Effects of surface cooling and of roughness on the heating (including transition) to the windward plane-of-symmetry of the shuttle orbiter

The theoretical heat-transfer distributions are compared with experimental heat-transfer distributions obtained in Tunnel B at AEDC using a 0.0175 scale model of the space shuttle orbiter configuration for which the first 80% of the windward surface was roughened by a simulated tile misalignment. The theoretical solutions indicate that thinning the boundary layer by surface cooling increased the nondimensionalized value of the local heat-transfer coefficient. Tile misalignment did not significantly affect the heat-transfer rate in regions where the boundary layer was either laminar or turbulent

Synthesis and Characterization of New Ethylenediamine Platinum(IV) Complexes Containing Lipophilic Carboxylate Ligands

A series of new ethylenediamine (en) platinum(IV) complexes of the type Pt(IV)enX2A2, with X2  = cyclobutane-1,1-dicarboxylato (CBDCA), dichloro or bis(decanoato) and A = acetato, dodecanoato, tetradecanoato, hexadecanoato, octadecanoato, adamantanecarboxylato (Ad) or 3α, 12α-diformoxy-5β-cholato (DFCA) were synthesized and characterized by elemental analysis, infrared and NMR (1H  and  13C) spectroscopic techniques. Previous platinum(IV) compounds were usually restricted to trans-dihydroxo or trans-dichloro platinum(IV) complexes. Recently trans-dicarboxylato platinum(IV) complexes with mainly acetate, trifluoracetate or short-chain carboxylate groups (<11 carbons) in the axial position have been described in the literature[1,2,3]. In this paper we report on the synthesis and characterization of a new class of ethylenediamine platinum(IV) compounds that have high lipophilic long-chain carboxylate ligands either in the axial or equatorial position. The platinum(IV) compounds with the lipophilic trans-carboxylate ligands in the axial position were prepared by acylation of the trans-dihydroxo platinum(IV) species using an acyl halide in the presence of pyridine. In contrast to previous publications[1] the yields were excellent (up to 94%!)

Synthesis of (N,N'-Bis(2-Hydroxyethyl)Ethane-1,2-Diamine)Malonatoplatinum(II) and X-Ray Crystal Structure of the Cis-R,S-Isomer

Hydroxyethyl substituted amineplatinum(II) and (IV) complexes are an interesting class of platinum based antitumour compounds due to their uncoordinated hydroxy groups. These hydroxy groups could play an important role in the mode of action of such complexes with respect to their ability to act as donor or acceptor for hydrogen bonds. Moreover, their chemistry in solution is of interest because it was found that there is the possibility of an intramolecular attack to form ethanolatoamine chelated species which are responsible for very stable monoadducts with 5'-GMP. Furthermore, there is the possibility of derivatisation at the OH site to form a new series of platinum compounds which may be used for a carrier mediated transport to tumour tissues. In this context a series of (N,N'-bis(2-hydroxyethyl)ethane-l,2-diamine)-platinum(II) complexes has been synthesised. During purification of one of the platinum based compounds, it was possible to isolate (SP-4-3)-R,S-(N,N'-bis(2-hydroxyethyl)ethane-l,2-diamine)malonatoplatinum(ll) and to resolve the structure by single crystal structure analysis. Intra- and intermolecular hydrogen bonds have been found which may explain the spontaneous crystallisation of the cis-R,S isomer and the stabilisation of the boat conformation of the malonatoplatinum(II) six-membered ring

Synthesis and in vitro Antitumor Potency of (Cyclohexane-1,2-Diamine)Platinum(II) Complexes with Aminotris(Methylenephosphonic Acid) as Bone-Seeking Ligand

In order to develop platinum complexes with selective activity in primary and secondary bone malignancies and with the aim to optimize antitumor activity, platinum(II) complexes with aminotris(methylenephosphonic acid) as bone-seeking (osteotropic) ligand have been synthesized, characterized and tested in the cisplatin-sensitive ovarian carcinoma cell line CH1. As non-leaving diamine ligands, which are decisive for the cellular processing of DNA adducts, cis-R,S-cyclohexane-1,2-diamine, trans-S,S-cyclohexane-1,2-diamine and trans-R,R-cyclohexane-1,2-diamine have been used, resulting in complexes 1, 2, and 3, respectively. The cytotoxicity of the complexes under investigation decreases in the order 3 > 2 > 1 which is in accord with structure-activity relationships with other (cyclohexane-1,2- diamine)platinum(II) and platinum(IV) complexes: Both trans complexes (2 and 3) display a higher in vitro potency than the corresponding cis isomer (I), with the trans-R,R isomer (3) being the most active in this series. In comparison to the analogous (cyclohexane-1,2-diamine)platinum(II) complexes with bis(phosphonomethyl)aminoacetic acid as osteotropic carrier ligand, the cytotoxicity of 1-3 was found to be 1.5 – 2 fold higher, which is explainable by a different coordination mode of the phosphonic acid ligands (acetato versus phosphonato)

