0 V vs. SCE (saturated calomel electrode) for 2 and 3. The one-electron paramagnetic complexes (similar to 1.85 mu(B)) are avid DNA binders giving K(b) values within 1.0 x 10(5) - 8.0 x 10(5) M(-1). Thermal melting and viscosity data along with molecular docking calculations suggest DNA groove and/or partial intercalative binding of the complexes. The complexes show anaerobic DNA cleavage activity in red light under argon via type-I pathway, while DNA photocleavage in air proceeds via hydroxyl radical pathway. The DFT (density functional theory) calculations reveal a thyil radical pathway for the anaerobic DNA photocleavage activity and suggest the possibility of generation of a transient copper(I) species due to bond breakage between the copper and sulfur to generate the thyil radical. An oxidation of the copper(I) species is likely by oxygen in an aerobic medium or by the buffer medium in an anaerobic condition. Complex 3 exhibits significant photocytotoxicity in HeLa cells (IC(50) = 8.3(+/- 1.0) mu M) in visible light, while showing lower dark toxicity (IC(50) = 17.2(+/- 1.0) mu M). A significant reduction in the dark toxicity is observed under hypoxic cellular conditions (IC(50) = 30.0(+/- 1.0) mu M in dark), while retaining its photocytotoxicity (IC(50) = 8.0(+/- 1.0) mu M). (C) 2011 Elsevier Inc. All rights reserved.

Synthesis and DNA binding studies of Ni(II), Co(II), Cu(II) and Zn(II) metal complexes of N(1),N(5)-bis[pyridine-2-methylene]-thiocarbohydrazone Schiff-base ligand

The thiocarbohydrazone Schiff-base ligand with a nitrogen and sulphur donor was synthesized through condensation of pyridine-2-carbaldehyde and thiocarbohydrazide. Schiff-base ligands have the ability to conjugate with metal salts. A series of metal complexes with a general formula [MCl(2)(H(2)L)]center dot nH(2)O (M=Ni, Co, Cu and Zn) were synthesized by forming complexes of the N(1),N5-bis[pyridine-2-methylene]thiocarbohydrazone (H2L) Schiff-base ligand. These metal complexes and ligand were characterized by using ultraviolet-visible (UV-Vis), Fourier Transform Infrared (FT-IR), (1)H and (13)C NMR spectroscopy and mass spectroscopy, physicochemical characterization, CHNS and conductivity. The biological activity of the synthesized ligand was investigated by using Escherichia coli DNA as target. The DNA interaction of the synthesized ligand and complexes on E. coli plasmid DNA was investigated in the aqueous medium by UV-Vis spectroscopy and the binding constant (K(b)) was calculated. The DNA binding studies showed that the metal complexes had an improved interaction due to trans-geometrical isomers of the complexes than ligand isomers in cis-positions. (C) 2011 Elsevier B.V. All rights reserved.

The generalized Onsager model for the secondary flow in a high-speed rotating cylinder

The generalizations of the Onsager model for the radial boundary layer and the Carrier-Maslen model for the end-cap axial boundary layer in a high-speed rotating cylinder are formulated for studying the secondary gas flow due to wall heating and due to insertion of mass, momentum and energy into the cylinder. The generalizations have wider applicability than the original Onsager and Carrier-Maslen models, because they are not restricted to the limit A >> 1, though they are restricted to the limit R e >> 1 and a high-aspect-ratio cylinder whose length/diameter ratio is large. Here, the stratification parameter A = root m Omega(2)R(2)/2k(B)T). This parameter A is the ratio of the peripheral speed, Omega R, to the most probable molecular speed, root 2k(B)T/m, the Reynolds number Re = rho w Omega R(2)/mu, where m is the molecular mass, Omega and R are the rotational speed and radius of the cylinder, k(B) is the Boltzmann constant, T is the gas temperature, rho(w) is the gas density at wall, and mu is the gas viscosity. In the case of wall forcing, analytical solutions are obtained for the sixth-order generalized Onsager equations for the master potential, and for the fourth-order generalized Carrier-Maslen equation for the velocity potential. For the case of mass/momentum/energy insertion into the flow, the separation-of-variables procedure is used, and the appropriate homogeneous boundary conditions are specified so that the linear operators in the axial and radial directions are self-adjoint. The discrete eigenvalues and eigenfunctions of the linear operators (sixth-order and second-order in the radial and axial directions for the Onsager equation, and fourth-order and second-order in the axial and radial directions for the Carrier-Maslen equation) are determined. These solutions are compared with direct simulation Monte Carlo (DSMC) simulations. The comparison reveals that the boundary conditions in the simulations and analysis have to be matched with care. The commonly used `diffuse reflection' boundary conditions at solid walls in DSMC simulations result in a non-zero slip velocity as well as a `temperature slip' (gas temperature at the wall is different from wall temperature). These have to be incorporated in the analysis in order to make quantitative predictions. In the case of mass/momentum/energy sources within the flow, it is necessary to ensure that the homogeneous boundary conditions are accurately satisfied in the simulations. When these precautions are taken, there is excellent agreement between analysis and simulations, to within 10 %, even when the stratification parameter is as low as 0.707, the Reynolds number is as low as 100 and the aspect ratio (length/diameter) of the cylinder is as low as 2, and the secondary flow velocity is as high as 0.2 times the maximum base flow velocity. The predictions of the generalized models are also significantly better than those of the original Onsager and Carrier-Maslen models, which are restricted to thin boundary layers in the limit of high stratification parameter.

