Co-reporter:Lina A. Basal, Yan Yan, Yimin Shen, E. Mark Haacke, Mohammad Mehrmohammadi, and Matthew J. Allen
ACS Omega March 2017? Volume 2(Issue 3) pp:800-800
Publication Date(Web):March 6, 2017
DOI:10.1021/acsomega.6b00514
We report, for the first time, a multimodal, oxidation-responsive contrast agent for magnetic resonance imaging and photoacoustic imaging that uses the differences in the properties between Eu in the +2 and +3 oxidation states. The enhancement of contrast in T1-weighted magnetic resonance and photoacoustic imaging was observed in the +2 but not in the +3 oxidation state, and the complex is a known chemical exchange saturation transfer agent for magnetic resonance imaging in the +3 oxidation state.Topics: Imaging; Imaging agents; Mechanical properties; Redox reaction; Redox reaction;
Co-reporter:Lina A. Basal;Matthew D. Bailey;Jonathan Romero;Meser M. Ali;Lyazat Kurenbekova;Jason Yustein;Robia G. Pautler
Chemical Science (2010-Present) 2017 vol. 8(Issue 12) pp:8345-8350
Publication Date(Web):2017/11/20
DOI:10.1039/C7SC03142D
Magnetic resonance imaging (MRI) using redox-active, EuII-containing complexes is one of the most promising techniques for noninvasively imaging hypoxia in vivo. In this technique, positive (T1-weighted) contrast enhancement persists in areas of relatively low oxidizing ability, such as hypoxic tissue. Herein, we describe a fluorinated, EuII-containing complex in which the redox-active metal is caged by intramolecular interactions. The position of the fluorine atoms enables temperature-responsive contrast enhancement in the reduced form of the contrast agent and detection of the oxidized contrast agent via MRI in vivo. Positive contrast is observed in 1H-MRI with Eu in the +2 oxidation state, and chemical exchange saturation transfer and 19F-MRI signal are observed with Eu in the +3 oxidation state. Contrast enhancement is controlled by the redox state of Eu, and modulated by the fluorous interactions that cage a bound water molecule reduce relaxivity in a temperature-dependent fashion. Together, these advancements constitute the first report of in vivo, redox-responsive imaging using 19F-MRI.
Co-reporter:Levi A. Ekanger, Devin R. Mills, Meser M. Ali, Lisa A. Polin, Yimin Shen, E. Mark Haacke, and Matthew J. Allen
Inorganic Chemistry 2016 Volume 55(Issue 20) pp:9981-9988
Publication Date(Web):May 31, 2016
DOI:10.1021/acs.inorgchem.6b00629
The 3+ and 2+ oxidation states of europium have drastically different magnetic and spectroscopic properties. Electrochemical measurements are often used to probe EuIII/II oxidation state changes, but a full suite of spectroscopic characterization is necessary to demonstrate conversion between these two oxidation states in solution. Here, we report the facile conversion of an europium(III) tetraglycinate complex into its EuII analogue. We present electrochemical, luminescence, electron paramagnetic resonance, UV–visible, and NMR spectroscopic data demonstrating complete reversibility from the reduction and oxidation of the 3+ and 2+ oxidation states, respectively. The EuII-containing analogue has kinetic stability within the range of clinically approved GdIII-containing complexes using an acid-catalyzed dissociation experiment. Additionally, we demonstrate that the 3+ and 2+ oxidation states provide redox-responsive behavior through chemical-exchange saturation transfer or proton relaxation, respectively. These results will be applicable to a wide range of redox-responsive contrast agents and Eu-containing complexes.
Co-reporter:Guo-Xia Jin, Matthew D. Bailey, and Matthew J. Allen
Inorganic Chemistry 2016 Volume 55(Issue 17) pp:9085
Publication Date(Web):August 22, 2016
DOI:10.1021/acs.inorgchem.6b01659
Two new EuII-containing cryptates were prepared with a new nitrogenous cryptand functionalized with three benzo groups. The introduction of three aromatic rings into the ligand backbone imparts lopsided geometrical features on the resulting EuII coordination environments. In both complexes, the interactions between Eu and the amines on the aromatic side of the molecule are weaker than those on the nonaromatic side, resulting in one discrete unit with two distinct faces. One of the new complexes is, to the best of our knowledge, the first direct observation of a bis-aquo EuII-containing cryptate with two nonadjacent inner-sphere water molecules. In addition to solid-phase structure, the electronic UV–visible and emission spectra of the new complexes were studied in acetonitrile. Experimental results show that the decreased Lewis basicity of the aromatic face hypsochromically shifts absorbances and emissions from a structurally related compound without the benzo groups.
