Self-Assembled Anion-Binding Cryptand for the Selective Liquid-Liquid Extraction of Phosphate Anions.

The ligands L1 and L2 form trinuclear self-assembled complexes with Cu2+ (i.e. [(L1 )2 Cu3 ]6+ or [(L2 )2 Cu3 ]6+ ) both of which act as a host to a variety of anions. Inclusion of long aliphatic chains on these ligands allows the assemblies to extract anions from aqueous media into organic solvents. Phosphate can be removed from water efficiently and highly selectively, even in the presence of other anions.

Self-Assembly of an Anion-Binding Cryptand for the Selective Encapsulation, Sequestration, and Precipitation of Phosphate from Aqueous Systems.

The self-assembled trimetallic species [L2 Cu3 ]6+ contains a cavity that acts as a host to many different anions. By using X-ray crystallography, ESI-MS, and UV/Vis spectroscopy we show that these anions are encapsulated both in the solid state and aqueous systems. Upon encapsulation, the anions Br- , I- , CO32- , SiF62- , IO63- , VO43- , WO42- , CrO42- , SO42- , AsO43- , and PO43- are all precipitated from aqueous solution and can be removed by filtration. Furthermore, the cavity can be tuned to be selective to either phosphate or sulfate anions by variation of the pH. Phosphate anions can be removed from water, even in the presence of other common anions, reducing the concentration from 1000 to <0.1 ppm and recovering approximately 99 % of the phosphate anions.

Ruthenium-Containing Linear Helicates and Mesocates with Tuneable p53-Selective Cytotoxicity in Colorectal Cancer Cells.

The ligands L1 and L2 both form separable dinuclear double-stranded helicate and mesocate complexes with RuII . In contrast to clinically approved platinates, the helicate isomer of [Ru2 (L1 )2 ]4+ was preferentially cytotoxic to isogenic cells (HCT116 p53-/- ), which lack the critical tumour suppressor gene. The mesocate isomer shows the reverse selectivity, with the achiral isomer being preferentially cytotoxic towards HCT116 p53+/+ . Other structurally similar RuII -containing dinuclear complexes showed very little cytotoxic activity. This study demonstrates that alterations in ligand or isomer can have profound effects on cytotoxicity towards cancer cells of different p53 status and suggests that selectivity can be "tuned" to either genotype. In the search for compounds that can target difficult-to-treat tumours that lack the p53 tumour suppressor gene, [Ru2 (L1 )2 ]4+ is a promising compound for further development.

Catalytic sp3 -sp3 Functionalisation of Sulfonamides: Late-Stage Modification of Drug-Like Molecules.

A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp3 -functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd0 catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.

Structural Strength Benefits Observed at the Hip of Premenarcheal Gymnasts Are Maintained Into Young Adulthood 10 Years After Retirement From the Sport.

PURPOSE: Premenarcheal female gymnasts have been consistently found to have greater bone mass and structural advantages. However, little is known about whether these structural advantages are maintained after the loading stimulus is removed. Therefore, the purpose of this study was to investigate the structural properties at the hip after long-term retirement from gymnastics. METHODS: Structural properties were derived from dual-energy X-ray absorptiometry scans using the hip structural analysis program for the same 24 gymnasts and 21 nongymnasts both in adolescence (8-15 y) and adulthood (22-30 y). Structural measures were obtained at the narrow neck, intertrochanter, and femoral shaft and included cross-sectional area, section modulus, and buckling ratio. Multivariate analysis of covariance was used to assess differences between groups in bone measures while controlling for size, age, maturity, and physical activity. RESULTS: Gymnasts were found to have structural advantages at the narrow neck in adolescence (16% greater cross-sectional area, 17% greater section modulus, and 25% lower buckling ratio) and 14 years later (13% greater cross-sectional area and 26% lower buckling ratio). Benefits were also found at the intertrochanter and femoral shaft sites in adolescence and adulthood. CONCLUSION: Ten years after retirement from gymnastics, former gymnasts' maintained significantly better hip bone structure than females who did not participate in gymnastics during growth.

Formation of a dimer of trinuclear helicates which encapsulates an array of six hydrogen-bonded anions.

