Validated Capillary Zone Electrophoresis Method for Impurity Profiling and Determination of NiII(3-OMe-Salophene)

A capillary zone electrophoresis method was developed for the determination of NiII(3-OMe-salophene), a substance with anticancer activity in vitro. A fused silica capillary (56 cm × 100 µm) was used for this purpose. The method was optimized in terms of parameters affecting the electrophoretic conditions in order to optimize separation efficiency and total time of migration. The analysis was best performed using an operating buffer of 50 mM borate, adjusted to pH 9.3, mixed with acetonitrile (50%, v/v) as organic modifier. Injections were performed hydrodynamically by applying a pressure of 50 mbar for 8 s, and a 30 kV separation voltage was selected at 25 °C. Detection was carried out at 250 nm using diode array detector (DAD). The method allowed the separation of NiII(3-OMe-salophene) from four other structurally related impurities in a total migration time (tm) of 8 min. Peak identification was achieved using the standard reference of individual impurities. The purity of the migrated NiII(3-OMe-salophene) was confirmed by Ultra-violet (UV) scan overlay depending on DAD. The linear ranges for the determination of NiII(3-OMe-salophene) was 400–20,000 ng mL−1 with limit of detection (LOD) of 120 ng mL−1. Acceptable intra-day and inter-day precisions were achieved (%relative standard deviation (RSD) results were less than 0.76% and 0.30%, respectively). The proposed method was assessed for greenness and compared to reported methodologies to prove superiority

Rhenium mixed-ligand complexes with S,N,S-tridentate thiosemicarbazone/thiosemicarbazide ligands

Rhenium(V) complexes containing tridentate thiosemicarbazones/thiosemicarbazides (H2L1) derived from N-[N′,N′-dialkylamino(thiocarbonyl)]benzimidoyl chlorides with 4,4-dialkylthiosemicarbazides have been synthesized by ligand-exchange reactions starting from [ReOCl(L1)]. The chlorido ligand of [ReOCl(L1)] (4) is readily replaced and reactions with ammonium thiocyanate or potassium cyanide give [ReO(NCS)(L1)] (6) and [ReO(CN)(L1)] (7), respectively. The reaction of (NBu4)[ReOCl4] with H2L1 and two equivalents of ammonium thiocyanate, however, gives in a one-pot reaction [ReO(NCS)2(HL1)] (8), in which the pro-ligand H2L1 is only singly deprotonated. An oxo-bridged, dimeric nitridorhenium(V) compound of the composition [{ReN(HL1)}2O] (11) is obtained from a reaction of (NBu4)[ReOCl4], H2L1 and sodium azide. The six-coordinate complexes [ReO(L1)(Ph2btu)] (12), where HPh2btu is N,N-diphenyl-N′-benzoylthiourea, can be obtained by treatment of [ReOCl(L1)] with HPh2btu in the presence of NEt3. Studies of the antiproliferative effects of the [ReOX(L1)] system (X = Cl−, NCS− or CN−) on breast cancer cells show that the lability of a monodentate ligand seems to play a key role in the cytotoxic activity of the metal complexes, while the substitution of this ligand by the chelating ligand Ph2btu− completely terminates the cytotoxicity

Dichloro-[1-(hydroxyphenyl)-2-phenylethylenediamine]platinum(II) complexes: testing on the human ovarian cancer cell lines NIH: OVCAR3 and SK OV 3

The diastereoisomeric dichloro-[1-(2-, 3- and 4-hydroxyphenyl)-2-phenylethylenediamine]platinum(II) complexes were tested on two human ovarian cancer cell lines NIH: OVCAR-3 and SK-OV-3, both resistant against cisplatin. Dichloro-[threo-1-(3-hydroxyphenyl)-2-phenylethylenediamine]platinum(II) (threo-5-PtCl2) proved to be the most active representative of the new series, producing cytocidal effects at a concentration range of 2.5 to 5.0 microM on the NIH: OVCAR-3 cell line. On the more resistant SK-OV-3 cell line, threo-5-PtCl2 was only moderately active, while in combination with BSO, a GSH level lowering compound, threo-5-PtCl2 showed a strong synergistic effect

[DL-1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II), a new compound for the therapy of ovarian cancer

The synthesis of diastereoisomeric [1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes, DL-3-PtCl2 and meso-3-PtCl2, and their evaluation on the hormone-independent, human MDA-MB231 breast cancer cell line, on the cisplatin-sensitive and -resistant L1210 leukemia cell line, on the cisplatin-resistant human NIH:OVCAR 3 ovarian cancer cell line, on the P-388 leukemia of the mouse and on the cisplatin-sensitive and -resistant Ehrlich ascites tumor of the mouse are described. On all tumor models DL-3-PtCl2 produces a marked inhibitory effect. The diastereoisomer meso-3-PtCl2 is less active and more toxic. It is striking that DL-3-PtCl2 leads to a pronounced inhibition of all cisplatin-resistant tumors. At non-toxic concentrations DL-3-PtCl2 produces cytocidal effects on the NIH:OV-CAR 3 cell line. Therefore DL-3-PtCl2 is of interest for further evaluation for the therapy of ovarian cancer

Fundamental Limits on Wavelength, Efficiency and Yield of the Charge Separation Triad

In an attempt to optimize a high yield, high efficiency artificial photosynthetic protein we have discovered unique energy and spatial architecture limits which apply to all light-activated photosynthetic systems. We have generated an analytical solution for the time behavior of the core three cofactor charge separation element in photosynthesis, the photosynthetic cofactor triad, and explored the functional consequences of its makeup including its architecture, the reduction potentials of its components, and the absorption energy of the light absorbing primary-donor cofactor. Our primary findings are two: First, that a high efficiency, high yield triad will have an absorption frequency more than twice the reorganization energy of the first electron transfer, and second, that the relative distance of the acceptor and the donor from the primary-donor plays an important role in determining the yields, with the highest efficiency, highest yield architecture having the light absorbing cofactor closest to the acceptor. Surprisingly, despite the increased complexity found in natural solar energy conversion proteins, we find that the construction of this central triad in natural systems matches these predictions. Our analysis thus not only suggests explanations for some aspects of the makeup of natural photosynthetic systems, it also provides specific design criteria necessary to create high efficiency, high yield artificial protein-based triads

A 'snip' in time: what is the best age to circumcise?

