Organoiridium Complexes Enhance Cellular Defense Against Reactive Aldehydes Species.

Although reactive aldehyde species (RASP) are associated with the pathogenesis of many major diseases, there are currently no clinically approved treatments for RASP overload. Conventional aldehyde detox agents are stoichiometric reactants that get consumed upon reacting with their biological targets, which limits their therapeutic efficiency. To achieve longer-lasting detoxification effects, small-molecule intracellular metal catalysts (SIMCats) were used to protect cells by converting RASP into non-toxic alcohols. It was shown that SIMCats were significantly more effective in lowering cell death from the treatment with 4-hydroxynon-2-enal than aldehyde scavengers over a 72 h period. Studies revealed that SIMCats reduced the aldehyde accumulation in cells exposed to the known RASP inducer arsenic trioxide. This work demonstrates that SIMCats offer unique benefits over stochiometric agents, potentially providing new ways to combat diseases with greater selectivity and efficiency than existing approaches.

Sex differences in quality of life of patients following percutaneous coronary intervention in Vietnam.

PURPOSE: Data regarding the health-related quality of life (HRQoL) in men and women after percutaneous coronary intervention (PCI) in low-and-middle incomes countries remains scarce. To investigate sex difference in the HRQoL at 30 days and 12 months post PCI in Vietnam. METHODS: We used data from a single percutaneous coronary registry established in the Vietnam National Heart Institute. The HRQoL was measured using the EQ-5D-3L instrument via telephone interviews, and information about demographics, clinical presentation and procedures was obtained through face-to-face interviews and medical records. The HRQoL between men and women were compared using independent samples t tests, the Mann-Whitney U test or univariate/multivariate logistic regression. RESULTS: There were 866 patients included in this cohort, with the proportion of women being nearly half of men (32.1 vs 67.9%). Women were 3.5 years older, had lower income and educational levels but greater prevalence of cardiovascular risk factors. At 30 days, women significantly had more problems in mobility, personal care and pain/discomfort compared to men. At 12 months, women had more problem than men in usual activity. The geometric means of HRQoL was lower in women at 30 days, but not in 12 months. From 30 days to 12 months after discharge, women showed better recovery in mobility compared to men, but not in other dimensions. CONCLUSIONS: In this first insight of sex differences in HRQoL following PCI in Vietnam, women appeared to have worse quality of life, especially at 30 days after discharge but they showed better recovery in mobility at 12 months compared to men.

Harmonising Individual Patient Level Cardiac Registry Data Across the Asia Pacific Region-A Feasibility Study of In-Hospital Outcomes of STEMI Patients From the Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) Network.

OBJECTIVE: The Asia-Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration was established to inform on percutaneous coronary intervention (PCI) in the Asia-Pacific Region. Our aims were to (i) determine the operational requirements to assemble an international individual patient dataset and validate the processes of governance, data quality and data security, and subsequently (ii) describe the characteristics and outcomes for ST-elevation myocardial infarction (STEMI) patients undergoing PCI in the ASPECT registry. METHODS: Seven (7) ASPECT members were approached to provide a harmonised anonymised dataset from their local registry. Patient characteristics were summarised and associations between the characteristics and in-hospital outcomes for STEMI patients were analysed. RESULTS: Six (6) participating sites (86%) provided governance approvals for the collation of individual anonymised patient data from 2015 to 2017. Five (5) sites (83%) provided >90% of agreed data elements and 68% of the collated elements had <10% missingness. From the registry (n=12,620), 84% were male. The mean age was 59.2±12.3 years. The Malaysian cohort had a high prevalence of previous myocardial infarction (34%), almost twice that of any other sites (p<0.001). Adverse in-hospital outcomes were the lowest in Hong Kong whilst in-hospital mortality varied from 2.7% in Vietnam to 7.9% in Singapore. CONCLUSIONS: Governance approvals for the collation of individual patient anonymised data was achieved with a high level of data alignment. Secure data transfer process and repository were established. Patient characteristics and presentation varied significantly across the Asia-Pacific region with this likely to be a major predictor of variations in the clinical outcomes observed across the region.