Co-reporter:Akhila N. W. Kuda-Wedagedara; Chengcheng Wang; Philip D. Martin
Journal of the American Chemical Society 2015 Volume 137(Issue 15) pp:4960-4963
Publication Date(Web):April 8, 2015
DOI:10.1021/jacs.5b02506
EuII-containing materials have unique luminescence, redox, and magnetic properties that have potential applications in optoelectronics, sensors, and imaging. Here, we report the synthesis and characterization of EuII-containing aza-222 cryptate that displays yellow luminescence and a quantum yield of 26% in aqueous media. The crystal structure reveals a staggered hula-hoop geometry. Both solid-state and solution-phase data are presented that indicate that the high quantum yield is a result of the absence of OH oscillators in the inner sphere of the complex. We expect that EuII-containing aza-222 cryptate is a step toward EuII-containing luminescent materials that can be used in a variety of applications including biological imaging.
Co-reporter:Levi A. Ekanger and Matthew J. Allen
Metallomics 2015 vol. 7(Issue 3) pp:405-421
Publication Date(Web):12 Jan 2015
DOI:10.1039/C4MT00289J
In magnetic resonance imaging, contrast agents are molecules that increase the contrast-to-noise ratio of non-invasively acquired images. The information gained from magnetic resonance imaging can be increased using responsive contrast agents that undergo chemical changes, and consequently changes to contrast enhancement, for example in response to specific biomarkers that are indicative of diseases. A major limitation with modern responsive contrast agents is concentration-dependence that requires the concentration of contrast agent to be known: an extremely challenging task in vivo. Here, we review advances in several strategies aimed at overcoming the concentration-dependent nature of responsive contrast agents.
Co-reporter:Levi A. Ekanger; Lisa A. Polin;Dr. Yimin Shen; E. Mark Haacke;Dr. Philip D. Martin; Matthew J. Allen
Angewandte Chemie 2015 Volume 127( Issue 48) pp:14606-14609
Publication Date(Web):
DOI:10.1002/ange.201507227
Abstract
The EuII ion rivals GdIII in its ability to enhance contrast in magnetic resonance imaging. However, all reported EuII-based complexes have been studied in vitro largely because the tendency of EuII to oxidize to EuIII has been viewed as a major obstacle to in vivo imaging. Herein, we present solid- and solution-phase characterization of a EuII-containing cryptate and the first in vivo use of EuII to provide contrast enhancement. The results indicate that between one and two water molecules are coordinated to the EuII core upon dissolution. We also demonstrate that EuII-based contrast enhancement can be observed for hours in a mouse.
Co-reporter:Levi A. Ekanger; Lisa A. Polin;Dr. Yimin Shen; E. Mark Haacke;Dr. Philip D. Martin; Matthew J. Allen
Angewandte Chemie International Edition 2015 Volume 54( Issue 48) pp:14398-14401
Publication Date(Web):
DOI:10.1002/anie.201507227
Abstract
The EuII ion rivals GdIII in its ability to enhance contrast in magnetic resonance imaging. However, all reported EuII-based complexes have been studied in vitro largely because the tendency of EuII to oxidize to EuIII has been viewed as a major obstacle to in vivo imaging. Herein, we present solid- and solution-phase characterization of a EuII-containing cryptate and the first in vivo use of EuII to provide contrast enhancement. The results indicate that between one and two water molecules are coordinated to the EuII core upon dissolution. We also demonstrate that EuII-based contrast enhancement can be observed for hours in a mouse.
Co-reporter:Levi A. Ekanger, Meser M. Ali and Matthew J. Allen
Chemical Communications 2014 vol. 50(Issue 94) pp:14835-14838
Publication Date(Web):17 Oct 2014
DOI:10.1039/C4CC07027E
An oxidation-responsive contrast agent for magnetic resonance imaging was synthesized using Eu2+ and liposomes. Positive contrast enhancement was observed with Eu2+, and chemical exchange saturation transfer was observed before and after oxidation of Eu2+. Orthogonal detection modes render the concentration of Eu inconsequential to molecular information provided through imaging.
Co-reporter:Derek J. Averill and Matthew J. Allen
Catalysis Science & Technology 2014 vol. 4(Issue 12) pp:4129-4137
Publication Date(Web):06 Oct 2014
DOI:10.1039/C4CY01117A
Enantioselective bond-forming reactions catalyzed by chiral lanthanide-based complexes are popular because of their Lewis acidity, solvent compatibility, reusability, and potential to catalyze reactions with high stereospecificity. The stereospecific outcomes of bond-forming reactions catalyzed by asymmetric lanthanide-based precatalysts depend on the coordination chemistry of the precatalysts that can be interrogated with X-ray crystal structures, luminescence measurements, NMR spectroscopy, and computational methods. This review is primarily focused on developments related to lanthanide-based precatalysts since the turn of the century and the techniques used to study coordination environments of lanthanide-based precatalysts for Mukaiyama aldol reactions in aqueous media.
