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A number of conformations of cyclododecane, 12-crown-4 and its sulphur analogue have been generated from various sources. Molecular mechanics energy minimisation has been performed on each, using various schemes for representing the charge and dipole interactions. Changing the representation has a negligible effect on the energies and conformations of cyclododecane, changes only the absolute energies in 12-crown-4, but produces a reordering of the energies in the sulphur analogue. It is suggested that this is principally due to differences in the bond length to the heteroatom. Calculations on related crowns predict an odd-membered macrocycle to have higher energy than an even-membered system of greater ring size. more...

An NIH grant to the last three authors (IMH, SMP and PAY) was incorrectly omitted from the Funding Statement. The number of the grant is: EY022063-01.

Background Retinal vasculopathies, including diabetic retinopathy (DR), threaten the vision of over 100 million people. Retinal pericytes are critical for microvascular control, supporting retinal endothelial cells via direct contact and paracrine mechanisms. With pericyte death or loss, endothelial dysfunction ensues, resulting in hypoxic insult, pathologic angiogenesis, and ultimately blindness. Adipose-derived stem cells (ASCs) differentiate into pericytes, suggesting they may be useful as a protective and regenerative cellular therapy for retinal vascular disease. In this study, we examine the ability of ASCs to differentiate into pericytes that can stabilize retinal vessels in multiple pre-clinical models of retinal vasculopathy. Methodology/Principal Findings We found that ASCs express pericyte-specific markers in vitro. When injected intravitreally into the murine eye subjected to oxygen-induced retinopathy (OIR), ASCs were capable of migrating to and integrating with the retinal vasculature. Integrated ASCs maintained marker expression and pericyte-like morphology in vivo for at least 2 months. ASCs injected after OIR vessel destabilization and ablation enhanced vessel regrowth (16% reduction in avascular area). ASCs injected intravitreally before OIR vessel destabilization prevented retinal capillary dropout (53% reduction). Treatment of ASCs with transforming growth factor beta (TGF-β1) enhanced hASC pericyte function, in a manner similar to native retinal pericytes, with increased marker expression of smooth muscle actin, cellular contractility, endothelial stabilization, and microvascular protection in OIR. Finally, injected ASCs prevented capillary loss in the diabetic retinopathic Akimba mouse (79% reduction 2 months after injection). Conclusions/Significance ASC-derived pericytes can integrate with retinal vasculature, adopting both pericyte morphology and marker expression, and provide functional vascular protection in multiple murine models of retinal vasculopathy. The pericyte phenotype demonstrated by ASCs is enhanced with TGF-β1 treatment, as seen with native retinal pericytes. ASCs may represent an innovative cellular therapy for protection against and repair of DR and other retinal vascular diseases. more...

Objective To examine disparities in the receipt of preventive care recommended by the American Diabetes Association (ADA) between Appalachian and non-Appalachian counties and within Appalachian counties. Research design and methods Behavioral Risk Factor Surveillance System (BRFSS) data for 2008–2010 were used to identify individuals with diabetes and their preventive care usage. Each Appalachian respondent county of residence was categorised into one of the five economic levels: distressed, at-risk, transitional, competitive and attainment counties. Competitive and attainment counties were combined and designated as competitive counties. We used logistic regressions to compare receipt of ADA preventive care recommendations by county economic level, adjusting for respondent demographic, socioeconomic, health and access-to-care factors. Results Compared to the most affluent (competitive) counties, less affluent (distressed and at-risk) counties demonstrated equivalent or higher rates of self-care practices such as daily blood glucose monitoring and daily foot checks. But they showed 40–50% lower uptake of annual foot and eye examinations and 30% lower uptake of diabetes education and pneumococcal vaccinations compared to competitive counties. After adjusting for demographic factors, significant disparities still existed in the uptake of annual foot examinations, annual eye examinations, 2 or more A1c tests per year and pneumococcal vaccinations in distressed and at-risk counties compared to competitive counties. Appalachian counties as a whole were similar to non-Appalachian counties in the uptake of all recommendations with the absolute differences of ≤3%. Conclusions Our results show that there are significant disparities in the uptake of many recommended preventive services between less and more affluent counties in the Appalachian region. more...