Variations in Intracellular Organometallic Reaction Frequency Captured by Single-Molecule Fluorescence Microscopy.

Studies of organometallic reactions in living cells commonly rely on ensemble-averaged measurements, which can obscure the detection of reaction dynamics or location-specific behavior. This information is necessary to guide the design of bioorthogonal catalysts with improved biocompatibility, activity, and selectivity. By leveraging the high spatial and temporal resolution of single-molecule fluorescence microscopy, we have successfully captured single-molecule events promoted by Ru complexes inside live A549 human lung cells. By observing individual allylcarbamate cleavage reactions in real-time, our results revealed that they occur with greater frequency inside the mitochondria than in the non-mitochondria regions. The estimated turnover frequency of the Ru complexes was at least 3-fold higher in the former than the latter. These results suggest that organelle specificity is a critical factor to consider in intracellular catalyst design, such as in developing metallodrugs for therapeutic applications.

Customizing Polymers by Controlling Cation Switching Dynamics in Non-Living Polymerization.

Controlling the chain growth process in non-living polymerization reactions is difficult because chain termination typically occurs faster than the time it takes to apply an external trigger. To overcome this limitation, we have developed a strategy to regulate non-living polymerizations by exploiting the chemical equilibria between a metal catalyst and secondary metal cations. We have prepared two nickel phenoxyphosphine-polyethylene glycol variants, one with 2-methoxyphenyl (Ni1) and another with 2,6-dimethoxyphenyl (Ni2) phosphine substituents. Ethylene polymerization studies using these complexes in the presence of alkali salts revealed that chain growth is strongly dependent on electronic effects, whereas chain termination is dependent on both steric and electronic effects. By adjusting the solvent polarity, we can favor polymerizations via non-switching or dynamic switching modes. For example, in a 100:0.2 mixture of toluene/diethyl ether, reactions of Ni1 and both Li+ and Na+ cations in the presence of ethylene yielded bimodal polymers with different relative fractions depending on the Li+/Na+ ratio used. In a 98:2 mixture of toluene/diethyl ether, reactions of Ni2 and Cs+ in the presence of ethylene generated monomodal polyethylene with dispersity <2.0 and increasing molecular weight as the amount of Cs+ added increased. Solution studies by NMR spectroscopy showed that cation exchange between the nickel complexes and alkali cations in 98:2 toluene/diethyl ether is fast on the NMR time scale, which supports our proposed dynamic switching mechanism.

Rigidifying Cation-Tunable Nickel Catalysts Increases Activity and Polar Monomer Incorporation in Ethylene and Methyl Acrylate Copolymerization.

In this study, we synthesized and characterized two nickel complexes featuring conformationally rigid bisphosphine mono-oxide ligands, where one has an o-methoxyphenyl (Ni2) and the other has an o-(2-methoxyethoxy)phenyl (Ni3) substituent on the P═O moiety. We performed metal binding studies using Ni3 and found that its reaction with Li+ and Na+ most likely produced 1:1 and 1:1/2:1 nickel:alkali species in solution, respectively. The nickel complexes were competent catalysts for ethylene homopolymerization and copolymerization, with activities up to 3.8 × 103 and 8.1 × 10 kg mol-1 h-1, respectively. In reactions of ethylene with methyl acrylate (1.0 M), the addition of Li+ to Ni3 led to a 5.4-fold enhancement in catalyst activity and a 1.9-fold increase in polar monomer incorporation in comparison to those by Ni3 alone under optimized conditions. A comparison with other nickel catalysts reported for ethylene and methyl acrylate copolymerization revealed that our nickel-alkali catalysts are competitive with some of the most efficient Ni-based systems developed thus far.

