And then came Complex Project Management

The subject of management is renowned for its addiction to fads and fashions. Project Management is no exception. The issue of interest for this paper is the establishment of the 'College of Complex Project Managers' and their 'competency standard for complex project managers.' Both have generated significant interest in the Project Management community, and like any other human endeavour they should be subject to critical evaluation. The results of this evaluation show significant flaws in the definition of complex in this case, the process by which the College and its standard have emerged, and the content of the standard. However, there is a significant case for a portfolio of research that extends the existing bodies of knowledge into large-scale complicated (or major) projects that would be owned by the relevant practitioner communities, rather than focused on one organization. Research questions are proposed that would commence this stream of activity towards an intelligent synthesis of what is required to manage in both complicated and truly complex environments.

Synthesis, structure and magnetism of the oxalato-bridged chromium(III) complex [NBu4n](4)[Cr-2(ox)(5)]center dot 2CHCl(3)

The binuclear complex [NBu4n](4)[Cr-2(ox)(5)]. 2CHCl(3) has been prepared by an ion-exchange procedure employing Dowex 50WX2 cation-exchange resin in the n-butylammonium form and potassium tris(oxalato)chromate(III). The dimeric complex was characterised by a crystal structure determination: monoclinic, space group C2/c, a = 29.241(7), b = 15.192(2), c = 22.026(5) Angstrom, beta = 94.07(1)degrees, Z = 4. The magnetic susceptibility (300-4.2 K) indicated that the chromium(III) sites were antiferromagnetically coupled (J = -3.1 cm(-1)).

Carrageenans with complex substitution patterns from red algae of the genus Erythroclonium

Extracellular polysaccharides from three Erythroclonium spp. were shown, by a combination of compositional, linkage analyses, and Fourier transform infrared and C-13-nuclear magnetic resonance spectroscopy, to be highly substituted carrageenans with at least five types of repeating disaccharide units. These are the carrabiose 2,4'-disulfate of iota-carrageenan, carrabiose 2-sulfate of alpha-carrageenan, the 6'-O-methylated counterparts of each of these repeating units, and 4',6'-O-(1-carboxyethylidene)carrabiose 2-sulfate. The polysaccharides also contain significant amounts of unsubstituted, 4-linked galactopyranose and small amounts of 4-linked 3-O-methylgalactopyranose and terminal glycosyl residues. The carrageenan preparations of the three species are similar, differing only in the proportions of some components. (C) 1998 Elsevier Science Ltd.

A novel tricopper(II) complex of a polyamine alcohol

The trinuclear copper(II) complex of a new polyamino alcohol ligand has been isolated; it exhibits a structure similar to that found at the active site of ascorbate oxidase.

Lemon oil to beta-cyclodextrin ratio effect on the inclusion efficiency of beta-cyclodextrin and the retention of oil volatiles in the complex

Microencapsulation of lemon oil was undertaken with beta-cyclodextrin using a precipitation method at the five lemon oil to beta-cyclodextrin ratios of 3:97, 6:94, 9:91, 12:88, and 15:85 (w/w) in order to determine the effect of the ratio of lemon oil to beta-cyclodextrin on the inclusion efficiency of beta-cyclodextrin for encapsulating oil volatiles. The retention of lemon oil volatiles reached a maximum at the lemon oil to beta-cyclodextrin ratio of 6:94; however, the maximum inclusion capacity of beta-cyclodextrin and a maximum powder recovery were achieved at the ratio of 12:88, in which the beta-cyclodextrin complex contained 9.68% (w/w) lemon oil. The profile and proportion of selected flavor compounds in the beta-cyclodextrin complex and the starting lemon oil were not significantly different.

Targeting of a cholecystokinin-DNA complex to pancreatic cells in vitro and in vivo

