Multiple coordination modes of hemilabile 3-dimethylaminopropyl chalcogenolates in platinum(II) complexes: Synthesis, spectroscopy and structures

The reactions of N,N-dimethylaminopropyl chalcogenolates with platinum(II) compounds have been carried out and complexes of the types [PtCl(ECH₂CH₂CH₂NMe₂)]₂ (1) (E = S (1a) and Se (1b)), [Pt(ECH₂CH₂CH₂NMe₂)₂]_n (2) (E = S (2a) and Se (2b)), [(PtCl₂)₂{(Me₂NCH₂CH₂CH₂E)₂}]_n (3), [PtX(SeCH₂CH₂CH₂NMe₂)]₂ (4) (X = SePh (4a) and OAc (4b)) and [PtCl(ECH₂CH₂CH₂NMe₂)(PR₃)]_n (5) (E = S, Se, Te) have been isolated. These complexes have been characterized by elemental analysis, IR, UV-Vis, NMR (¹H, ¹³C, ³¹P, ⁷⁷Se, ¹⁹⁵Pt) spectroscopy and FAB mass spectral data. The structures of [PtCl(SeCH₂CH₂CH₂NMe₂)]₂ (1b) and [PtCl(SCH₂CH₂CH₂NMe₂)(PPr₃)]₂ (5a) have been established by single crystal X-ray diffraction data. Both the molecules have dimeric structures. In 1b, two platinum atoms are held together by symmetrically bridging Se atoms of the chelating selenolate groups. In 5a, two thiolates form a four-membered Pt₂S₂ bridge with dangling NMe₂ groups.     

An antiferromagnetically coupled trinuclear Cu(II) complex containing μ(O,O′), μ(O) carboxylates and μ(O) phenoxide bridges

The trinuclear complex [L₂Cu₃(CF₃CO₂)₄] (1) has been synthesized and its crystal structure determined. It consists of a linear arrangement of Cu(II) centers. The central copper atom is bonded to six oxygen atoms and has a tetragonally distorted octahedral geometry, while the terminal copper atoms are bonded to three oxygen and two nitrogen atoms and show a distorted square pyramidal geometry. The complex shows di-μ(O,O′) syn-syn carboxylate bridging as well as monoatomic (μ-O) bridging, along with phenolate (μ-O) oxygen bridging. Cryomagnetic investigations in the range 2-300 K revealed an antiferromagnetic spin exchange interaction with J = −95.7 cm⁻¹, based on the isotropic exchange model H_ex = −2J[S₁ · S₂ + S₂ · S₃].     

Apoptotic Mode of Cell Death in Substantia Nigra Following Intranigral Infusion of the Parkinsonian Neurotoxin,MPP<Superscript>+</Superscript> in Sprague-Dawley Rats: Cellular,Molecular and Ultrastructural Evidences

The potent parkinsonian neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is known to cause dopaminergic neurodegeneration in nigrostriatal system. In the present study we investigated the nuclear morphology of cells in the substantia nigra pars compacta (SNpc) region of rats following unilateral intranigral infusion of the active metabolite, 1-methyl-4-phenyl pyridinium ion (MPP⁺), which resulted in a dose-dependent and prolonged dopamine depletion in the ipsilateral striatum. There appeared a substantial loss of tyrosine hydroxylase immunoreactive neurons in the SNpc that received the neurotoxin. Specific nuclear staining with Hoechst 33342 or acridine orange revealed bright pyknotic, shrunken, distorted nuclei and condensed chromatin with perinuclear nucleolus respectively following visualization with the former and latter dyes in the ipsilateral SNpc, as compared to the round, intact nuclei and centrally positioned nucleolus in the contralateral side. Ultrastructural details of the nucleus under transmission electron microscope confirmed distorted nuclear organization with shrunken or condensed nuclei and disrupted nuclear membrane. These features are typical of nucleus undergoing apoptosis, and suggest that MPP⁺ causes dopaminergic neuronal death through an apoptotic mode. Typical laddering pattern of genomic DNA isolated from the ipsilateral SN in agarose gel electrophoresis conclusively established apoptosis following intranigral administration of MPP⁺ in rats. Rebecca Banerjee and Sen Sreetama contributed equally to this paper.     