Co-reporter:Akhila N. W. Kuda-Wedagedara and Matthew J. Allen
Analyst 2014 vol. 139(Issue 18) pp:4401-4410
Publication Date(Web):23 Jul 2014
DOI:10.1039/C4AN00990H
Contrast agents are diagnostic tools that often complement magnetic resonance imaging. At ultra-high field strengths (≥7 T), magnetic resonance imaging is capable of generating desirable high signal-to-noise ratios, but clinically available contrast agents are less effective at ultra-high field strengths relative to lower fields. This gap in effectiveness demands the development of contrast agents for ultra-high field strengths. In this minireview, we summarize contrast agents reported during the last three years that focused on ultra-high field strengths.
Co-reporter:Lauren E. Hopper, Matthew J. Allen
Tetrahedron Letters 2014 Volume 55(Issue 40) pp:5560-5561
Publication Date(Web):1 October 2014
DOI:10.1016/j.tetlet.2014.08.026
A three-step route was used to synthesize 1,7-bis(t-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane (DO2A-t-Bu ester) from 1,4,7,10-tetraazacyclododecane (cyclen). The overall time of reaction was reduced from a combined ∼56 h to 2.3 h with an overall yield comparable to previously reported methods.
Co-reporter:Zhijin Lin, Matthew J. Allen
Dyes and Pigments 2014 110() pp: 261-269
Publication Date(Web):
DOI:10.1016/j.dyepig.2014.03.020
Co-reporter:Sashiprabha M. Vithanarachchi and Matthew J. Allen
Chemical Communications 2013 vol. 49(Issue 39) pp:4148-4150
Publication Date(Web):09 Nov 2012
DOI:10.1039/C2CC36583A
A multimodal, β-amyloid-targeted contrast agent was synthesized and studied in vitro. The agent has a higher relaxivity than a clinically approved contrast agent and interacts with β-amyloid aggregates producing changes in relaxation rate and fluorescence emission.
Co-reporter:Buddhima N. Siriwardena-Mahanama and Matthew J. Allen
Dalton Transactions 2013 vol. 42(Issue 19) pp:6724-6727
Publication Date(Web):15 Apr 2013
DOI:10.1039/C3DT50885D
We have synthesized a series of LnIII-containing polyethylene glycol conjugates and studied the structural and electronic properties of these complexes. These studies demonstrate that polyethylene glycol can be used to fine-tune water-exchange rates of LnIII-containing polyaminopolycarboxylate-type complexes; this control is desirable in developing LnIII-containing contrast agents for magnetic resonance imaging.
Co-reporter:Jeremiah D. Moore ; Richard L. Lord ; G. Andrés Cisneros
Journal of the American Chemical Society 2012 Volume 134(Issue 42) pp:17372-17375
Publication Date(Web):October 15, 2012
DOI:10.1021/ja307098z
A pH-responsive, luminescent, dimetallic Eu(III)-containing complex has been synthesized and exhibits a unique mechanism of response. The luminescence-decay rate of the complex is slow, due to a lack of water molecules coordinated to the Eu(III) ions. However, the luminescence-decay rate decreases with increasing pH over a biologically relevant range of 4–8. Physical characterization and computational analysis suggest that the pH response is due to protonation of a bridging alkoxide at lower pH values. Modulation of the luminescence-decay rate is independent from the concentration of Eu(III), which we expect to be useful in the non-invasive imaging of in vivo pH.
Co-reporter:Joel Garcia;Akhila N. W. Kuda-Wedagedara
European Journal of Inorganic Chemistry 2012 Volume 2012( Issue 12) pp:2135-2140
Publication Date(Web):
DOI:10.1002/ejic.201101166
Abstract
The kinetic stabilities and relaxivities of a series of Eu2+-containing cryptates have been investigated. Transmetallation studies, which monitored the change in the longitudinal relaxation rate of water protons in the presence of Ca2+, Mg2+, and Zn2+, demonstrated that the cryptate structure influenced the stability, and two of the cryptates studied were inert to transmetallation in the presence of these endogenous ions. The efficacy of these cryptates was determined at different magnetic field strengths, temperatures, and pH values. Cryptate relaxivity was found to be higher at ultrahigh field strengths (7 and 9.4 T) relative to clinically relevant field strengths (1.4 and 3 T), but the efficiency of these cryptates decreased as the temperature increased. In addition, a variation in pH did not yield significant changes in the efficacy of the cryptates. These studies establish a foundation of important properties that are necessary to develop effective positive contrast agents for magnetic resonance imaging from Eu2+-containing cryptates.