Scope and Limitations of Reductive Amination Catalyzed by Half-Sandwich Iridium Complexes Under Mild Reaction Conditions.

The conversion of aldehydes and ketones to 1° amines could be promoted by half-sandwich iridium complexes using ammonium formate as both the nitrogen and hydride source. To optimize this method for green chemical synthesis, we tested various carbonyl substrates in common polar solvents at physiological temperature (37 °C) and ambient pressure. We found that in methanol, excellent selectivity for the amine over alcohol/amide products could be achieved for a broad assortment of carbonyl-containing compounds. In aqueous media, selective reduction of carbonyls to 1° amines was achieved in the absence of acids. Unfortunately, at Ir catalyst concentrations of <1 mM in water, reductive amination efficiency dropped significantly, which suggest that this catalytic methodology might be not suitable for aqueous applications where very low catalyst concentration is required (e.g., inside living cells).

Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems.

This concept article focuses on the rapid growth of intracellular chemistry dedicated to the integration of small-molecule metal catalysts with living cells and organisms. Although biological systems contain a plethora of biomolecules that can deactivate inorganic species, researchers have shown that small-molecule metal catalysts could be engineered to operate in heterogeneous aqueous environments. Synthetic intracellular reactions have recently been reported for olefin hydrogenation, hydrolysis/oxidative cleavage, azide-alkyne cycloaddition, allylcarbamate cleavage, C-C bond cross coupling, and transfer hydrogenation. Other promising targets for new biocompatible reaction discovery will also be discussed, with a special emphasis on how such innovations could lead to the development of novel technologies and chemical tools.

Intracellular Transfer Hydrogenation Mediated by Unprotected Organoiridium Catalysts.

In the present work, we show for the first time that the conversion of aldehydes to alcohols can be achieved using "unprotected" iridium transfer hydrogenation catalysts inside living cells. The reactions were observed in real time by confocal fluorescence microscopy using a Bodipy fluorogenic substrate. We propose that the reduced cofactor nicotinamide adenine dinucleotide (NADH) is a possible hydride source inside the cell based on studies using pyruvate as a cellular redox modulator. We expect that this biocompatible reductive chemistry will be broadly useful to practitioners working at the interface of chemistry and the life sciences.

Endovascular MR-guided Renal Embolization by Using a Magnetically Assisted Remote-controlled Catheter System.

Purpose To assess the feasibility of a magnetically assisted remote-controlled (MARC) catheter system under magnetic resonance (MR) imaging guidance for performing a simple endovascular procedure (ie, renal artery embolization) in vivo and to compare with x-ray guidance to determine the value of MR imaging guidance and the specific areas where the MARC system can be improved. Materials and Methods In concordance with the Institutional Animal Care and Use Committee protocol, in vivo renal artery navigation and embolization were tested in three farm pigs (mean weight 43 kg ± 2 [standard deviation]) under real-time MR imaging at 1.5 T. The MARC catheter device was constructed by using an intramural copper-braided catheter connected to a laser-lithographed saddle coil at the distal tip. Interventionalists controlled an in-room cart that delivered electrical current to deflect the catheter in the MR imager. Contralateral kidneys were similarly embolized under x-ray guidance by using standard clinical catheters and guidewires. Changes in renal artery flow and perfusion were measured before and after embolization by using velocity-encoded and perfusion MR imaging. Catheter navigation times, renal parenchymal perfusion, and renal artery flow rates were measured for MR-guided and x-ray-guided embolization procedures and are presented as means ± standard deviation in this pilot study. Results Embolization was successful in all six kidneys under both x-ray and MR imaging guidance. Mean catheterization time with MR guidance was 93 seconds ± 56, compared with 60 seconds ± 22 for x-ray guidance. Mean changes in perfusion rates were 4.9 au/sec ± 0.8 versus 4.6 au/sec ± 0.6, and mean changes in renal flow rate were 2.1 mL/min/g ± 0.2 versus 1.9 mL/min/g ± 0.2 with MR imaging and x-ray guidance, respectively. Conclusion The MARC catheter system is feasible for renal artery catheterization and embolization under real-time MR imaging in vivo, and quantitative physiologic measures under MR imaging guidance were similar to those measured under x-ray guidance, suggesting that the MARC catheter system could be used for endovascular procedures with interventional MR imaging. (©) RSNA, 2016.

