Urine antimony and risk of cardiovascular disease - A prospective case-cohort study in Danish Non-Smokers.

BACKGROUND: Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. OBJECTIVES: To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. METHODS: Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50-64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. RESULTS: In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. DISCUSSION: Among this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.

Urinary Cadmium and Incident Heart Failure: A Case-Cohort Analysis Among Never-Smokers in Denmark.

BACKGROUND: Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked. METHODS: Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale. RESULTS: Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 µg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR = 1.1 per interquartile range difference [95% CI = 1.0, 1.2). In sex-stratified analyses, the association seemed restricted to men (aHR = 1.5 [95% CI = 1.2, 1.9]). CONCLUSIONS: In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men.

Relationship between Urine Creatinine and Urine Osmolality in Spot Samples among Men and Women in the Danish Diet Cancer and Health Cohort.

Assays of urine biomarkers often use urine creatinine to account for urinary dilution, even though creatinine levels are influenced by underlying physiology and muscle catabolism. Urine osmolality-a measure of dissolved particles including ions, glucose, and urea-is thought to provide a more robust marker of urinary dilution but is seldom measured. The relationship between urine osmolality and creatinine is not well understood. We calculated correlation coefficients between urine creatinine and osmolality among 1375 members of a subcohort of the Danish Diet, Cancer, and Health Cohort, and within different subgroups. We used linear regression to relate creatinine with osmolality, and a lasso selection procedure to identify other variables that explain remaining variability in osmolality. Spearman correlation between urine creatinine and osmolality was strong overall (ρ = 0.90; 95% CI: 0.89-0.91) and in most subgroups. Linear regression showed that urine creatinine explained 60% of the variability in urine osmolality, with another 9% explained by urine thallium (Tl), cesium (Cs), and strontium (Sr). Urinary creatinine and osmolality are strongly correlated, although urine Tl, Cs, and Sr might help supplement urine creatinine for purposes of urine dilution adjustment when osmolality is not available.

Urine cadmium and acute myocardial infarction among never smokers in the Danish Diet, Cancer and Health cohort.

Cadmium exposure has been associated with cardiovascular disease. Cigarette smoking is a key source of cadmium exposure and thus a potential confounder in observational studies of environmental cadmium and cardiovascular disease that include tobacco smokers. We leveraged up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to test the hypothesis that cadmium exposure is associated with acute myocardial infarction (AMI) among people who never smoked. Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) were enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 males and 600 females. We identified 809 AMI cases occurring between baseline and the end of 2015 using the Danish National Patient Registry. We quantified cadmium, creatinine, and osmolality in baseline urine samples. Using an unweighted case-cohort approach, we estimated adjusted hazard ratios (aHR) for AMI in Cox proportional hazards models with age as the time axis. Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 µg cadmium/g creatinine). We did not find strong evidence to support an association between higher urinary cadmium and AMI when comparing the highest versus lowest quartile (aHR = 1.16; 95% CI: 0.86 - 1.56) and per IQR increment in cadmium concentration (aHR = 1.02; 95% CI: 0.93 - 1.12). Results were not materially different across strata defined by sex. Results were generally similar using creatinine or osmolality to account for differences in urine dilution. While cadmium exposure has been identified as a risk factor for cardiovascular disease, we did not find strong evidence that urinary cadmium at relatively low-levels is associated with AMI among people who have never smoked.

Serum trace metal association with response to erythropoiesis stimulating agents in incident and prevalent hemodialysis patients.

Alterations in hemodialysis patients' serum trace metals have been documented. Early studies addressing associations levels of serum trace metals with erythropoietic responses and/or hematocrit generated mixed results. These studies were conducted prior to current approaches for erythropoiesis stimulating agent (ESA) drug dosing guidelines or without consideration of inflammation markers (e.g. hepcidin) important for regulation of iron availability. This study sought to determine if the serum trace metal concentrations of incident or chronic hemodialysis patients associated with the observed ESA response variability and with consideration to ESA dose response, hepcidin, and high sensitivity C-reactive protein levels. Inductively-coupled plasma-mass spectrometry was used to measure 14 serum trace metals in 29 incident and 79 prevalent dialysis patients recruited prospectively. We compared these data to three measures of ESA dose response, sex, and dialysis incidence versus dialysis prevalence. Hemoglobin was negatively associated with ESA dose and cadmium while positively associated with antimony, arsenic and lead. ESA dose was negatively associated with achieved hemoglobin and vanadium while positively associated with arsenic. ESA response was positively associated with arsenic. Vanadium, nickel, cadmium, and tin were increased in prevalent patients. Manganese was increased in incident patients. Vanadium, nickel, and arsenic increased with time on dialysis while manganese decreased. Changes in vanadium and manganese were largest and appeared to have some effect on anemia. Incident and prevalent patients' chromium and antimony levels exceeded established accepted upper limits of normal.