<p>Abstract</p> <p>Background</p> <p>Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also pediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves.</p> <p>Discussion</p> <p>We show here that infancy is an optimal time for clinical circumcision because an infant's low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used.</p> <p>Summary</p> <p>Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision.</p

Tumor inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes, III: Evaluation of the mammary tumor inhibiting properties

Diastereomeric diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) sulfates and nitrates produce a strong inhibition of the hormone-dependent MXT-M 3.2 mammary carcinoma of the B6D2F1 mouse. Besides an interference in the DNA synthesis in analogy to cisplatin a lowering of the estrogen level due to an interference in steroid biosynthesis is suggested as the mode of action. In contrast to the R,R/S,S configurated diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) salts the corresponding R,S configurated compounds are also markedly active on the hormone-independent MXT-Ovex mammary carcinoma of the B6D2F1 mouse

Synthesis and evaluation of the anti-mammary tumor activity and of the estrogenic side effects of [1,2-bis(2,6-dihalo-3-hydroxyphenyl)ethylenediamine]platinum(II) complexes

The synthesis and structural characterization of mammary tumor-inhibiting, diastereomeric [1,2-bis(2,6-dihalo-3-hydroxyphenyl)ethylenediamine]platinum(II) complexes with 2,6-Cl2, 2-F, 6-Cl, 2-Cl, 6-F and 2,6-F2 substituents (1-PtSO4 to 4-PtSO4) are described. L are synthesized by stereoselective meso-meso and D,L-D,L diaza-Cope-rearrangement reactions and coordinated to Pt(II) with K2PtI4 to give PtLI2. The subsequent reaction with Ag2SO4 leads to PtLSO4. They were tested for their antitumor activities of the hormone-sensitive and-insensitive MXT mammary carcinoma implanted in mice (MXT-MC, ER+ and MXT-MC, ER-). Complexes with F atoms in the neighborhood of the 3-hydroxy group showed strong inhibitory effects on the MXT-MC, ER+. The best effects were found for the diastereomeric 2,6-F2-substituent-complexes. These complexes are strongly active both on the MXT-MC, ER+ and the MXT-MC, ER- and cause no estrogenic side effects

Investigation of the Conformational influences on the estrogenic activity of 1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamines and of their platinum(II) complexes, II. Synthesis and studies on the estrogenic activity of cis- and trans[bis(2,6-dichloro-4-hydroxybenzylamine)]dihaloplatinum(II) complexes

2,6-Dichloro-4-hydroxybenzylamine (1) and its N-Me (2) and N-Et (3) derivs. were synthesized and tested for estrogen receptor affinity as well as for estrogenic activity. In contrast to their related highly active 1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamines (meso-4 - meso-6) none of the benzylamines showed hormonal activity. The coordination of the benzylamine 1 to platinum did not lead to an estrogenic compd. The reasons for the different activity of [meso-1,2(bis-2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (meso-4-PtCl2) and cis[bis(2,6-dichloro-4-hydroxybenzylamine)]dichloroplatinum(II) (cis-1-PtCl2), the latter of which can be considered as a ring-opened counterpart of the highly active meso-4-PtCl2, are thoroughly discussed under inclusion of conformational facts. The results of this and the preceding work show, that the pharmacophore meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine (meso-4) which is exclusively responsible for the estrogenic activity of meso-4-PtCl2 causes comparable hormonal effects in two different conformations with O-O distances of .apprx.8 .ANG. (complex) and of .apprx.12 .ANG. (diamine). Therefore, two binding sites for estrogens in their receptor are discussed

Breast cancer-inhibiting properties of leaving group derivatives of [1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine]platinum(II)

Meso-PtLX2 (I; L = 1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine; X = 0.5SO4, NO3, PhSO3, cyclobutane-1,1-dicarboxylate (CBDC), isocitrate) and the 2 diastereomeric PtLCl2 were prepd. The influence of the leaving groups of I on several murine tumors: P388 leukemia, MTX-M3.2 breast cancer (hormone-sensitive) and MXT-Ovex breast cancer (hormone-insensitive) was studied. The compds. with leaving groups, which are more easily exchangeable by H2O mols. (SO42-, NO3-, PhSO3-, produced stronger tumor inhibition and also more pronounced side effects than those with moderately stable (Cl-) or stable (CBDC, isocitrate) bond leaving groups. Against the P388 leukemia, none of the tested complexes were cytotoxic to the same extent as cis-Pt(NH3)2Cl2 (II). The MXT-Ovex breast cancer, however, was strongly inhibited by meso-PtLSO4 which was even more active than II. The hormone-sensitive MXT-M3.2 breast cancer underwent 78% inhibition by the most interesting compd. of I leaving-group series (i.e. meso-PtLCl2) at the nontoxic dosage of 5 micro mol/kg. With the well-tolerated, more active diastereomer, D,L-PtLCl2, 99% inhibition of tumor growth could be achieved at a dose of 10 micro mol/kg