Multi-detector CT and MRI of microembolized myocardial infarct: monitoring of left ventricular function, perfusion, and myocardial viability in a swine model.

BACKGROUND: Patients with acute myocardial infarct (MI) show additional damage after coronary interventions. PURPOSE: To longitudinally quantify structural and functional changes in the left ventricle (LV) subjected to microembolized MI using multidisciplinary computed tomography (MDCT) and independent reference methods. MATERIAL AND METHODS: Swine (n = 20) served as controls (group I) or were subjected to a combination of coronary occlusion, microembolization, and reperfusion and imaged at 3 days (group II) or 3 days and 5 weeks (group III). LV volumes, perfusion, and MI mass were quantified on cine, perfusion, and delayed contrast enhancement (DE) MDCT. MRI, cardiac injury biomarkers, histochemical and histopathologic stains were used as independent references. RESULTS: MDCT showed a reduction in ejection fraction and increased end systolic volume (31 ± 2% and 82 ± 3 mL, respectively) of group III compared with I (48 ± 2% and 57 ± 1 mL, respectively). It also demonstrated perfusion deficits in microembolized MI and peri-infarcts. DE-MDCT delineated microvascular obstruction (MVO) zones embedded in acute microembolized MI and microinfarct specks resulting from persistent MVO by deposited microemboli in microvessels of peri-infarct zone. Bland-Altman test showed close agreements between the extents of microembolized MI measured on DE-MDCT, DE-MRI, and histochemical TTC staining, but not between these modalities and microscopy. MI resorption was evident between 3 days and 5 weeks (13.4 ± 0.5 g and 9.8 ± 0.5 g, P < 0.017) and histologic examination revealed incomplete healing. Injury biomarkers were increased after intervention. CONCLUSION: MDCT can longitudinally quantify regional perfusion deficits, LV dysfunction, and resorption of microembolized MI. MDCT or MRI can be used alternatively after coronary interventions in cases of contraindications for one modality or the other.

Fine-Tuning Nickel Phenoxyimine Olefin Polymerization Catalysts: Performance Boosting by Alkali Cations.

To gain a better understanding of the influence of cationic additives on coordination-insertion polymerization and to leverage this knowledge in the construction of enhanced olefin polymerization catalysts, we have synthesized a new family of nickel phenoxyimine-polyethylene glycol complexes (NiL0, NiL2-NiL4) that form discrete molecular species with alkali metal ions (M(+) = Li(+), Na(+), K(+)). Metal binding titration studies and structural characterization by X-ray crystallography provide evidence for the self-assembly of both 1:1 and 2:1 NiL:M(+) species in solution, except for NiL4/Na(+) which form only the 1:1 complex. It was found that upon treatment with a phosphine scavenger, these NiL complexes are active catalysts for ethylene polymerization. We demonstrate that the addition of M(+) to NiL can result in up to a 20-fold increase in catalytic efficiency as well as enhancement in polymer molecular weight and branching frequency compared to the use of NiL without coadditives. To the best of our knowledge, this work provides the first systematic study of the effect of secondary metal ions on metal-catalyzed polymerization processes and offers a new general design strategy for developing the next generation of high performance olefin polymerization catalysts.

Multidetector CT measurement of myocardial extracellular volume in acute patchy and contiguous infarction: validation with microscopic measurement.