A number of 1- and 3-hydroxy and 1-amino substituted acyclic pentadienyl cations have been characterised by NMR spectroscopy in situ at low temperature. Some of the 3-hydroxy cations undergo cyclisation to give 1-hydroxycyclopentenyl cations which on deprotonation give substituted cyclopentenones. more...

Molecular mechanics and semi-empirical AM1 molecular orbital calculations have been performed on a series of 1 H ,3 H -thiazolo[3,4- a ]benzimidazoles which are known to have anti-HIV activity. Different substituents in the 2′ and 3′ positions are found to have a minimal effect on the basic structure of the compounds, with only bond angles showing any significant variation. Differences in the electronic properties are more marked, and are more likely to be responsible for the differences in activity and toxicity of the compounds that are found experimentally. more...

Modified Neglect of Differential Overlap molecular orbital calculations have been performed on the dyes neutral red, acridine orange, proflavine, azure B, methylene blue and thionine. The presence of sulphur in the ring system of the last three appears to be responsible for most of the variations in geometry and charge distribution between the two groups, but there are some differences which cannot be explained in this way. These include a spread of dipole moment values and variations in the geometry around nitrogen atoms outside the ring system. more...

Metal complexes form an important class of potential antiviral agents, but are less amenable to modelling studies than their organic counterparts. Molecular mechanics calculations on a series of palladium and palladium chloride complexes with the ligands 2-aminopyridine, 2,3-diaminopyridine, 2,6-diaminopyridine, 2-amino-4-methylpyridine and benzonitrile have been performed using zero partial charges, partial charges with the in vacuo dielectric constant and partial charges with the dielectric constant of water. The resulting geometries exhibit more marked differences in the relative orientation of the ligand rings than in the coordination sphere. Semiempirical molecular orbital calculations on the free ligands confirm the experimentally observed mode of coordination when the MNDO or PM3 hamiltonians are used, but not with AM1. more...

The steric energies of a number of the conformations of thymidine, derived from appropriate crystal structures, have been determined with the MM2 molecular mechanics force field. With one exception, these have very similar values which are close to 120 kJ mol−1. The C2′-exo/C3′-endo conformation has a far higher value of 240 kJ mol−1. The C3′-endo conformation has previously been associated with thymidine derivatives which do not exhibit anti-HIV activity, and it may be that this is due to the relatively low predicted stability. more...

Geometry optimisation calculations using semiempirical molecular orbital and molecular mechanics methods on tetrahedral zinc complexes with derivatives of the amino acids cysteine, histidine and glutamic acid have been performed. Charge interaction terms, based on a semiempirical calculation of partial atomic charges, are found to dominate the molecular mechanical steric energy. Geometries optimised by molecular mechanics show better agreement with crystallographic results than do those obtained by the modified neglect of differential overlap method. The final steric energy values show a large variation between the complexes of the derivatives of cysteine, histidine and glutamic acid. more...

Cyclic and acyclic thymidine analogues may act as anti-human immunodeficiency virus agents. Several structures have been optimized using molecular mechanics, and electronic properties calculated using the modified neglect of differential overlap method. Introduction of an unsaturated bond into the ribose ring leads to a large increase in strain energy, but the quantum mechanical heat of formation remains reasonable. Electrostatic potentials were calculated based on partial atomic charges, and compared with the potential around thymidine. It is found that a common region of positive potential exists in the C3' region for the active compounds, and on this basis the unsynthesized acyclic compounds studied here may be active. In azidothymidine (AZT) the extent of twist around the N1-C1' bond determines the presence or absence of this feature. A relationship is found to exist between the molecular mechanics energy and the EC50 activity data for the azido-substituted compounds. more...

The benzothiazole derivatives reported here have structural similarities to the 2-phenylindole derivatives that are known to bind to oestrogen receptors. We report the synthesis of 5,6-dimethoxy-2-(4-methoxyphenyl)- benzothiazole together with the determination of its three dimensional crystal structure. Crystals are monoclinic, space group P21/c, a=17.142(1), b=11.165(1), c=7.683(2)A, β=101.34(1)°. 2307 Reflections were refined to R=0.039. The inter-ring twist angle is 21°, greater than in 2-(o-hydroxyphenyl)benzothiazole but similar to that in 2-(4′-bromophenyl)-4,6-dimethoxyindole. Molecular mechanics calculations predict a torsional barrier to inter-ring twist of 6.3 kcal mol−1 for unsubstituted benzothiazole. Molecular orbital calculations show that while hydrogen bonding can confer stability on substituted benzothiazoles, a greater number of non-hydrogen bonding groups as substituents can confer even greater stability. more...