The carboxy terminal octapeptide of cholecystokinin (CCK8) is a hormone that binds high affinity receptors in a number of tissues including pancreas and pancreatic tumours. As part of our studies to develop effective gene therapy for the treatment of pancreatic cancers, we have investigated various gene delivery systems that depend on CCK8 receptor targeting. In this paper,we describe the synthesis of a CCK8-DNA complex designed to deliver foreign DNA to cholecystokinin receptor-positive cells. CCK8 was ligated to avidin and then complexed to linearis biotinylated DNA (pSV-CAT). The uptake of P-32-labelled CCK8-DNA complex by rat pancreatic acini was linear with time over 4 h with 65-70% of uptake inhibited by 100 nM CCK8. The complex appeared to be internalised since it could not be removed by acid wash. When administered intra-arterially, the complex was rapidly removed from the circulation with no evidence of targeted delivery to the pancreas, However, following a single intraperitoneal dose, the pancreas accumulated-5- 8% of the total administered complex by 24 h. These results suggest that peptide-dependent gene delivery to CCK receptor positive cells in vivo is feasible but, when administered directly into the circulation, diffusional barriers across the endothelium may limit distribution to peripheral tissues. Intraperitoneal administration therefore may be a useful alternative for targeting the pancreas.

The metal directed assembly of a trinuclear macrocyclic copper(II) complex

A trinuclear macrocyclic complex is reported from the metal directed condensation between melamine, formaldehyde and the Cu-II complex of a linear tetraamine.

The first structurally characterized discrete dinuclear mu-cyano hexacyanoferrate complex

Mixed valence complexes containing ferro- and ferricyanide have been known for almost 300 years, but no dinuclear, non-polymeric examples of these complexes have been structurally characterized. Here we report the first such example, comprising ferrocyanide coordinated to a pentaaminecobalt(III) complex. This Fe-II-Co-III complex may be reversibly oxidized to the Fe-III-Co-III analogue.

Targeting local tissues by transdermal application: Understanding drug physicochemical properties that best exploit protein binding and blood flow effects

The targeting of topically applied drug molecules into tissues below a site of application requires an understanding of the complex interrelationships between the drug, its formulation, the barrier properties of the skin, and the physiological processes occurring below the skin that are responsible for drug clearance from the site, tissue, and/or systemic distribution and eventual elimination. There is still a certain amount of controversy over the ability of topically applied drugs to penetrate into deeper tissues by diffusion or whether this occurs by redistribution in the systemic circulation. The major focus of our work in this area has been in determining how changes in drug structure and physicochemical properties, such as protein binding and lipophilicity, affect drug clearance into the local dermal microcirculation and lymphatics, as well as subsequent distribution into deeper tissues below an application site. The present study outlines our recent thinking on the drug molecule optimal physical attributes, in terms of plasma and tissue partitioning behaviour, that offer the greatest potential for deep tissue targeting. Drug Dev. Res. 46:309-315, 1999. (C) 1999 Wiley-Liss, Inc.

Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with anti-tumour activity

Previous studies have demonstrated that 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and several other aroylhydrazone chelators possess anti-neoplastic activity due to their ability to bind intracellular iron. In this study we have examined the structure and properties of NIH and its Fe-III complex in order to obtain further insight into its anti-tumour activity. Two tridentate NIH ligands deprotonate upon coordination to Fe-III in a meridional fashion to form a distorted octahedral, high-spin complex. Solution electrochemistry of [Fe(NIH-H)(2)](+) shows that the trivalent oxidation state is dominant over a wide potential range and that the Fe-II analogue is not a stable form of this complex. The fact that [Fe(NIH-H)(2)](+) cannot-cycle between the Fe-II and Fe-III states suggests that the production of toxic free- radical species, e.g. OH. or O2(.-),is not part of this ligand's cytotoxic action. This suggestion is supported by cell culture experiments demonstrating that the addition of Fe-III to NIH prevents its anti-proliferative effect. The chemistry of this chelator and its Fe-III complex are discussed in the context of understanding its anti-tumour activity.

m144, a murine cytomegalovirus (MCMV)-encoded major histocompatibility complex class I homologue, confers tumor resistance to natural killer cell-mediated rejection

Until now, it has been unclear whether murine cytomegalovirus (MCMV)-encoded protein m144 directly regulates natural killer (NK) cell effector function and whether the effects of m144 are only strictly evident in the context of MCMV infection. We have generated clones of the transporter associated with antigen processing (TAP)-2-deficient RMA-S T lymphoma cell line and its parent cell line, RMA, that stably express significant and equivalent levels of m144. In vivo NK cell-mediated rejection of RMA-S-m144 lymphomas was reduced compared with rejection of parental or mock-transfected RMA-S clones, indicating the ability of m144 to regulate NK cell-mediated responses in vivo. Significantly, the accumulation of NK cells in the peritoneum was reduced in mice challenged with RMA-S-m144, as was the lytic activity of NK cells recovered from the peritoneum. Expression of m144 on RMA-S cells also conferred resistance to cytotoxicity mediated in vitro by interleukin 2-activated adherent spleen NK cells. In summary, the data demonstrate that m144 confers some protection from NK cell effector function mediated in the absence of target cell class I expression, but that in vivo the major effect of m144 is to regulate NK cell accumulation and activation at the site of immune challenge.