The kinetics of dimethylhydroxypyridinone interactions with iron(iii) and the catalysis of iron(iii) ligand exchange reactions: implications for bacterial iron transport and combination chelation therapies.

Many microbes acquire environmental Fe by secreting organic chelators, siderophores, which possess the characteristics of a high and specific binding affinity for iron(iii) that results in the formation of thermodynamically stable, and kinetically inert iron(iii) complexes. Mechanisms to overcome the kinetic inertness include the labilization of iron(iii) by means of ternary complex formation with small chelators. This study describes a kinetic investigation of the labilization of iron(iii) between two stable binding sites, the prototypical siderophore ferrioxamine B and EDTA, by the bidentate siderophore mimic, 1,2-dimethyl-3-hydroxy-4-pyridinone (L1, H(DMHP)). The proposed mechanism is substantiated by investigating the iron(iii) exchange reaction between ferrioxamine B and H(DMHP) to form Fe(DMHP)3, as well as the iron(iii) exchange from Fe(DMHP)3 to EDTA. It is also shown that H(DMHP) is a more effective catalyst for the iron(iii) exchange reaction than bidentate hydroxamate chelators reported previously, supporting the hypothesis that chelator structure and iron(iii) affinity influence low denticity ligand facilitated catalysis of iron(iii) exchange reactions. The results are also discussed in the context of the design and use of combination chelator therapies in the treatment of Fe overload in humans.

Low levels of lead and glutathione markers of redox status in human blood.

Exposure to lead (Pb) is implicated in a plethora of health threats in both adults and children. Increased exposure levels are associated with oxidative stress in the blood of workers exposed at occupational levels. However, it is not known whether lower Pb exposure levels are related to a shift toward a more oxidized state. To assess the association between blood lead level (BLL) and glutathione (GSH) redox biomarkers in a population of healthy adults, BLL and four GSH markers (GSH, GSSG, GSH/GSSG ratio and redox potential E h ) were measured in the blood of a cross-sectional cohort of 282 avid seafood-eating healthy adults living on Long Island (NY). Additionally, blood levels of two other metals known to affect GSH redox status, selenium (Se) and mercury (Hg), and omega-3 index were tested for effect modification. Regression models were further adjusted for demographic and smoking status. Increasing exposure to Pb, measured in blood, was not associated with GSSG, but was associated with lower levels of GSH/GSSG ratio and more positive GSH redox potential E h , driven by its association with GSH. No effect modification was observed in analyses stratified by Hg, Se, omega-3 index, sex, age, or smoking. Blood Pb is associated with lower levels of GSH and the GSH/GSSG ratio in this cross-sectional study of healthy adults.

Temporal variability of urinary cadmium in spot urine samples and first morning voids.

Cadmium is a carcinogenic heavy metal. Urinary levels of cadmium are considered to be an indicator of long-term body burden, as cadmium accumulates in the kidneys and has a half-life of at least 10 years. However, the temporal stability of the biomarker in urine samples from a non-occupationally exposed population has not been rigorously established. We used repeated measurements of urinary cadmium (U-Cd) in spot urine samples and first morning voids from two separate cohorts, to assess the temporal stability of the samples. Urine samples from two cohorts including individuals of both sexes were measured for cadmium and creatinine. The first cohort (Home Observation of Perinatal Exposure (HOPE)) consisted of 21 never-smokers, who provided four first morning urine samples 2-5 days apart, and one additional sample roughly 1 month later. The second cohort (World Trade Center-Health Program (WTC-HP)) consisted of 78 individuals, including 52 never-smokers, 22 former smokers and 4 current smokers, who provided 2 spot urine samples 6 months apart, on average. Intra-class correlation was computed for groups of replicates from each individual to assess temporal variability. The median creatinine-adjusted U-Cd level (0.19 and 0.21 µg/g in the HOPE and WTC-HP, respectively) was similar to levels recorded in the United States by the National Health and Nutrition Examination Survey. The intra-class correlation (ICC) was high (0.76 and 0.78 for HOPE and WTC-HP, respectively) and similar between cohorts, irrespective of whether samples were collected days or months apart. Both single spot or first morning urine cadmium samples show good to excellent reproducibility in low-exposure populations.