Variable temperature NMR studies have established equilibrium constants and/or activation parameters for the exo2↔exo3 equilibrium in the series M(o-tolyl)3(M = P, As), XM (o-tolyl)3(M = P, X = O, S, Se; M = As, X = O, S) and [MeM(o-tolyl)3]n+(n= 0, M = Si; n= 1, M = P, As). The crystal structure of OAs(o-tolyl)3H2O is reported. Molecular mechanics studies of P(o-tolyl)3 reproduce correctly the ground state exo3 conformation and provide an analysis of the lowest energy two-ring flip exchange mechanism. more...

The site of alkylation of triazolopyridines ( 1 a ), ( 5 ), and ( 6 ) has been interpreted using semi-empirical and ab initio molecular orbital calculations. Attack by hydride on the methyl triazolopyridinium salt ( 3a ) has been shown to give the triazolylbutadiene ( 4a ), while the isomeric salt ( 2a ) is unaffected by nucleophiles. These observations are interpreted by consideration of the mechanisms of reaction, and calculation of appropriate energy levels. more...

Currently, little is known about the response of the adult retinal microvasculature to hypoxia. To test the hypothesis that chronic systemic hypoxia induces angiogenesis and microvascular remodeling in the adult mouse retina, adult 10-week old female C57Bl/6 mice were exposed to 10% O(2) for 2 or 3 weeks. After hypoxia exposure, retinas were harvested, whole-mounted, and processed for immunohistochemistry. Retinas were stained with lectin, anti-smooth muscle alpha-actin antibody, and anti-NG2 antibody to visualize microvascular networks and their cellular components. Confocal microscopy was used to obtain images of superficial retinal networks. Images were analyzed to assess vessel diameter, vascular length density, branch point density, and the presence of vascular loops, a hallmark of intussusceptive angiogenesis. Both 2 and 3 weeks of hypoxia exposure resulted in a significant increase in the diameters of arterioles and post-arteriole capillaries (p0.003). After 3 weeks of hypoxia, vascular length density and branch point density were significantly increased in retinas exposed to hypoxia as compared to normoxic controls (p0.001). The number of vascular loops in the superficial retinal networks was significantly greater in hypoxia-exposed retinas (por = 0.001). Our results demonstrate, for the first time, intussusceptive angiogenesis as a tissue-level mechanism of vascular adaptation to chronic systemic hypoxia in the adult mouse retina and contribute to our understanding of hypoxia-induced angiogenesis and microvascular remodeling in the adult animal. more...

The geometries of thymidine and its iodo-, bromo-, fluoro- and trifluoro-methylene derivatives were optimised using molecular mechanics force field methods. The CF 3 substituted compound shows extreme values of many geometrical parameters with respect to the others, and a slight rotation of this group is seen with respect to the orientation of CH 3 in thymidine. The van der Waals volumes of thymidine and this derivative are very similar, although this is not the case for their steric energies. Subsequent ab initio molecular orbital calculations showed that the different substituents on C5 lead to significant differences in the partial atomic charges on C4 and C6, but have little effect on N1 and N3. The effect of an inter-ring twist may also contribute to the slight charge variation seen on N1. more...

Several starting conformations of tricyclodecane and the anti-viral agents amantadine, rimantadine and 1-adamantylguanidine were optimised using both molecular mechanics (MM2) and the semi-empirical molecular orbital (MNDO) method. In the former case, electronic properties were subsequently calculated using the ab initio molecular orbital method ( gaussian 86 ). Despite being symmetrically equivalent, the different starting conformations of rimantadine and 1-adamantylguanidine converge to slightly different stericenergy and heat-of-formation values. Partial atomic charges on the carbon atoms in tricyclodecane are predicted to be −0.030 ( gaussian 86 ) or −0.056 (MNDO) for the bridgehead atoms and −0.096 (GAUSSIAN 86) or 0.009 (MNDO) for the others. The gaussian 86 predicted charges on the central atom of the substituent group are most positive for the least active compound (1-adamantylguanidine). There are small differences in geometry and charge distribution between equivalent conformations and between the two sets of calculations. more...