The amine-containing ligand L, composed of two bidentate pyridyl-thiazole moieties linked by a 1,3-diaminophenylene unit, reacts with copper(II) ions to form a dinuclear double helicate [Cu2 L2 ](4+) . Reaction of [Cu2 L2 ](4+) with dihydrogen phosphate (0.5 equivalents) gives the unsaturated dinuclear double helicate [Cu2 L2 (OPO3 H2 )](3+) . [Cu2 L2 (OPO3 H2 )](3+) further reacts with another 0.5 equivalents of dihydrogen phosphate to give a trinuclear circular helicate which then self-assembles into a hexameric cluster [{Cu3 L3 (OPO3 H2 )3 }](26+) .

Self-assembly of an anion receptor with metal-dependent kinase inhibition and potent in vitro anti-cancer properties.

One topical area of supramolecular chemistry is the binding of anionic species but despite the importance of anions in diverse cellular processes and for cancer development, anion receptors or 'binders' have received little attention as potential anti-cancer therapeutics. Here we report self-assembling trimetallic cryptands (e.g. [L2(Metal)3]6+ where Metal = Cu2+, Zn2+ or Mn2+) which can encapsulate a range of anions and which show metal-dependent differences in chemical and biological reactivities. In cell studies, both [L2Cu3]6+ and [L2Zn3]6+ complexes are highly toxic to a range of human cancer cell lines and they show significant metal-dependent selective activity towards cancer cells compared to healthy, non-cancerous cells (by up to 2000-fold). The addition of different anions to the complexes (e.g. PO43-, SO42- or PhOPO32-) further alters activity and selectivity allowing the activity to be modulated via a self-assembly process. The activity is attributed to the ability to either bind or hydrolyse phosphate esters and mechanistic studies show differential and selective inhibition of multiple kinases by both [L2Cu3]6+ and [L2Zn3]6+ complexes but via different mechanisms.

Does falls-efficacy predict balance performance in older adults with hip osteoarthritis?

This cross-sectional study evaluated the relationship of falls-efficacy to physical performance of functional balance tasks in older adults with hip osteoarthritis (OA). Older adults with hip OA experience several factors associated with fall risk: loss of movement, loss of strength, and increased fear of falls. Seventy-nine men and women age 65 or older were measured for balance, dual task function, and falls-efficacy. Using hierarchical regression, falls-efficacy was a significant predictor of balance when number of medications, age, use of a walking aid, health status, and physical activity level were controlled for. Understanding the role of falls-efficacy in predicting fall risk helps clinicians develop falls screening and prevention programs.

A ligand strand that displays anion-dependant reactivity with acetonitrile; formation of either a mononuclear complex or head-to-tail circular helicate.

The ligand L2,2 contains two bidentate domains separated by a 3,3-diamino-2,2'-biphenyl spacer unit and with Cu(ClO4)2 a mononuclear species is formed (e.g. [Cu(L2,2)]2+). Upon coordination with Cu(triflate)2 the ligand undergoes reaction with an acetonitrile solvent, producing a different ligand with unsymmetrical bidentate and tridentate domains (L2,3). This new ligand results in the formation of a tetranuclear head-to-tail circular helicate [Cu4(L2,3)4]8+ showing that in the presence of the triflate anion the ligand denticity is changed.

The influence of physical activity on lean mass accrual during adolescence: a longitudinal analysis.

During childhood, physical activity is likely the most important modifiable factor for the development of lean mass. However, the effects of normal growth and maturation must be controlled. To distinguish effects of physical activity from normal growth, longitudinal data are required. One hundred nine boys and one hundred thirteen girls, participating in the Saskatchewan Pediatric Bone Mineral Accrual Study, were repeatedly assessed for 6 yr. Age at entry was 8-15 yr. Stature, body mass, and physical activity were assessed biannually. Body composition was assessed annually by dual-energy X-ray absorptiometry. Physical activity was determined using the physical activity questionnaires for children and adolescence. Biological age was defined as years from age of peak height velocity. Data were analyzed using multilevel random-effects models. In boys, it was found that physical activity had a significant time-dependent effect on lean mass accrual of the total body (484.7+/-157.1 g), arms (69.6+/-27.2 g), legs (197.7+/-60.5 g), and trunk (249.1+/-91.4 g) (P<0.05). Although the physical activity effects were similar in the girls (total body: 306.9+/-96.6 g, arms: 31.4+/-15.5 g, legs: 162.9+/-40.0 g, and trunk: 119.6+/-58.2 g; P<0.05), boys for the same level of activity accrued, depending on the site, between 21 and 120% more absolute lean mass (g). In conclusion, habitual physical activity had a significant independent influence on the growth of lean body mass during adolescence, once biological maturity and stature were controlled.