Characterization of Zinc Carbonate Basic as a Source of Zinc in a Rodent Study Investigating the Effects of Dietary Deficiency or Excess.

Zinc deficiency and excess can result in adverse health outcomes. There is conflicting evidence regarding whether excess or deficient zinc in the diet can contribute to carcinogenicity. The objective of this study was to characterize zinc carbonate basic for use as a source of dietary zinc in a rodent toxicity and carcinogenicity study investigating the effects of zinc deficiency and excess. Because of the complex chemistries of zinc carbonate basic compounds, inconsistent nomenclature, and literature and reference spectra gaps, it was necessary to employ multiple analytical techniques, including Karl Fischer titration, combustion analysis, inductively coupled plasma-optical emission spectrometry, X-ray diffraction, infrared spectroscopy, X-ray fluorescence spectrometry, and thermogravimetric analysis to characterize the test article. Based on the collective evidence and through the process of elimination, the test article was found to be composed mainly of zinc carbonate basic with zinc oxide as a minor component. The zinc content was determined to be 56.6% (w/w) with heavy metals such as arsenic, cadmium, mercury and lead below the limit of quantitation of less than or equal to 0.01%. The test material was stable at ambient temperature. Based on the work described in this manuscript, the test article was suitable for use as a source of zinc in studies of deficiency and excess in the diet.

Urinary Cadmium and Breast Cancer: A Prospective Danish Cohort Study.

Background: Cadmium is a human lung carcinogen, and recent evidence suggests it may play a role in hormone-related cancers because of its estrogenic activity. Case-control studies consistently show higher cadmium concentrations in urine from women diagnosed with breast cancer compared with control women. Our aim was to investigate the association between urinary cadmium and breast cancer in a prospective design. Methods: We conducted a case-cohort study using the population-based Danish Diet Cancer and Health Cohort. Women age 50 to 64 years were recruited in 1993-1997 and provided urine for analysis. We identified 900 incident case patients in the Danish Cancer Registry and compared with 898 individuals in a subcohort. Urine samples collected at enrollment into the cohort were analyzed for cadmium and creatinine. We estimated incidence rate ratios (IRRs) for breast cancer in Cox proportional hazards models with age as time axis and calculated 95% confidence intervals (CIs). Results: The linear analysis showed no association between urinary cadmium and risk for breast cancer (IRR = 1.00, 95% CI = 0.81 to 1.24 per ng Cd/mL urine). The categorical analyses showed a slightly higher risk for breast cancer for the second (IRR = 1.10, 95% CI = 0.86 to 1.42) and third (IRR = 1.14, 95% CI = 0.83 to 1.55) exposure tertiles compared with the lowest tertile. Results were similar in analyses of breast cancer subtypes defined by estrogen and progesterone receptor status and by histology, and analyses stratified by years from baseline to diagnosis. Conclusions: This large prospective study showed no association between urinary concentration of cadmium and subsequent risk for development of postmenopausal breast cancer.

Dietary Intake Estimates and Urinary Cadmium Levels in Danish Postmenopausal Women.