Photo-induced DNA cleavage activity and remarkable photocytotoxicity of lanthanide(III) complexes of a polypyridyl ligand

Lanthanide(III) complexes [Ln(pyphen)(acac)(2)(NO3)] (1, 2), [Ln(pydppz)(acac)(2)(NO3)] (3, 4) and [La(pydppz)(anacac)(2)(NO3)] (5), where Ln is La(III) (in 1, 3, 5) and Gd(III) (in 2, 4), pyphen is 6-(2-pyridyl)-1,10-phenanthroline, pydppz is 6-(2-pyridyl)-dipyrido[3,2-a:2',3'-c] phenazine, anacac is anthracenylacetylacetonate and acac is acetylacetonate, were prepared, characterized and their DNA photocleavage activity and photocytotoxicity studied. The crystal structure of complex 2 displays a GdO6N3 coordination. The pydppz complexes 3-5 show an electronic spectral band at similar to 390 nm in DMF. The La(III) complexes are diamagnetic, while the Gd(III) complexes are paramagnetic with seven unpaired electrons. The molar conductivity data suggest 1 : 1 electrolytic nature of the complexes in aqueous DMF. They are avid binders to calf thymus DNA giving K-b in the range of 5.4 10(4)-1.2 x 10(6) M-1. Complexes 3-5 efficiently cleave supercoiled DNA to its nicked circular form in UV-A light of 365 nm via formation of singlet oxygen (O-1(2)) and hydroxyl radical (HO center dot) species. Complexes 3-5 also exhibit significant photocytotoxic effect in HeLa cancer cells giving respective IC50 value of 0.16(+/- 0.01), 0.15(+/- 0.01) and 0.26 +/-(0.02) mu M in UV-A light of 365 nm, while they are less toxic in dark with an IC50 value of >3 mu M. The presence of an additional pyridyl group makes the pydppz complexes more photocytotoxic than their dppz analogues. FACS analysis of the HeLa cells treated with complex 4 shows apoptosis as the major pathway of cell death. Nuclear localization of complex 5 having an anthracenyl moiety as a fluorophore is evidenced from the confocal microscopic studies.

Boxicity and Poset Dimension

Let G be a simple, undirected, finite graph with vertex set V (G) and edge set E(G). A k-dimensional box is a Cartesian product of closed intervals [a(1), b(1)] x [a(2), b(2)] x ... x [a(k), b(k)]. The boxicity of G, box(G), is the minimum integer k such that G can be represented as the intersection graph of k-dimensional boxes; i.e., each vertex is mapped to a k-dimensional box and two vertices are adjacent in G if and only if their corresponding boxes intersect. Let P = (S, P) be a poset, where S is the ground set and P is a reflexive, antisymmetric and transitive binary relation on S. The dimension of P, dim(P), is the minimum integer t such that P can be expressed as the intersection of t total orders. Let G(P) be the underlying comparability graph of P; i.e., S is the vertex set and two vertices are adjacent if and only if they are comparable in P. It is a well-known fact that posets with the same underlying comparability graph have the same dimension. The first result of this paper links the dimension of a poset to the boxicity of its underlying comparability graph. In particular, we show that for any poset P, box(G(P))/(chi(G(P)) - 1) <= dim(P) <= 2box(G(P)), where chi(G(P)) is the chromatic number of G(P) and chi(G(P)) not equal 1. It immediately follows that if P is a height-2 poset, then box(G(P)) <= dim(P) <= 2box(G(P)) since the underlying comparability graph of a height-2 poset is a bipartite graph. The second result of the paper relates the boxicity of a graph G with a natural partial order associated with the extended double cover of G, denoted as G(c): Note that G(c) is a bipartite graph with partite sets A and B which are copies of V (G) such that, corresponding to every u is an element of V (G), there are two vertices u(A) is an element of A and u(B) is an element of B and {u(A), v(B)} is an edge in G(c) if and only if either u = v or u is adjacent to v in G. Let P(c) be the natural height-2 poset associated with G(c) by making A the set of minimal elements and B the set of maximal elements. We show that box(G)/2 <= dim(P(c)) <= 2box(G) + 4. These results have some immediate and significant consequences. The upper bound dim(P) <= 2box(G(P)) allows us to derive hitherto unknown upper bounds for poset dimension such as dim(P) = 2 tree width (G(P)) + 4, since boxicity of any graph is known to be at most its tree width + 2. In the other direction, using the already known bounds for partial order dimension we get the following: (1) The boxicity of any graph with maximum degree Delta is O(Delta log(2) Delta), which is an improvement over the best-known upper bound of Delta(2) + 2. (2) There exist graphs with boxicity Omega(Delta log Delta). This disproves a conjecture that the boxicity of a graph is O(Delta). (3) There exists no polynomial-time algorithm to approximate the boxicity of a bipartite graph on n vertices with a factor of O(n(0.5-is an element of)) for any is an element of > 0 unless NP = ZPP.