A new monoclinic polymorph of dichlorido­tetra­kis(dimethyl sulfoxide)­ruthenium(II)

The title compound, cis,fac-dichloridotetra­kis(dimethyl sulfoxide)-κ3 S,κO-ruthenium(II), [RuCl2(C2H6OS)4], was obtained from newly synthesized ruthenium complexes of 3-amino-2-chloro­pyridine. The Ru atom has a distorted octa­hedral coordination with two cis-oriented chloride ligands and four dimethyl sulfoxide ligands. Three of the sulfoxide ligands are S-bonded in a fac configuration, while the fourth is O-bonded. The title compound represents a new, and fourth, polymorph of the complex. Two other monoclinic forms and an ortho­rhom­bic modification have been reported previously

The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes

A wide variety of steric and electronic features can be incorporated into transition metal coordination complexes, offering the prospect of rationally-designed therapeutic agents with novel mechanisms of action. Here we compare the chemical reactivity and anticancer activity of organometallic OsII complexes [Os(η6-arene)(XY)Z]PF6 where arene = p-cymene or biphenyl, XY = N,N′-chelated phenyliminopyridine or phenylazopyridine derivatives, and Z = Cl or I. The X-ray crystal structure of [Os(η6-p-cym)(Impy-OH)I]PF6·0.5CH2Cl2·H2O (Impy-OH = 4-[(2-pyridinylmethylene)amino]-phenol) is reported. Like the azopyridine complexes we reported recently (Dalton Trans., 2011, 40, 10553–10562), some iminopyridine complexes are also potently active towards cancer cells (nanomolar IC50 values). However we show that, unlike the azopyridine complexes, the iminopyridine complexes can undergo aquation, bind to the nucleobase guanine, and oxidize coenzyme nicotine adenine dinucleotide (NADH). We report the first detection of an Os-hydride adduct in aqueous solution by 1H NMR (−4.2 ppm). Active iminopyridine complexes induced a dramatic increase in the levels of reactive oxygen species (ROS) in A549 lung cancer cells. The anticancer activity may therefore involve interference in the redox signalling pathways in cancer cells by a novel mechanism

Platinum(IV)-Loaded Degraded Glycol Chitosan as Efficient Platinum(IV) Drug Delivery Platform

A new class of anticancer prodrugs was designed by combining the cytotoxicity of platinum(IV) complexes and the drug carrier properties of glycol chitosan polymers: Unsymmetrically carboxylated platinum(IV) analogues of cisplatin, carboplatin and oxaliplatin, namely (OC-6-44)-acetatodiammine(3-carboxypropanoato)dichloridoplatinum(IV), (OC-6-44)-acetaodiammine(3-carboxypropanoato)(cyclobutane-1,1-dicarboxylato)platinum(IV) and (OC-6-44)-acetato(3-carboxypropanoato)(1R,2R-cyclohexane-1,2-diamine)oxalatoplatinum(IV) were synthesised and conjugated via amide bonding to degraded glycol chitosan (dGC) polymers with different chain lengths (5, 10, 18 kDa). The 15 conjugates were investigated with 1H and 195Pt NMR spectroscopy, and average amounts of platinum(IV) units per dGC polymer molecule with ICP-MS, revealing a range of 1.3–22.8 platinum(IV) units per dGC molecule. Cytotoxicity was tested with MTT assays in the cancer cell lines A549, CH1/PA-1, SW480 (human) and 4T1 (murine). IC50 values in the low micromolar to nanomolar range were obtained, and higher antiproliferative activity (up to 72 times) was detected with dGC-platinum(IV) conjugates in comparison to platinum(IV) counterparts. The highest cytotoxicity (IC50 of 0.036 ± 0.005 µM) was determined in CH1/PA-1 ovarian teratocarcinoma cells with a cisplatin(IV)–dGC conjugate, which is hence 33 times more potent than the corresponding platinum(IV) complex and twice more potent than cisplatin. Biodistribution studies of an oxaliplatin(IV)–dGC conjugate in non-tumour-bearing Balb/C mice showed an increased accumulation in the lung compared to the unloaded oxaliplatin(IV) analogue, arguing for further activity studies

Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(II) and palladium(II).