Prognostic significance of the histomorphometric features of bone marrow trephine biopsies in patients with chronic myeloid leukemia

OBJECTIVE: To study the correlation of histomorphometric data of bone marrow trephine biopsies at the time of initial diagnosis in chronic myeloid leukemia (CML) patients with the patient prognosis. STUDY DESIGN: A total of 40 CML patients were divided equally in group I (developed accelerated phase or blast crisis within 18 months of initial diagnosis of chronic phase of CML) and group II (developed accelerated phase or blast crisis > 30 months after initial diagnosis of chronic phase of CML). The clinical, hematologic and histomorphometric data were compared in the 2 groups of CML patients. RESULTS: The percentage of bone marrow promyelocytes was significantly increased in group I. On morphometry, the number of blasts per square millimeter, the area of reticulin fibers per square millimeter and the percentage area occupied by reticulin fibers were statistically significant. CONCLUSION: There seems to be grounds for hope for predicting prognosis of CML patients at initial diagnosis based on histomorphometric findings. The percentage area of reticulin fibers and the number of blasts per square millimeter are important prognostic predictors in histomorphometry data.     

An efficient method for producing an indexed, insertional-mutant library in rice

Generation of an indexed, saturated, insertional-mutant library is an aid to understanding the functions of genes in an organism. However, 10 years of work by many investigators have not yet yielded such a library in rice. The major reason is that determining the chromosomal locations of a very large number of random insertion mutants by flanking sequence analysis is highly labor intensive, and therefore, libraries that do exist have not been indexed. We report here an efficient procedure to construct an indexed, region-specific, insertional-mutant library of rice. The procedure makes use of efficient long-PCR-based high-throughput indexing, coupled with a random but anchored population of Ds transposants. Long-PCR indexing allows rapid and simultaneous determination of the chromosomal locations of a large number of mutants that surround a particular anchor line, thus converting a random library into an indexed one. Such a library can be used directly, without the need to screen a large random library for a desired mutant plant.     

Structure and Evolution of the Archaeal Lipid Synthesis Enzyme sn-Glycerol-1-phosphate Dehydrogenase

One of the most critical events in the origins of cellular life was the development of lipid membranes. Archaea use isoprenoid chains linked via ether bonds to sn-glycerol 1-phosphate (G1P), whereas bacteria and eukaryotes use fatty acids attached via ester bonds to enantiomeric sn-glycerol 3-phosphate. NAD(P)H-dependent G1P dehydrogenase (G1PDH) forms G1P and has been proposed to have played a crucial role in the speciation of the Archaea. We present here, to our knowledge, the first structures of archaeal G1PDH from the hyperthermophilic methanogen Methanocaldococcus jannaschii with bound substrate dihydroxyacetone phosphate, product G1P, NADPH, and Zn²⁺ cofactor. We also biochemically characterized the enzyme with respect to pH optimum, cation specificity, and kinetic parameters for dihydroxyacetone phosphate and NAD(P)H. The structures provide key evidence for the reaction mechanism in the stereospecific addition for the NAD(P)H-based pro-R hydrogen transfer and the coordination of the Zn²⁺ cofactor during catalysis. Structure-based phylogenetic analyses also provide insight into the origins of G1PDH.     

In Vivo Studies in Rhodospirillum rubrum Indicate That Ribulose-1,5-bisphosphate Carboxylase/Oxygenase (Rubisco) Catalyzes Two Obligatorily Required and Physiologically Significant Reactions for Distinct Carbon and Sulfur Metabolic Pathways

All organisms possess fundamental metabolic pathways to ensure that needed carbon and sulfur compounds are provided to the cell in the proper chemical form and oxidation state. For most organisms capable of using CO₂ as sole source of carbon, ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) catalyzes primary carbon dioxide assimilation. In addition, sulfur salvage pathways are necessary to ensure that key sulfur-containing compounds are both available and, where necessary, detoxified in the cell. Using knock-out mutations and metabolomics in the bacterium Rhodospirillum rubrum, we show here that Rubisco concurrently catalyzes key and essential reactions for seemingly unrelated but physiologically essential central carbon and sulfur salvage metabolic pathways of the cell. In this study, complementation and mutagenesis studies indicated that representatives of all known extant functional Rubisco forms found in nature are capable of simultaneously catalyzing reactions required for both CO₂-dependent growth as well as growth using 5-methylthioadenosine as sole sulfur source under anaerobic photosynthetic conditions. Moreover, specific inactivation of the CO₂ fixation reaction did not affect the ability of Rubisco to support anaerobic 5-methylthioadenosine metabolism, suggesting that the active site of Rubisco has evolved to ensure that this enzyme maintains both key functions. Thus, despite the coevolution of both functions, the active site of this protein may be differentially modified to affect only one of its key functions.