BACKGROUND: Cadmium is a known carcinogen that can disrupt endocrine signalling. Cigarette smoking and food are the most common routes of non-occupational exposure to cadmium. Cadmium accumulates in the kidney and can be measured in urine, making urine cadmium (U-Cd) a biomarker of long-term exposure. However dietary-cadmium (D-Cd) intake estimates are often used as surrogate indicator of cadmium exposure in non-smoking subjects. It is therefore important to investigate the concordance between D-Cd estimates obtained with Food Frequency Questionnaires and U-Cd. METHODS: U-Cd levels were compared with estimated dietary-cadmium (D-Cd) intake in 1764 post-menopausal women from the Danish Diet, Cancer and Health cohort. For each participant, a food frequency questionnaire, and measures of cadmium content in standard recipes were used to judge the daily intake of cadmium, normalized by daily caloric intake. Cadmium was measured by ICP-MS in spot urine sampled at baseline and normalized by urinary creatinine. Information on diet, socio-demographics and smoking were self-reported at baseline. RESULTS: Linear regressions between U-Cd and D-Cd alone revealed minimal but significant positive correlation in never smokers (R2 = 0.0076, ß = 1.5% increase per 1 ng Cd kcal(-1), p = 0.0085, n = 782), and negative correlation in current smokers (R2 = 0.0184, ß = 7.1% decrease per 1 ng Cd kcal(-1) change, p = 0.0006, n = 584). In the full study population, most of the variability in U-Cd was explained by smoking status (R2 = 0.2450, n = 1764). A forward selection model revealed that the strongest predictors of U-Cd were age in never smokers (Δ R2 = 0.04), smoking duration in former smokers (Δ R2 = 0.06) and pack-years in current smokers (Δ R2 = 0.07). Food items that contributed to U-Cd were leafy vegetables and soy-based products, but explained very little of the variance in U-Cd. CONCLUSIONS: Dietary-Cd intake estimated from food frequency questionnaires correlates only minimally with U-Cd biomarker, and its use as a Cd exposure indicator may be of limited utility in epidemiologic studies.

Characterization of the aqueous iron(III) chelation chemistry of a potential Trojan Horse antimicrobial agent: chelate structure, stability and pH dependent speciation.

The aqueous solution equilibria of a ß-lactam antimicrobial agent containing a 3-hydroxy, 4-pyridinone group (L (PF)) binding to Fe(III) in aqueous solution has been characterized through spectrophotometric and potentiometric titrations. The metal-free ligand has four observable protonation constants, pK(a1) = 2.6, pK(a2) = 3.43, pK(a3) = 6.43, and pK(a4) = 9.62. L (PF) forms a 3:1 ligand:Fe(III) complex in aqueous solution through coordinate-covalent bond formation exclusively involving the bidentate hydroxypyridinone moiety. This 3:1 L (PF):Fe complex was found to have a stability constant of log ß(130) = 33.46. A speciation diagram for the L (PF) system demonstrates that in the region of physiological pH the tris-(L (PF))Fe(III) complex, Fe(L(PF)) (3) (6-) , predominates. This complex exhibits two irreversible reduction waves in solution at -30 mV versus NHE, corresponding to a ligand-based reduction, and at -385 mV versus NHE, corresponding to an irreversible Fe(3+)/Fe(2+) reduction of the Fe(L(PF)) (3) (6-) complex.

Amelioration of metal-induced toxicity in Caenorhabditis elegans: utility of chelating agents in the bioremediation of metals.

The presence of toxic amounts of transition metals in the environment may originate from a range of human activities and natural processes. One method for the removal of toxic levels of metals is through chelation by small molecules. However, chelation is not synonymous with detoxification and may not affect the bioavailability of the metal. To test the bioavailability of chelated metals in vivo, the effects of several metal/chelator combinations were tested in the environmentally relevant organism Caenorhabditis elegans. The effect of metal exposure on nematode growth was used to determine the toxicity of cadmium, copper, nickel, and zinc. The restoration of growth to levels observed in nonexposed nematodes was used to determine the protective effects of the polydentate chelators: acetohydroxamic acid (AHA), cyclam, cysteine, calcium EDTA, desferrioxamine B, 1,2-dimethyl,3-hydroxy,4-pyridinone, and histidine. Cadmium toxicity was removed only by EDTA; copper toxicity was removed by all of the chelators except AHA; nickel toxicity was removed by cyclam, EDTA, and histidine; and zinc toxicity was removed by only EDTA. These results demonstrate the utility of polydentate chelators in the remediation of metal-contaminated systems. They also demonstrate that although the application of a chelator to metal contaminants may be effective, binding alone cannot be used to predict the level of remediation. Remediation depends on a number of factors, including metal complex speciation in the environment.