Dihydrogen phosphate-containing dinuclear double assemblies that demonstrate phosphate reactivity to the tetrafluoroborate anion.

The ligands L1 and L2 both form dinuclear assemblies with Cu(ii) and these react with dihydrogen phosphate so that the anion is incorporated within the assembly (e.g. [Cu2L2(H2PO4)]3+). However, in the presence of tetrafluoroborate anions the phosphate undergoes reaction with the anion forming [Cu3(L1)3(O3POBF3)]3+ and [Cu2(L2)2(O2P(OBF3)2)]+.

The history of falls and the association of the timed up and go test to falls and near-falls in older adults with hip osteoarthritis.

BACKGROUND: Falling accounts for a significant number of hospital and long-term care admissions in older adults. Many adults with the combination of advancing age and functional decline associated with lower extremity osteoarthritis (OA), are at an even greater risk. The purpose of this study was to describe fall and near-fall history, location, circumstances and injuries from falls in a community-dwelling population of adults over aged 65 with hip OA and to determine the ability of the timed up and go test (TUG) to classify fallers and near-fallers. METHOD: A retrospective observational study of 106 older men and women with hip pain for six months or longer, meeting a clinical criteria for the presence of hip OA at one or both hips. An interview for fall and near-fall history and administration of the TUG were administered on one occasion. RESULTS: Forty-five percent of the sample had at least one fall in the past year, seventy-seven percent reported occasional or frequent near-falls. The majority of falls occurred during ambulation and ascending or descending steps. Forty percent experienced an injury from the fall. The TUG was not associated with history of falls, but was associated with near-falls. Higher TUG scores occurred for those who were older, less mobile, and with greater number of co-morbidities. CONCLUSION: A high percentage of older adults with hip OA experience falls and near-falls which may be attributed to gait impairments related to hip OA. The TUG could be a useful screening instrument to predict those who have frequent near-falls, and thus might be useful in predicting risk of future falls in this population.

Size-corrected BMD decreases during peak linear growth: implications for fracture incidence during adolescence.

UNLABELLED: Peak adolescent fracture incidence at the distal end of the radius coincides with a decline in size-corrected BMD in both boys and girls. Peak gains in bone area preceded peak gains in BMC in a longitudinal sample of boys and girls, supporting the theory that the dissociation between skeletal expansion and skeletal mineralization results in a period of relative bone weakness. INTRODUCTION: The high incidence of fracture in adolescence may be related to a period of relative skeletal fragility resulting from dissociation between bone expansion and bone mineralization during the growing years. The aim of this study was to examine the relationship between changes in size-corrected BMD (BMDsc) and peak distal radius fracture incidence in boys and girls. MATERIALS AND METHODS: Subjects were 41 boys and 46 girls measured annually (DXA; Hologic 2000) over the adolescent growth period and again in young adulthood. Ages of peak height velocity (PHV), peak BMC velocity (PBMCV), and peak bone area (BA) velocity (PBAV) were determined for each child. To control for maturational differences, subjects were aligned on PHV. BMDsc was calculated by first regressing the natural logarithms of BMC and BA. The power coefficient (pc) values from this analysis were used as follows: BMDsc = BMC/BA(pc). RESULTS: BMDsc decreased significantly before the age of PHV and then increased until 4 years after PHV. The peak rates in radial fractures (reported from previous work) in both boys and girls coincided with the age of negative velocity in BMDsc; the age of peak BA velocity (PBAV) preceded the age of peak BMC velocity (PBMCV) by 0.5 years in both boys and girls. CONCLUSIONS: There is a clear dissociation between PBMCV and PBAV in boys and girls. BMDsc declines before age of PHV before rebounding after PHV. The timing of these events coincides directly with reported fracture rates of the distal end of the radius. Thus, the results support the theory that there is a period of relative skeletal weakness during the adolescent growth period caused, in part, by a draw on cortical bone to meet the mineral demands of the expanding skeleton resulting in a temporary increased fracture risk.

Relationships of activity and sugar drink intake on fat mass development in youths.