Cyclic and acyclic thymidine analogues may act as anti-human immunodeficiency virus agents. Several structures have been optimized using molecular mechanics, and electronic properties calculated using the modified neglect of differential overlap method. Introduction of an unsaturated bond into the ribose ring leads to a large increase in strain energy, but the quantum mechanical heat of formation remains reasonable. Electrostatic potentials were calculated based on partial atomic charges, and compared with the potential around thymidine. It is found that a common region of positive potential exists in the C3' region for the active compounds, and on this basis the unsynthesized acyclic compounds studied here may be active. In azidothymidine (AZT) the extent of twist around the N1-C1' bond determines the presence or absence of this feature. A relationship is found to exist between the molecular mechanics energy and the EC50 activity data for the azido-substituted compounds. more...

The benzothiazole derivatives reported here have structural similarities to the 2-phenylindole derivatives that are known to bind to oestrogen receptors. We report the synthesis of 5,6-dimethoxy-2-(4-methoxyphenyl)- benzothiazole together with the determination of its three dimensional crystal structure. Crystals are monoclinic, space group P21/c, a=17.142(1), b=11.165(1), c=7.683(2)A, β=101.34(1)°. 2307 Reflections were refined to R=0.039. The inter-ring twist angle is 21°, greater than in 2-(o-hydroxyphenyl)benzothiazole but similar to that in 2-(4′-bromophenyl)-4,6-dimethoxyindole. Molecular mechanics calculations predict a torsional barrier to inter-ring twist of 6.3 kcal mol−1 for unsubstituted benzothiazole. Molecular orbital calculations show that while hydrogen bonding can confer stability on substituted benzothiazoles, a greater number of non-hydrogen bonding groups as substituents can confer even greater stability. more...

Using a set of macrocyclic ligands 8,12;21,25-dinitrilo-1,6,14,19-tetra-azacyclohexacosa-1 (26),6,8,10,13,19,22,24-octaene (L1), 7,11; 19,23-dinitrilo-1,5,13,17-tetra-azacyclotetracosa-1 (24),5,7,9,12,17,20,22-octaene (L2), and 7,10;18,21 -diepoxy-1,5,12,16-tetra-azacyclodecosa-1 (22),5,7,9,11,16,18,20-octaene (L3), NCS bridged binuclear complexes of all five members of the first transition series from MnII to CuII have been obtained. The observation of strong i.r. absorption below 2 000 cm–1 shows that the NCS– ligand adopts the rare NCS bridging mode in binuclear tetrakis- or bis-(thiocyanato) complexes of MnII, FeII, CoII, and NiII with the ligand L1 and in complexes of CoII and NiII with L2. With L3, a NCS-N link between copper(II) ions is seen, the first observation of a truly symmetric Cu–N(CS)–Cu assembly. These structures have been investigated by molecular mechanics which confirms that the steric constraints of the macrocycles are responsible for the structure variations. Magnetic susceptibility measurements show that the NCS-N bridge is a poor mediator of magnetic interaction between paramagnetic centres, as compared with N3–-N or OH– links. The structures of the precursor compounds [BaL1(ClO4)2] and [BaL2(ClO4)2]·EtOH have been determined by X-ray crystallography. more...

A molecular mechanics force field has been developed which accurately reproduces experimental solid state structures and conformer interconversion barriers for a series of sterically congested diaryl and triaryl phosphines and some of their chalcogenide and Cr(CO)5 derivatives. more...

The topographic projection of retinal ganglion cell (RGC) axons to mouse superior colliculus (SC) or chick optic tectum (OT) is formed in three phases: RGC axons overshoot their termination zone (TZ); they exhibit interstitial branching along the axon that is topographically biased for the correct location of their future TZ; and branches arborize preferentially at the TZ and the initial exuberant projection refines through axon and branch elimination to generate a precise retinotopic map. We present a computational model of map development that demonstrates that the countergradients of EphAs and ephrinAs in retina and the OT/SC and bidirectional repellent signaling between RGC axons and OT/SC cells are sufficient to direct an initial topographic bias in RGC axon branching. Our model also suggests that a proposed repellent action of EphAs/ephrinAs present on RGC branches and arbors added to that of EphAs/ephrinAs expressed by OT/SC cells is required to progressively restrict branching and arborization to topographically correct locations and eliminate axon overshoot. Simulations show that this molecular framework alone can develop considerable topographic order and refinement, including axon elimination, a feature not programmed into the model. Generating a refined map with a condensed TZ as in vivo requires an additional parameter that enhances branch formation along an RGC axon near sites that it has a higher branch density, and resembles an assumed role for patterned neural activity. The same computational model generates the phenotypes reported in ephrinA deficient mice and Isl2-EphA3 knockin mice. This modeling suggests that gradients of counter-repellents can establish a substantial degree of topographic order in the OT/SC, and that repellents present on RGC axon branches and arbors make a substantial contribution to map refinement. However, competitive interactions between RGC axons that enhance the probability of continued local branching are required to generate precise retinotopy. more...