Characterization of Fe(III) sequestration by an analog of the cytotoxic siderophore brasilibactin A: implications for the iron transport mechanism in mycobacteria.

Mycobacteria such as M. tuberculosis represent a significant health concern throughout much of the developing world. In mycobacteria and other pathogenic bacteria, an important virulence factor is the ability of the bacterium to obtain iron from its host. One means of obtaining iron is through the use of siderophores. Brasilibactin A is a membrane bound siderophore produced by Nocardia brasiliensis with structural similarity to the mycobactin class of siderophore in mycobacteria. A characterization of the protonation constants and Fe(III) affinity of a water soluble Brasilibactin A analog (Bbtan) has been performed. Using protonation constants and competition with EDTA, the stability constant of the 1 : 1 Fe(III)-Bbtan complex was found to be log ß(110) = 26.96. The pFe of Bbtan is 22.73, somewhat low for a proposed siderophore molecule. The redox potential of the Fe-Bbtan complex was found to be -300 mV vs. NHE, very high for an iron-siderophore complex. The combination of relatively low complex stability and ease of iron reduction may play a crucial role in the mechanism of mycobactin siderophore-mediated iron uptake in mycobacteria and related organisms.

Synthesis and iron sequestration equilibria of novel exocyclic 3-hydroxy-2-pyridinone donor group siderophore mimics.

The synthesis of a novel class of exocyclic bis- and tris-3,2-hydroxypyridinone (HOPO) chelators built on N(2) and N(3) aza-macrocyclic scaffolds and the thermodynamic solution characterization of their complexes with Fe(III) are described. The chelators for this study were prepared by reaction of either piperazine or N,N',N''-1,4,7-triazacyclononane with a novel electrophilic HOPO iminium salt in good yields. Subsequent removal of the benzyl protecting groups using HBr/acetic acid gave bis-HOPO chelators N(2)(etLH)(2) and N(2)(prLH)(2), and tris-HOPO chelator N(3)(etLH)(3) in excellent yields. Solution thermodynamic characterization of their complexes with Fe(III) was accomplished using spectrophotometric, potentiometric, and electrospray ionization-mass spectrometry (ESI-MS) methods. The pK(a)'s of N(2)(etLH)(2), N(2)(prLH)(2), and N(3)(etLH)(3), were determined spectrophotometrically and potentiometrically. The Fe(III) complex stability constants for the tetradentate N(2)(etLH)(2) and N(2)(prLH)(2), and hexadentate N(3)(etLH)(3), were measured by spectrophotometric and potentiometric titration, and by competition with ethylenediaminetetraacetic acid (EDTA). N(3)(etLH)(3) forms a 1:1 complex with Fe(III) with log ß(110) = 27.34 ± 0.04. N(2)(prLH)(2) forms a 3:2 L:Fe complex with Fe(III) where log ß(230) = 60.46 ± 0.04 and log ß(110) = 20.39 ± 0.02. While N(2)(etLH)(2) also forms a 3:2 L:Fe complex with Fe(III), solubility problems precluded determining log ß(230); log ß(110) was found to be 20.45 ± 0.04. The pFe values of 26.5 for N(3)(etLH)(3) and 24.78 for N(2)(prLH)(2) are comparable to other siderophore molecules used in the treatment of iron overload, suggesting that these hydroxypyridinone ligands may be useful in the development of new chelation therapy agents.

The redox hypothesis in siderophore-mediated iron uptake.

The viability of iron(III/II) reduction as the initial step in the in vivo release of iron from its thermodynamically stable siderophore complex is explored.

Iron chelation equilibria, redox, and siderophore activity of a saccharide platform ferrichrome analogue.