Metal-centred versus ligand-centred luminescence quenching of a macrocyclic copper(II) complex

The new macrocyclic ligand trans-6-(9-anthracenylmethylamino)-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecan-13-amine has been synthesized and characterised as its copper(II) complex and the crystal structure of this complex has been determined. Fluorescence of the anthracenyl group of the macrocycle is quenched in its free base form and when complexed with Cu-II. Fluorescence returns when Lewis acids such as H+ and Zn-II are added to solutions of the ligand, indicating that photoinduced electron transfer from the amine lone pairs is responsible for fluorescence quenching in the free base form. By contrast, fluorescence of the complex is quenched by intramolecular electronic energy transfer.

Synthesis of [Cu-2(Me-2[9]aneN(2)S)(2)(OH)(2)] (PF6)(2), a hydroxo-bridged copper(II) complex of N,N '-dimethyl-1-thia-4,7-diazacyclononane (Me-2[9]aneN(2)S). X-ray structural analysis, magnetic susceptibility, EPR and visible spectroscopy

The bis(mu-hydroxo) complex [Cu-2(Me-2[9]aneN(2)S)(2)(OH)(2)](PF6)(2) (Me-2[9]aneN(2)S = N,N'-dimethyl-1-thia-4,7-diazacyclononane) results after reaction of [Cu(Me-2[9]aneN(2)S)(MeCN)] (PF6) with dioxygen at -78 degrees C in acetonitrile. The complex has been characterized by X-ray crystallography: orthorhombic, space group Pnma, with a 18.710(3), b 16.758(2), c 9.593(2) Angstrom, and Z = 4. The structure refined to a final R value of 0.051. The complex contains two copper(II) ions bridged by two hydroxo groups with Cu ... Cu 2.866(1) Angstrom. The solid-state magnetic susceptibility study reveals ferromagnetic coupling, the fitting parameters being J = +46+/-5 cm(-1), g = 2.01+/-0.01 and theta = -0.58+/-0.03 K. The frozen-solution e.p.r. spectrum in dimethyl sulfoxide is characteristic of a monomeric copper(II) ion (g(parallel to) 2.300, g(perpendicular to) 2.063; A(parallel to) 156.2 x 10(-4) cm(-1), A(perpendicular to) 9.0 x 10(-4) cm(-1)) with an N2O2 donor set. Thioether coordination to the copper(II) in solution is supported by the presence of an intense absorption assigned to a sigma(S)-->Cu-II LMCT transition at c. 34000 cm(-1). The single-crystal spectrum of [Cu-2(Me-2[9]aneN(2)S)(2)(OH)(2)] (PF6)(2) (273 K) reveals d-->d transitions at 14500 and 18300 cm(-1) and a weak pi(S)-->Cu-II charge-transfer band at approximately 25000 cm(-1).

Th structure of the P-II-ATP complex

P-II is a signal transduction protein that is part of the cellular machinery used by many bacteria to regulate the activity of glutamine synthetase and the transcription of its gene. The structure of P-II was solved using a hexagonal crystal form (form I). The more physiologically relevant form of P-II is a complex with small molecule effecters. We describe the structure of P-II with ATP obtained by analysis of two different crystal forms (forms II and III) that were obtained by co-crystallization of P-II with ATP. Both structures have a disordered recognition (T) loop and show differences at their C termini. Comparison of these structures with the form I protein reveals changes that occur on binding ATP. Surprisingly, the structure of the P-II/ATP complex differs with that of GlnK, a functional homologue. The two proteins bind the base and sugar of ATP in a similar manner but show differences in the way that they interact with the phosphates. The differences in structure could account for the differences in their activities, and these have been attributed to a difference in sequence at position 82. It has been demonstrated recently that P-II and GlnK form functional heterotrimers in vivo. We construct models of the heterotrimers and examine the junction between the subunits.