PURPOSE: To determine whether a significant relationship exists between fat mass (FM) development and physical activity (PA) and/or sugar-sweetened drink (SD) consumption in healthy boys and girls aged 8-19 yr. METHODS: A total of 105 males and 103 females were assessed during childhood and adolescence for a maximum of 7 yr and a median of 5 yr. Height was measured biannually. Fat-free mass (FFM) and FM were assessed annually by dual x-ray absorptiometry (DXA). PA was evaluated two to three times annually using the PAQ-C/A. Energy intake and SD were assessed using a 24-h dietary intake questionnaire also completed two to three times per year. Years from peak height velocity were used as a biological maturity age indicator. Multilevel random effects models were used to test the relationship. RESULTS: When controlling for maturation, FFM, and energy intake adjusted for SD, PA level was negatively related to FM development in males (P<0.05) but not in females (P>0.05). In contrast, there was no relationship between SD and FM development of males or females (P>0.05). There was also no interaction effect between SD and PA (P>0.05) with FM development. CONCLUSION: This finding lends support to the idea that increasing PA in male youths aids in the control of FM development. Models employed showed no relationship between SD and FM in either gender.

Positive effects of vegetable and fruit consumption and calcium intake on bone mineral accrual in boys during growth from childhood to adolescence: the University of Saskatchewan Pediatric Bone Mineral Accrual Study.

BACKGROUND: Nutrition is an important modifiable factor in the development of bone mass during adolescence. Recent studies of children and adolescents examined the effects of foods such as milk products and fruit and vegetables on bone growth; however, few studies included both boys and girls. OBJECTIVE: The purpose was to ascertain the role of consumption of milk products and vegetables and fruit in the accrual of total-body bone mineral content (TBBMC) in boys and girls from childhood to late adolescence. DESIGN: Seven-year longitudinal data were obtained from 85 boys and 67 girls aged 8-20 y. Biological maturity was defined by the number of years from the age at peak height velocity. Dietary intake was assessed by serial 24-h recalls. Anthropometric measurements and physical activity were assessed every 6 mo. TBBMC assessed with dual-energy X-ray absorptiometry in the fall of each year was the indicator of bone mass. RESULTS: Most boys (87.8%) met Canadian recommendations for milk product intake. Few subjects (<30%) consumed vegetables and fruit in recommended amounts. Using a multilevel modeling statistical approach containing important biological and environmental factors, we found that vegetable and fruit intakes, calcium intake, and physical activity were significant independent environmental predictors of TBBMC in boys but not in girls. CONCLUSIONS: In addition to adequate dietary calcium intake, appropriate intakes of vegetables and fruit have a beneficial effect on TBBMC in boys aged 8-20 y. Underreporting of dietary intake by girls may explain why this effect was not apparent in girls.

Strength indices of the proximal femur and shaft in prepubertal female gymnasts.

INTRODUCTION/PURPOSE: The role of impact loading activity on bone mass is well established; however, there are little data on the effects of exercise on bone geometry and indices of bone strength. The primary purpose of this study was to compare indices of bone strength at the proximal femur (PF) between elite premenarcheal gymnasts (N= 30) and age-matched controls (N= 30). METHODS: Structural properties of the proximal femur were derived from the hip analyses program and included measurement of subperiosteal width, endosteal diameter, cross-sectional area, bone mineral density, cross-section moment of inertia (CSMI), and section modulus (Z). These parameters were measured for two regions of the PF: the narrow neck (NN), and the shaft (S). In addition, a strength index (S-SI) was calculated at the shaft by dividing the Z at the shaft by the femur length. A secondary purpose was to compare bone mineral content (BMC) values at the total body, lumbar spine, and three sites at the PF (neck, trochanter, and total) between the groups. All dependent values were compared adjusting for height and weight using an ANCOVA procedure and for relative lean body mass. RESULTS The gymnasts had significantly greater size-adjusted strength indices (CSMI, Z, and SI) at the NN and S. Gymnasts also had significantly greater size-adjusted BMC at all sites investigated. However, these differences disappeared when adjusted for relative lean body mass. CONCLUSION: When adjusted for body size, gymnasts had significantly greater indices of both axial strength and bending strength at the NN region of the PF and S, as well as a greater bone SI at the femoral shaft. These differences may be related to greater relative lean body mass attained in gymnastics training.

Effect of physical activity on bone mineral density assessed by limb dominance across the lifespan.