A complete characterization of the aqueous solution Fe(III) and Fe(II) coordination chemistry of a saccharide-based ferrichrome analogue, 1-O-methyl-2,3,6-tris-O-[4-(N-hydroxy-N-ethylcarbamoyl)-n-butyryl]-alpha-D-glucopyranoside (H3LN236), is reported including relevant thermodynamic parameters and growth promotion activity with respect to both Gram-negative and Gram-positive bacterial strains. The saccharide platform is an attractive backbone for the design and synthesis of ferrichrome analogues because of its improved water solubility and hydrogen-bonding capabilities, which can potentially provide favorable receptor recognition and biological activity. The ligand deprotonation constants (pKa values), iron complex (FeIII(LN236) and FeII(LN236)1-) protonation constants (KFeHxL-236-N), overall Fe(III) and Fe(II) chelation constants (beta110), and aqueous solution speciation were determined by spectrophotometric and potentiometric titrations, EDTA competition equilibria, and cyclic voltammetry. Log betaIII110 = 31.16 and pFe = 26.1 for FeIII(LN236) suggests a high affinity for Fe(III), which is comparable to or greater than ferrichrome and other ferrichrome analogues. The E1/2 for the FeIII(LN236)/FeII(LN236)1- couple was determined to be -454 mV (vs NHE) from quasi-reversible cyclic voltammograms at pH 9. Below pH 6.5, the E1/2 shifts to more positive values and the pH-dependent E1/2 profile was used to determine the FeII(LN236)1- protonation constants and overall stability constant log betaII110 = 11.1. A comparative analysis of similar data for an Fe(III) complex of a structural isomer of this exocyclic saccharide chelator (H3LR234), including strain energy calculations, allows us to analyze the relative effects of the pendant arm position and hydroxamate moiety orientation (normal vs retro) on overall complex stability. A correlation between siderophore activity and iron coordination chemistry of these saccharide-hydroxamate chelators is made.

Possible role of relativistic effects in the plasticity of the coordination geometry of cadmium(II). A voltammetric study of the stability of the complexes of cadmium(II) with 12-crown-4,15-crown-5 and 18-crown-6 in aqueous solution and the structures of [Cd(benzo-18-crown-6)(NCS)(2)] and [K(18-crown-6)][Cd(SCN)(3)].

A differential pulse voltammetric study of complexes of Cd(II) and Pb(II) with crown ethers is reported. Measured log K(1) values for Cd(II) with 18-crown-6 (1,4,7,10,13,16-hexaoxacyclooctadecane), 15-crown-5 (1,4,7,10,13-pentaoxacyclopentadecane), and 12-crown-4 (1,4,7,10-tetraoxacyclododecane) are respectively 2.53 (+/-0.06), 1.97 (+/-0.07), and 1.72 (+/-0.08) and for Pb(II) with 18-crown-6 is 4.17 (+/-0.03), all at 25 degrees C in 0.1 M LiNO(3). Cd(II) is smaller than is usually associated with strong bonding with crown ethers. The high log K(1) values for Cd(2+) with crown ethers found here are discussed in terms of distortion of Cd(II) by relativistic effects. The resulting plasticity of the coordination geometry of the Cd(II) ion allows it to meet the metal ion size requirements of all the crown ethers, allowing high log K(1) values to occur. Crystal structures for [Cd(bz-18-crown-6)(SCN)(2)] (1) (bz-18-crown-6 = benzo-1,4,7,10,13,16-hexaoxacyclooctadecane) and [K(18-crown-6)][Cd(SCN)(3)] (2) are reported. 1 was triclinic, space group P1, a = 8.5413(2), b = 10.0389(2), and c = 13.4644(2) A, alpha = 94.424(1), beta = 102.286(1), and gamma = 93.236(1) degrees, Z = 2, and final R = 0.023. 2 was orthorhombic, space group Cmc2(1), a = 14.7309(3), b = 15.1647(3), and c = 10.6154(2) A, Z = 4, and final R = 0.020. In 1, the Cd occupies the cavity of the bz-18-crown-6 with long average Cd-O bond lengths of 2.65 A and is N-bonded to the thiocyanates with short average Cd-N bonds of 2.12 A. In [Cd(bz-18-crown-6)(SCN)(2)], the linear coordination involving the Cd and the two N-bonded thiocyanate groups in 1 is discussed in terms of the role of relativistic effects in the tendency to linear coordination geometry in group 12 metal ions. In 2 Cd forms a polymeric structure involving thiocyanate bridges between Cd atoms and K(+) occupies the cavity of the crown ether. 2 highlights the fact that cadmium is almost never S-bonded to thiocyanate except in bridging thiocyanates.