Ferrocene-Conjugated Oxidovanadium(IV) Complexes as Potent Near-IR Light Photocytotoxic Agents

Ferrocene-conjugated oxidovanadium(IV) complexes [VO(Fc-tpy)(B)](ClO4)(2) (1-4) and [VO(Ph-tpy)(dppz)](ClO4)(2) (5) as a control [Fc = (eta(5)-C5H4)Fe-II(eta(5)-C5H5), Fc-tpy = 4'-ferrocenyl-2,2':6',2 `'-terpyridine, Ph-tpy = 4'-phenyl-2,2':6',2 `'-terpyridine, B = heterocyclic base: 2,2'-bipyridine (bpy in 1), 1,10-phenanthroline (phen in 2), dipyridoquinoxaline (dpq in 3), dipyridophenazine (dppz in 4)] were prepared and their DNA binding, DNA photocleavage activity and photocytotoxicity studied. The crystal structure of [VO(Fc-tpy)(bpy)](PF6)(2)center dot 3Me(2)CO shows a vanadyl group in six-coordinate (VON5)-O-IV coordination geometry, in which Fc-tpy and bpy display tridentate meridional and bidentate N-donor axial-equatorial binding modes, respectively. The one-electron paramagnetic complexes exhibit a charge-transfer band near 590 nm in DMF. The V-IV/V-III redox couple in 1-4 appears near -0.7 V, whereas the Fc moiety shows a response near 0.6 V vs. SCE in DMF/0.1 M TBAP. The complexes are good binders to calf thymus DNA with K-b values of 10(4)-10(6) M-1. DNA melting and viscometric data suggest groove and/or partial intercalative DNA binding of the complexes. Complexes 3-5 display DNA photocleavage activity in nearIR light of 785 nm. Complex 4 shows significant photocytotoxicity in visible light (400-700 nm) in HeLa cells with low dark toxicity.

Hydration dynamics of protein molecules in aqueous solution: Unity among diversity

Dielectric dispersion and NMRD experiments have revealed that a significant fraction of water molecules in the hydration shell of various proteins do not exhibit any slowing down of dynamics. This is usually attributed to the presence of the hydrophobic residues (HBR) on the surface, although HBRs alone cannot account for the large amplitude of the fast component. Solvation dynamics experiments and also computer simulation studies, on the other hand, repeatedly observed the presence of a non-negligible slow component. Here we show, by considering three well-known proteins (lysozyme, myoglobin and adelynate kinase), that the fast component arises partly from the response of those water molecules that are hydrogen bonded with the backbone oxygen (BBO) atoms. These are structurally and energetically less stable than those with the side chain oxygen (SCO) atoms. In addition, the electrostatic interaction energy distribution (EIED) of individual water molecules (hydrogen bonded to SCO) with side chain oxygen atoms shows a surprising two peak character with the lower energy peak almost coincident with the energy distribution of water hydrogen bonded to backbone oxygen atoms (BBO). This two peak contribution appears to be quite general as we find it for lysozyme, myoglobin and adenylate kinase (ADK). The sharp peak of EIED at small energy (at less than 2 k(B)T) for the BBO atoms, together with the first peak of EIED of SCO and the HBRs on the protein surface, explain why a large fraction (similar to 80%) of water in the protein hydration layer remains almost as mobile as bulk water Significant slowness arises only from the hydrogen bonds that populate the second peak of EIED at larger energy (at about 4 k(B)T). Thus, if we consider hydrogen bond interaction alone, only 15-20% of water molecules in the protein hydration layer can exhibit slow dynamics, resulting in an average relaxation time of about 5-10 ps. The latter estimate assumes a time constant of 20-100 ps for the slow component. Interestingly, relaxation of water molecules hydrogen bonded to back bone oxygen exhibit an initial component faster than the bulk, suggesting that hydrogen bonding of these water molecules remains frustrated. This explanation of the heterogeneous and non-exponential dynamics of water in the hydration layer is quantitatively consistent with all the available experimental results, and provides unification among diverse features.