Bone mineral density is higher in dominant vs. nondominant limbs, implying that the greater use of dominant limbs in everyday activities results in the deposition of more bone or that the dominant limb is genetically larger. The objective of the present study was to determine whether bone mineral density differences between dominant and nondominant arms were greater in older vs. younger women. To determine whether this was due to a greater lifetime of preferential loading of the dominant arm, differences between dominant and nondominant arms were compared to accumulated amounts of physical activities which emphasized use of the dominant arm. Bone mineral density of dominant and nondominant arms was assessed by dual-energy X-ray absorptiometry in groups of younger (n = 35; age = 20.9) and older (n = 53; age = 57.4) women. The difference between arms was greater in the older vs. the younger group (5.2% vs. 1.9%, respectively, P < 0.01). Within the older group, total lifetime energy expenditure during activities emphasizing loading of the dominant arm correlated with the bone mineral difference between dominant and nondominant arms (r = 0.47, P < 0.01). This implies that a greater lifetime of preferential loading of the dominant arm in the older group resulted in a greater difference between arms. Am. J. Hum. Biol. 12:633-637, 2000. Copyright 2000 Wiley-Liss, Inc.

Higher premenarcheal bone mass in elite gymnasts is maintained into young adulthood after long-term retirement from sport: a 14-year follow-up.

Sports that impact-load the skeleton during childhood and adolescence increase determinants of bone strength such as bone mineral content and density; however, it is unclear if this benefit is maintained after retirement from the sport. The purpose of this study was to assess whether the previously reported higher bone mass in a group of premenarcheal gymnasts was still apparent 10 years after the cessation of participation and withdrawal of the gymnastics loading stimulus. In 1995, 30 gymnasts 8 to 15 years of age were measured and compared with 30 age-matched nongymnasts. Twenty-five former gymnasts and 22 nongymnasts were measured again 14 years later (2009 to 2010). Gymnasts had been retired from gymnastics training and competition for an average of 10 years. Total body (TB), lumbar spine (LS), and femoral neck (FN) bone mineral content (BMC) was assessed at both measurement occasions by dual-energy X-ray absorptiometry (DXA). Multivariate analysis of covariance (MANCOVA) was used to compare former gymnasts' and nongymnasts' BMC while controlling for differences in body size and maturation (covariates: age, height, weight, and years from menarche [1995] or age at menarche [2009 to 2010]). Premenarcheal gymnasts (measured in 1995) had significantly greater size-adjusted TB, LS, and FN BMC (p < 0.05) (15%, 17%, and 12%, respectively) than nongymnasts. Ten years after retirement, gymnasts had maintained similar size-adjusted TB, LS, and FN BMC differences (p < 0.05) (13%, 19%, and 13%, respectively) when compared with nongymnasts. Bone mass benefits in premenarcheal gymnasts were still apparent even after long-term (10 years) removal of the gymnastics loading stimulus.

Former premenarcheal gymnasts exhibit site-specific skeletal benefits in adulthood after long-term retirement.

Young female gymnasts have greater bone strength compared to controls; although possibly due to selection into gymnastics, it is thought that their loading activity during growth increases their bone mass, influencing both bone geometry and architecture. If such bone mass and geometric adaptations are maintained, this may potentially decrease the risk of osteoporosis and risk of fracture later in life. However, there is limited evidence of the persisting benefit of gymnastic exercise during growth on adult bone geometric parameters. Therefore, the purpose of this study was to determine whether adult bone geometry, volumetric density, and estimated strength were greater in retired gymnasts compared to controls, 10 years after retirement from the sport. Bone geometric and densitometric parameters, measured by peripheral quantitative computed tomography (pQCT) at the radius and tibia, were compared between 25 retired female gymnasts and 22 controls, age range 22 to 30 years, by multivariate analysis of covariance (covariates: age, height, and muscle cross-sectional area). Retired gymnasts had significantly greater adjusted total and trabecular area (16%), total and trabecular bone mineral content (BMC) (18% and 22%, respectively), and estimated strength (21%) at the distal radius (p < 0.05) than controls. Adjusted total and cortical area and BMC, medullary area, and estimated strength were also significantly greater (13% to 46%) in retired gymnasts at the 30% and 65% radial shaft sites (p < 0.05). At the distal tibia, retired gymnasts had 12% to 13% greater total and trabecular BMC and volumetric bone mineral density as well as 21% greater estimated strength; total and cortical BMC and estimated strength were also greater at the tibial shaft (8%, 11%, and 10%, respectively) (p < 0.05). Former female gymnasts have significantly better geometric and densitometric properties, as well as estimated strength, at the radius and tibia 10 years after retirement from gymnastics compared to females who did not participate in gymnastics in childhood and adolescence.