PURPOSE: To provide proof of concept that expansion of myocardial extracellular volume (MECV), measured at contrast material-enhanced multidetector computed tomography (CT), can be used as a (a) marker for viability based on histologic confirmation and (b) predictor of severity of myocardial injury. MATERIALS AND METHODS: Animals cared for in compliance with Institutional Animal Care and Use Committee served as controls (group 1, n = 6) or were subjected to microinfarction by using 16-mm(3) (60 000 count) microemboli (group 2) and 32-mm(3) (120 000 count) microemboli (group 3), contiguous infarct with left anterior descending artery (LAD) occlusion followed by reperfusion (group 4), or the combination of LAD occlusion and 32-mm(3) microemboli followed by reperfusion (group 5) (n = 7 per group). MECV calculations were based on regional measurements of signal attenuation at contrast-enhanced multidetector CT and counterstaining of infarct at microscopy. Two-way analysis of variance and Student t tests were used to determine significant differences (P < .05). Data were presented as means ± standard deviations. RESULTS: Mean signal attenuation at equilibrium state of contrast media distribution (10 minutes) was significantly different among blood (137 HU ± 10), myocardial muscle (77 HU ± 12, P < .05), and skeletal muscle (35 HU ± 12, P < .05). Patchy microinfarct, contiguous infarct, and microinfarct with preexisting contiguous infarct can be differentiated on the basis of mean MECV (24% ± 3 [group 1] vs 36% ± 3 [group 2], P < .01, and 55% ± 5 [group 4], 56% ± 4 [group 5] vs 41% ± 3 [group 3], P < .05). Microscopy measurements confirmed multidetector CT quantitative measurements and differences in patterns of infarct caused by obstruction of major and minor coronary arteries. Regression analysis revealed excellent correlation between regional MECV using multidetector CT and microscopy (r(2) = 0.92). CONCLUSION: Contrast-enhanced multidetector CT is a suitable noninvasive imaging technique for assessing MECV in acute patchy and contiguous infarct caused by obstruction of major and minor coronary vessels.

Light-induced N2O production from a non-heme iron-nitrosyl dimer.

Two non-heme iron-nitrosyl species, [Fe2(N-Et-HPTB)(O2CPh)(NO)2](BF4)2 (1a) and [Fe2(N-Et-HPTB)(DMF)2(NO)(OH)](BF4)3 (2a), are characterized by FTIR and resonance Raman spectroscopy. Binding of NO is reversible in both complexes, which are prone to NO photolysis under visible light illumination. Photoproduction of N2O occurs in high yield for 1a but not 2a. Low-temperature FTIR photolysis experiments with 1a in acetonitrile do not reveal any intermediate species, but in THF at room temperature, a new {FeNO}(7) species quickly forms under illumination and exhibits a ν(NO) vibration indicative of nitroxyl-like character. This metastable species reacts further under illumination to produce N2O. A reaction mechanism is proposed, and implications for NO reduction in flavodiiron proteins are discussed.

Reference interval evaluation of high-sensitivity troponin T and N-terminal B-type natriuretic peptide in Vietnam and the US: The North South East West Trial.

BACKGROUND: Reference intervals of high-sensitivity troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been determined from Western populations. No data are available regarding expected values in Asian populations. METHODS: A total of 1157 age- and sex-matched healthy individuals (mean age, 41.2 years; 48.0% male) were prospectively enrolled from the US (n = 565) and Vietnam (n = 592). Blood samples were analyzed for hs-cTnT and NT-proBNP. Median values were determined for each country and compared in unadjusted analyses and in analyses adjusted for age, sex, body mass index, study site, race, and vital signs. RESULTS: Median hs-cTnT concentrations were slightly higher for individuals from the US than for those from Vietnam, but both were below the limit of detection (3.7 vs 3.0 ng/L, respectively; P = 0.03). More US participants had an hs-cTnT concentration above the limit of detection (57.2% vs 47.3%; P = 0.001), but the 99th percentile concentration was slightly higher for Asians (US 15.1 vs Vietnam 19.0 ng/L). Concentrations for >98% of both populations were below the standard hs-cTnT 99th percentile of 14.0 ng/L (P = 0.54). Median NT-proBNP concentrations were slightly higher for US participants compared with Vietnamese participants (28 vs 16 ng/L, respectively; P < 0.001). Following adjustment, differences in concentrations of NT-proBNP between healthy US and Vietnamese populations remained significant, whereas for hs-cTnT the differences were no longer significant. Inclusion of hs-cTnT values down to the limit of blank did not change the result. CONCLUSIONS: The differences in hs-cTnT and NT-proBNP between healthy individuals from the US and Vietnam are small. Previously derived reference intervals for both analytes may be applied in Asian populations.