We report that the EphB receptor ligand, ephrin-B1, may act bifunctionally as both a branch repellent and attractant to control the unique mechanisms in mapping the dorsal-ventral (DV) retinal axis along the lateral-medial (LM)axis of the optic tectum. EphB receptors are expressed in a low to high DV gradient by retinal ganglion cells (RGCs), and ephrin-B1 is expressed in a low to high LM gradient in the tectum. RGC axons lack DV ordering along the LM tectal axis, but directionally extend interstitial branches that establish retinotopically ordered arbors. Recent studies show that ephrin-B1 acts as an attractant in DV mapping and in controlling directional branch extension. Modeling indicates that proper DV mapping requires that this attractant activity cooperates with a repellent activity in a gradient that mimics ephrin-B1. We show that ectopic domains of high, graded ephrin-B1 expression created by retroviral transfection repel interstitial branches of RGC axons and redirect their extension along the LM tectal axis, away from their proper termination zones (TZs). In contrast, the primary RGC axons are unaffected and extend through the ectopic domains of ephrin-B1 and arborize at the topographically correct site. However, when the location of a TZ is coincident with ectopic domains of ephrin-B1, the domains appear to inhibit arborization and shape the distribution of arbors. Our findings indicate that ephrin-B1 selectively controls, through either attraction or repulsion, the directional extension and arborization of interstitial branches extended by RGC axons arising from the same DV position: branches that arise from axons positioned lateral to the correct TZ are attracted up the gradient of ephrin-B1 and branches that arise from axons positioned medial to the same TZ are repelled down the ephrin-B1 gradient. Alternatively, EphB receptor signaling may act as a `ligand-density sensor' and titrate signaling pathways that promote branch extension toward an optimal ephrin-B1 concentration found at the TZ; branches located either medial or lateral to the TZ would encounter a gradient of increasingly favored attachment in the direction of the TZ. more...

PURPOSE To construct a low-cost, easy-to-use, high-image-quality mydriatic fundus camera with "point-and-shoot" operation, and to evaluate the efficacy of this camera to accurately document retinal disease. METHODS A prototype portable fundus camera was designed by interfacing a novel optical module with a Panasonic Lumix G2 consumer camera. Low-cost, commercially available optics were used to create even illumination of the fundus, providing a 50° retinal field of view. A comparative study assessing the image quality of the prototype camera against a traditional tabletop fundus camera was conducted under an Institutional Review Board (IRB)-approved study. RESULTS A stand-alone, mydriatic camera prototype was successfully developed at a parts cost of less than $1000. The prototype camera was capable of operating in a point-and-shoot manner with automated image focusing and exposure, and the image quality of fundus photos was comparable to that of existing commercial cameras. Pathology related to both nonproliferative and proliferative diabetic retinopathy and age-related macular degeneration was easily identified from fundus images obtained from the low-cost camera. CONCLUSIONS Early prototype development and clinical testing have shown that a consumer digital camera can be inexpensively modified to image the fundus with professional diagnostic quality. The combination of low cost, portability, point-and-shoot operation, and high image quality provides a foundational platform on which one can design an accessible fundus camera to screen for eye disease. more...