The synthesis, spectroscopic and X-ray structural characterization of copper(II) and palladium(II) complexes with aziridine ligands as 2-dimethylaziridine HNCH2CMe2 (a), the bidentate N-(2-aminoethyl)aziridines C2H4NC2H4NH2 (b) or CH2CMe2NCH2CMe2NH2 (c) as well as the unsaturated azirine NCH2CPh (d) are reported. Cleavage of the cyclometallated Pd(II) dimer [μ-Cl(C6H4CHMeNMe2-C,N)Pd]2 with ligand a yielded compound [Cl(NHCH2CMe2)(C6H4CHMe2NMe2-C,N)Pd] (1a). The reaction of the aziridine complex trans-[Cl2Pd(HNC2H4)2] with an excess of aziridine in the presence of AgOTf gave the ionic chelate complex trans-[(C2H4NC2H4NH2-N,N′)2Pd](OTf)2 (2b) which contains the new ligand b formed by an unexpected insertion and ring opening reaction of two aziridines (“aziridine dimerization”). CuCl2 reacted in pure HNC2H4 or HNCH2CMe2 (b) again by “dimerization” to give the tris-chelated ionic complex [Cu(C2H4NC2H4NH2-N,N′)3]Cl2 (3b) or the bis-chelated complex [CuCl(C2H2Me2NC2H2Me2NH2-N,N′)2]Cl (4c). By addition of 2H-3-phenylazirine (d) to PdCl2, trans-[Cl2Pd(NCH2CPh)2] (5d) was formed. All new compounds were characterized by NMR, IR and mass spectra and also by X-ray structure analyses (except 3b). Additionally the cytotoxic effects of these complexes were examined on HL-60 and NALM-6 human leukemia cells and melanoma WM-115 cells. The antimicrobial activity was also determined. The growth of Gram-positive bacterial strains (S. aureus, S. epidermidis, E. faecalis) was inhibited by almost all tested complexes at the concentrations of 37.5–300.0 μg mL−1. However, MIC values of complexes obtained for Gram-negative E. coli and P. aeruginosa, as well as for C. albicans yeast, mostly exceeded 300 μg mL−1. The highest antibacterial activity was achieved by complexes 1a and 2b. Complex 2b also inhibited the growth of Gram-negative bacteria. Graphical abstract: Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(ii) and palladium(ii

Quaternary Ammonium Palmitoyl Glycol Chitosan (GCPQ) Loaded with Platinum-Based Anticancer Agents—A Novel Polymer Formulation for Anticancer Therapy

Quaternary ammonium palmitoyl glycol chitosan (GCPQ) has already shown beneficial drug delivery properties and has been studied as a carrier for anticancer agents. Consequently, we synthesised cytotoxic platinum(IV) conjugates of cisplatin, carboplatin and oxaliplatin by coupling via amide bonds to five GCPQ polymers differing in their degree of palmitoylation and quaternisation. The conjugates were characterised by 1H and 195Pt NMR spectroscopy as well as inductively coupled plasma mass spectrometry (ICP-MS), the latter to determine the amount of platinum(IV) units per GCPQ polymer. Cytotoxicity was evaluated by the MTT assay in three human cancer cell lines (A549, non-small-cell lung carcinoma; CH1/PA-1, ovarian teratocarcinoma; SW480, colon adenocarcinoma). All conjugates displayed a high increase in their cytotoxic activity by factors of up to 286 times compared to their corresponding platinum(IV) complexes and mostly outperformed the respective platinum(II) counterparts by factors of up to 20 times, also taking into account the respective loading of platinum(IV) units per GCPQ polymer. Finally, a biodistribution experiment was performed with an oxaliplatin-based GCPQ conjugate in non-tumour-bearing BALB/c mice revealing an increased accumulation in lung tissue. These findings open promising opportunities for further tumouricidal activity studies especially focusing on lung tissue