MRI-guided high-intensity focused ultrasound ablation of bone: evaluation of acute findings with MR and CT imaging in a swine model.

PURPOSE: To evaluate hyperacute (<1 hour) changes on magnetic resonance (MR) and computed tomography (CT) imaging following MR-guided high-intensity focused ultrasound (MRgHIFU) in a swine bone model as a function of sonication number and energy. MATERIALS AND METHODS: Experimental procedures received approval from the local Institutional Animal Care and Use Committee. MRgHIFU was used to create distal and proximal ablations in the right femur of eight pigs. Each target was dosed with four or six sonications within similar volumes. The energy dosed to the distal target was higher (419 ± 19 J) than the proximal target (324 ± 17 J). The targeted femur and contralateral control were imaged before and after ablation using MR at 3T. Qualitative changes in signal on T1-weighted, T2-weighted, and T1-weighted postcontrast images were assessed. Ablation dimensions were calculated from postcontrast MRI. The 64-slice CT images were also obtained before and after ablation and qualitative changes were assessed. RESULTS: MRgHIFU bone ablation size measured on average 8.5 × 21.1 × 16.2 mm (transverse × craniocaudal × anteroposterior). Interestingly, within similar prescribed volumes, increasing the number of sonications from 4 to 6 increased the depth of the intramedullary hypoenhanced zone from 2.9 mm to 6.5 mm (P < 0.001). There was no difference in the appearance of low versus high energy ablations. CT imaging did not show structural abnormalities. CONCLUSION: The number of MRgHIFU focal sonications can be used to increase the depth of treatment within the targeted bone. Unlike CT, T2-weighted and contrast-enhanced MR demonstrated the hyperacute structural changes in the femur and surrounding soft tissue.

MRI demonstrates a decrease in myocardial infarct healing and increase in compensatory ventricular hypertrophy following mechanical microvascular obstruction.

PURPOSE: To provide direct evidence that mechanical obstruction of microvessels inhibits infarct resorption (healing) and enhances left ventricular (LV) remodeling using MRI. MATERIALS AND METHODS: Animals (n = 20 pigs) served as controls (group I) or were subjected to either 90 min left anterior descending (LAD) coronary artery occlusion/reperfusion (group II) or 90 min LAD occlusion/ microemboli delivery/reperfusion (group III). MRI (cine and delayed contrast enhanced MRI, DE-MRI) was performed at 3 days and 5 weeks after interventions and used for assessing LV function, mass, and extent of myocardial damage and microvascular obstruction (MVO) using semi-automated threshold method. RESULTS: Persistent MVO in the core of contiguous infarct was larger and more frequent (n = 8/8) in group III than group II (4/8) on DE-MRI at 3 days. Furthermore, patchy microinfarct, as a result of microembolization, was visible as hyperenhanced zone at the borders of the contiguous infarct. The reduction in ejection fraction and increase in LV volumes on cine MRI were greater in group III than group II at 3 days and 5 weeks, which may be attributed to the slow infarct resorption, MVO extents and patchy microinfarct at the borders. CONCLUSION: This MRI study illustrates the recently raised conjecture that MVO delays/inhibits infarct resorption (healing), accentuates LV hypertrophy and pathological remodeling.

A ratiometric substrate for rapid evaluation of transfer hydrogenation efficiency in solution.