PURPOSE EphB4 and ephrinB2 are known key regulators of retinal vascular development, but due to their capacity for bidirectional signaling, delineation of their individual roles in this process remains unclear. To better dissect out individual contributions, a model of proliferative retinopathy in mice with attenuated ephrinB2 reverse signaling was studied. It was hypothesized that endothelial ephrinB2 reverse signaling regulates hypoxia-induced capillary sprouting, as well as the pathologic formation of neovascular tufts in postnatal retinal microvascular networks. METHODS Genetically manipulated mice with attenuated ephrinB2 reverse signaling (ephrinB2(lacZ/+)), along with wild-type (WT) controls, were exposed to oxygen-induced retinopathy (OIR), a postnatal model of proliferative retinopathy. At peak disease (postnatal day 18), microvascular networks were analyzed to examine intraretinal revascularization, capillary sprouting, and pathologic neovascularization responses. EphB4 and phosphorylated ephrinB protein expression patterns along retinal microvessels were also assessed. RESULTS EphrinB2(lacZ/+) mice exhibited reduced hypoxia-induced revascularization (P ≤ 0.04) and reduced formation of neovascular tufts (P < 0.001), as compared with WT controls. Corresponding to the observed inhibition of retinal angiogenesis, ephrinB2(lacZ/+) retinas displayed an increased number of blind-ended capillary sprout tips (P < 0.02) and endothelial filopodial processes (P = 0.001). In WT and ephrinB2(lacZ/+) OIR-exposed retinas, ephrinB was confined to endothelial cells, with expression detected along angiogenic vascular processes including neovascular tufts and blind-ended capillary sprouts. CONCLUSIONS EphrinB2 reverse signaling is a regulator of key processes during retinal vascularization and controls pathologic retinal angiogenesis through direct effects on capillary sprouting and endothelial filopodia formation. more...

Using a set of macrocyclic ligands 8,12;21,25-dinitrilo-1,6,14,19-tetra-azacyclohexacosa-1 (26),6,8,10,13,19,22,24-octaene (L1), 7,11; 19,23-dinitrilo-1,5,13,17-tetra-azacyclotetracosa-1 (24),5,7,9,12,17,20,22-octaene (L2), and 7,10;18,21 -diepoxy-1,5,12,16-tetra-azacyclodecosa-1 (22),5,7,9,11,16,18,20-octaene (L3), NCS bridged binuclear complexes of all five members of the first transition series from MnII to CuII have been obtained. The observation of strong i.r. absorption below 2 000 cm–1 shows that the NCS– ligand adopts the rare NCS bridging mode in binuclear tetrakis- or bis-(thiocyanato) complexes of MnII, FeII, CoII, and NiII with the ligand L1 and in complexes of CoII and NiII with L2. With L3, a NCS-N link between copper(II) ions is seen, the first observation of a truly symmetric Cu–N(CS)–Cu assembly. These structures have been investigated by molecular mechanics which confirms that the steric constraints of the macrocycles are responsible for the structure variations. Magnetic susceptibility measurements show that the NCS-N bridge is a poor mediator of magnetic interaction between paramagnetic centres, as compared with N3–-N or OH– links. The structures of the precursor compounds [BaL1(ClO4)2] and [BaL2(ClO4)2]·EtOH have been determined by X-ray crystallography. more...

A simple source of data for students to use in studying uncertainty analysis is a rectangle drawn by the instructor. Determination of lengths, perimeter, and area can be used to illustrate statistical methods and the propagation of error theorem. The effort and equipment involved are minimal, making this technique ideal for use in a non-laboratory-based course. more...

The crystal structure of [Cr(CO)5{P(C6H4Me-o)3}] has been determined. It reveals an exo2 conformation for the phosphine ligand, in agreement with molecular mechanics calculations. Barriers to P–C rotation in the series [M(CO)5{P(C6H4Me-o)3}](M = Cr, Mo or W) are in the range 36–42 kJ mol–1; restricted M–P rotation is also evident in the low-temperature 13CO NMR spectrum of [Cr(CO)5{P(C6H4Me-o)3}]. The crystal structure of the π complex [Cr(CO)3{P(C6H4Me-o)}3] is most consistent with an electron-acceptor character for the P(C6H4Me-o)2 substituent. Crystal data: [Cr(CO)5{P(C6H4Me-o)3}], monoclinic, space group P21/n, a= 10.774(2), b= 14.951(5), c= 14.687(7)A, β= 91.45(2)°, Z= 4, R′= 0.0980 for 209 variable parameters and 2326 observed reflections; [Cr(CO)3{P(C6H4Me-o)3}], monoclinic, space group P21/a, a= 16.725(2), b= 7.340(1), c= 17.675(4), β= 92.66(2)°, Z= 4, R′= 0.1187 for 263 variable parameters and 1848 observed reflections. more...

Variable temperature NMR studies have established equilibrium constants and/or activation parameters for the exo2↔exo3 equilibrium in the series M(o-tolyl)3(M = P, As), XM (o-tolyl)3(M = P, X = O, S, Se; M = As, X = O, S) and [MeM(o-tolyl)3]n+(n= 0, M = Si; n= 1, M = P, As). The crystal structure of OAs(o-tolyl)3H2O is reported. Molecular mechanics studies of P(o-tolyl)3 reproduce correctly the ground state exo3 conformation and provide an analysis of the lowest energy two-ring flip exchange mechanism. more...

The crystal structures of the compounds [Cu2L1(NCMe)2][BPh4]21′, [Cu2L2(NCMe)2][ClO4]22 and [Cu2L3(NCMe)2][ClO4]23 have been determined {L1= 23,24-dioxa-3,7,14,18-tetraazatricyclo-[18.2.1.19,12]tetracosa-1(22),2,7,9,11,13,18,20-octaene, L2= 5,5,16,16-tetramethyl derivative of L1, L3= 23,24-dithia analogue of L1}. Complex 1′ is monoclinic, space group P21/n, Z= 2 with a= 10.45(1), b= 15.72(1), c= 18.08(1)A and β= 97.0(1)°, 2 is triclinic, space group P, Z= 1, with a= 7.447(8), b= 12.094(9), c= 10.731(9)A, α= 118.6(1), β= 78.8(1) and γ= 103.7(1)° and 3 is monoclinic, space group P21/c, Z= 2, with a= 8.15(1), b= 9.41(1), c= 19.35(2)A and β= 100.0(1)°; 1122, 1298 and 1071 reflections have been refined to R= 0.079, 0.055 and 0.072 respectively. All structures contain discrete cations and anions with the cations containing crystallographic centres of symmetry. In the cations the copper atoms are three-co-ordinate being bound to two nitrogen atoms of the macrocycle and one of an NCMe group in a pyramidal co-ordination sphere, Cu–N bond lengths ranging from 1.855(5) to 1.991(11)A. The Cu ⋯ S distances in 3 are 3.07(1) and 2.89(1)A indicating a fairly strong interaction. This distorts the planar part of the macrocycle and leads to a large Cu ⋯ Cu separation of 4.654(3)A. The corresponding value of 3.675(1)A in 2 is larger than that of 3.395(4)A in 1 due to repulsion between the additional methyl groups in L2. more...

Template condensation products of 1,5-diaminopentane and 1,6-diaminohexane with 2,6-diacetylpyridine on Pb(NCS)2 have been transmetallated with CoII and CuII to yield homobinuclear complexes of the 24- and 26-membered macrocycles, L1 and L2 respectively. In the dicobalt(II) complex of the smaller macrocycle, L1, a thermally populated spin equilibrium exists lying well to the low-spin side at 93 K. E.s.r. spectra indicate the complex has an equatorially compressed tetragonal geometry. The dicobalt(II) complex of the larger macrocycle, L2, is effectively high-spin, down to 93 K. Dicopper(II) complexes of L1 display a weak antiferromagnetic interaction, absent in analogous complexes of L2. Heterobinuclear complexes [PbML1(NCS)2(MeCN)2][ClO4]2 of the 24-membered macrocycle have been prepared for M = NiII and FeII, as confirmed by fast-atom bombardment (f.a.b.) mass spectra. An X-ray crystallographic structure determination on the heterobinuclear complex PbMnL1(NCS)4 reveals a Pb–Mn distance of 4.857(2)A and confirms that the metal centres are bridged by two 1,3-µ–NCS–bridges, as inferred from i.r. spectroscopy for the other thiocyanato complexes studied. However, the X-ray structure shows that in this case the thiocyanate bridges present both S-donors to Pb and both N-donors to Mn. more...

The crystal structure of the free macrocycle β-2,12-dimethyl-3,7,11,17-tetra-azabicyclo[11.3.1]heptadeca-1 (17),13,15-triene (L1) is reported. Crystals are monoclinic, space group P21/a, with a= 8.433(9), b= 23.697(12), c= 8.653(10)A, β= 113.9(1)°, and Z= 4. A total of 810 independent reflections above background have been refined to R 0.077. The free macrocycle has a folded shape very different from the conformation that is found in metal complexes. Empirical force-field methods have been used to calculate the steric energies of the various conformations of this ligand in the free state and in a series of nickel complexes, viz. [NiL1]2+, [NiL1(NO2)(ONO)], and [NiL1(en)]2+(en = ethylenediamine), and also to provide a hole-size profile for the macrocycle. more...