A cyclometalated iridium(III) complex bearing a self-immolative quinolinium moiety was developed as a ratiometric substrate for transfer hydrogenation studies. This photoluminescent probe allowed the rapid screening of a variety of Ir catalysts using a microplate reader, offering a convenient method to assess activity using a minimum amount of catalyst sample.

Coronary microemboli effects in preexisting acute infarcts in a swine model: cardiac MR imaging indices, injury biomarkers, and histopathologic assessment.

PURPOSE: To use cardiac magnetic resonance (MR) imaging indices, injury biomarkers, and microscopy for quantifying the effects of defined microemboli volume and sizes on viability, left ventricular (LV) function, and perfusion in preexisting acute myocardial infarcts in a swine model. MATERIALS AND METHODS: Institutional approval was obtained to perform x-ray fluoroscopy and 90-minute left anterior descending coronary artery occlusion-reperfusion (single ischemic insult) in 16 pigs and coronary embolization in eight of the 16 pigs (32 mm(3), 40-120 µm microemboli) (double ischemic insults). Another eight pigs served as controls. Cardiac MR imaging results (viability, function, and perfusion), injury biomarkers (creatine-kinase-MB and troponin I), and histopathologic evaluations were quantified. Analysis of variance was performed, and a P value less than .02 was considered to indicate a significant difference. RESULTS: Delayed contrast material-enhanced MR imaging allowed simultaneous visualization of hyperenhanced large infarcts, hypoenhanced microvascular obstruction (MVO) zones, and moderately enhanced patchy microinfarcts in border zones, which represent different degrees of contraction and perfusion in the respective regions, in pigs subjected to double ischemic insults. The increase in myocardial damage was smaller in pigs with double insults (15.7% ± 1.1% of total LV mass) than in those with a single insult (12.4% ± 1.2%, P < .02), but the reduction in LV ejection fraction was disproportional (32% ± 0.6% and 38% ± 1%, P < .02, respectively). Delayed contrast-enhanced imaging can allow quantification of the MVO zone but can result in underestimation of the extent of myocardial damage compared with microscopy in animals subjected to double insults (18.2 ± 1.6, P < .02). A significant increase in cardiac injury biomarkers was observed at 18-24 hours in both cohorts. The additional effect of microemboli on troponin I was demonstrated at 68-72 hours (3.2 ng/mL ± 0.85 [3.20 µg/L ± 0.85] vs 1.34 ng/mL ± 0.43 [1.34 µg/L ± 0.43], P < .02). CONCLUSION: MR imaging has the potential to allow visualization of acute myocardial infarcts, MVO zones, and patchy microinfarcts simultaneously. The accentuated LV dysfunction caused by double ischemic insults was linked to expansion of the MVO zone, perfusion deficits, and myocardial damage.

Lewis acid-driven self-assembly of diiridium macrocyclic catalysts imparts substrate selectivity and glutathione tolerance.

Molecular inorganic catalysts (MICs) tend to have solvent-exposed metal centers that lack substrate specificity and are easily inhibited by biological nucleophiles. Unfortunately, these limitations exclude many MICs from being considered for in vivo applications. To overcome this challenge, a strategy to spatially confine MICs using Lewis acid-driven self-assembly is presented. It was shown that in the presence of external cations (e.g., Li+, Na+, K+, or Cs+) or phosphate buffered saline, diiridium macrocycles spontaneously formed supramolecular iridium-cation species, which were characterized by X-ray crystallography and dynamic light scattering. These nanoassemblies selectively reduced sterically unhindered C[double bond, length as m-dash]O groups via transfer hydrogenation and tolerated up to 1 mM of glutathione. In contrast, when non-coordinating tetraalkylammonium cations were used, the diiridium catalysts were unable to form higher-ordered structures and discriminate between different aldehyde substrates. This work suggests that in situ coordination self-assembly could be a versatile approach to enable or enhance the integration of MICs with biological hosts.