The techniques of molecular graphics and molecular mechanics have been used to investigate several different structural problems concerned with macrocycles. These include predictions of detailed molecular geometry; calculations of the llgoodness of fitt1 of a metal ion inside a particular macrocycle in terms of defined geometric and energetic parameters; interactions between macrocyclic complexes and other molecules; and specifically the positioning of solvent guests within the macrocycle. more...

A number of di-Cu(II) complexes of the new tetraimine macrocyclic ligand derived from the Schiff base [2 + 2] condensation of 2,5-diformylfuran with 3-oxa-pentane-1,5-diamine have been prepared by methods which employ the heavier alkaline earth metal ions as templates followed by transmetallation. The complexes have been characterised by spectroscopic and other physical methods. Several of the di-Cu(I) complexes react reversibly with CO in solution and irreversibly with O2 in a 4:1 Cu:O2 stoicheiometry. Depending on conditions the oxidation product may be a dinuclear Cu(II) complex of the macrocycle or a mononuclear Cu(II) complex of a new ring-opened ligand. The single crystal X-ray structure of the latter complex has been determined. [CuL](BPh4)2 is monoclinic, space group C2/c with a=20.12(1), b=14.48(1), c=22.37(2) A, β=110.1(1)°, Z=4. 1389 Independent reflections above background were measured on a diffractometer and the structure refined to R=0.108. The cation has imposed C2 symmetry. The copper atom is bonded to four nitrogen atoms in the ‘outer’ compartment of the ligand with unique CuN distances of 2.050(17) and 1.977(17) A. The geometry of the copper atom is intermediate between square planar and tetrahedral with an angle of 39.7° between two CuN2 planes. Molecular mechanics calculations show that this distortion is due to steric effects. more...

Contrary to previous reports, the Friedel–Crafts reaction between 3,4-dimethoxyphthalic anhydride and o-cresol gives a mixture of four benzoylbenzoic acids. After cyclisation and methylation, the major and minor products were 1,2,6- and 1,2,8-trimethoxy-7-methylanthraquinone respectively. The latter quinone and its demethylation product differ from cladofulvin trimethyl ether and cladofulvin respectively, thus indicating that the fungal pigment cladofulvin is not 1,2,8-trihydroxy-7-methylanthraquinone as was previously suggested. more...

The chromium complex is chemically bonded by ion exchange with alkali cations to strongly acidic sites in the glass surface. These sites are formed by the isomorphous replacement of silicon by boron and aluminum in the network structure. Polymerized complexes are better bonding agents than monomeric ones. Specific interactions between organic groups on the chrome complex and the bonding resins also determine laminate strength and water resistance. more...

Topographic maps are a fundamental feature of sensory representations in nervous systems. The formation of one such map, defined by the connection of ganglion cells in the retina to their targets in the superior colliculus of the midbrain, is thought to depend upon an interaction between complementary gradients of retinal EphA receptors and collicular ephrin-A ligands. We have tested this hypothesis by using gene targeting to elevate EphA receptor expression in a subset of mouse ganglion cells, thereby producing two intermingled ganglion cell populations that express distinct EphA receptor gradients. We find that these two populations form separate maps in the colliculus, which can be predicted as a function of the net EphA receptor level that a given ganglion cell expresses relative to its neighbors. more...

Axon pathfinding relies on the ability of the growth cone to detect and interpret guidance cues and to modulate cytoskeletal changes in response to these signals. We report that the murine POU domain transcription factor Brn-3.2 regulates pathfinding in retinal ganglion cell (RGC) axons at multiple points along their pathways and the establishment of topographic order in the superior colliculus. Using representational difference analysis, we identified Brn-3.2 gene targets likely to act on axon guidance at the levels of transcription, cell–cell interaction, and signal transduction, including the actin-binding LIM domain protein abLIM. We present evidence that abLIM plays a crucial role in RGC axon pathfinding, sharing functional similarity with its C. elegans homolog, UNC-115. Our findings provide insights into a Brn-3.2-directed hierarchical program linking signaling events to cytoskeletal changes required for axon pathfinding. more...