Co-reporter:Joel Garcia
European Journal of Inorganic Chemistry 2012 Volume 2012( Issue 29) pp:4550-4563
Publication Date(Web):
DOI:10.1002/ejic.201200159
Abstract
Recent advances in the coordination chemistry of Eu2+ are reviewed. Common synthetic routes for generating discrete Eu2+-containing complexes reported since 2000 are summarized, followed by a description of the reactivity of these complexes and their applications in reduction chemistry, polymerization, luminescence, and as contrast agents for magnetic resonance imaging. Rapid development of the coordination chemistry of Eu2+ has led to an upsurge in the utilization of Eu2+-containing complexes in synthetic chemistry, materials science, and medicine.
Co-reporter:Joel Garcia, Matthew J. Allen
Inorganica Chimica Acta 2012 Volume 393() pp:324-327
Publication Date(Web):1 December 2012
DOI:10.1016/j.ica.2012.07.006
The influence of albumin on the efficacy of a Eu2+-containing complex capable of interacting with human serum albumin (HSA) was investigated at different field strengths (1.4, 3, 7, 9.4, and 11.7 T). Relaxometric measurements indicated that the presence of albumin at higher field strengths (>3 T) did not result in an increase in the relaxivity of the Eu2+ complex, but a relaxation enhancement of 171 ± 11% was observed at 1.4 T. Titration experiments using different percentages (2, 4.5, 6, 10, 15, and 25% w/v) of HSA and variable-temperature 17O NMR measurements were performed to understand the effect of albumin on the molecular properties of the biphenyl-functionalized Eu2+ complex that are relevant to magnetic resonance imaging.Graphical abstractOur graphical abstract depicts our Eu2+ complex interacting with a cartoon version of an albumin protein (HSA). In the process a water molecule is lost and the brightness of the resulting image (from magnetic resonance imaging) is darkened as represented by the images below the cartoon.Highlights► The influence of albumin on a Eu2+-containing complex was investigated. ► Relaxivity increased at 1.4 T relative with albumin. ► Relaxivity decreased at 3, 7, 9.4, and 11.7 T with albumin. ► The number of inner-sphere water molecules decreased in the presence of albumin.
Co-reporter:Yujiang Mei, Derek J. Averill, and Matthew J. Allen
The Journal of Organic Chemistry 2012 Volume 77(Issue 13) pp:5624-5632
Publication Date(Web):June 14, 2012
DOI:10.1021/jo300800b
The development of efficient methods for the asymmetric Mukaiyama aldol reaction in aqueous solution has received great attention. We have developed a new series of chiral lanthanide-containing complexes that produce Mukaiyama aldol products with outstanding enantioselectivities. In this paper, we describe an optimized ligand synthesis, trends in stereoselectivity that result from changing lanthanide ions, and an exploration of substrate scope that includes aromatic and aliphatic aldehydes and silyl enol ethers derived from aromatic and aliphatic ketones.
Co-reporter:Prabani Dissanayake, Yujiang Mei, and Matthew J. Allen
ACS Catalysis 2011 Volume 1(Issue 10) pp:1203
Publication Date(Web):August 24, 2011
DOI:10.1021/cs200213a
Luminescence-decay measurements were studied as a simple and fast technique to determine inner-sphere water coordination numbers of LnIII-based complexes in binary solvent systems that are useful for catalysis. The luminescence-decay rates of EuIII-containing complexes were used to elucidate the coordination environment of EuIII in these solvent systems. Our findings were used to empirically derive easy-to-use equations to determine the average number of inner-sphere water and solvent molecules in binary aqueous solvent systems. The increased knowledge of the inner-sphere coordination environment of catalysts that our equations enable can be used to study lanthanide-catalyzed reactions and new precatalysts.Keywords: catalysis; europium; inner-sphere; lanthanide; luminescence-decay; water-coordination number;
Co-reporter:Joel Garcia, Jaladhar Neelavalli, E. Mark Haacke and Matthew J. Allen
Chemical Communications 2011 vol. 47(Issue 48) pp:12858-12860
Publication Date(Web):02 Nov 2011
DOI:10.1039/C1CC15219J
The relaxivity (contrast-enhancing ability) of EuII-containing cryptates was found to be better than a clinically approved GdIII-based agent at 7 T. These cryptates are among a few examples of paramagnetic substances that show an increase in longitudinal relaxivity, r1, at ultra-high field strength relative to lower field strengths.
Co-reporter:Yujiang Mei ; Prabani Dissanayake
Journal of the American Chemical Society 2010 Volume 132(Issue 37) pp:12871-12873
Publication Date(Web):August 31, 2010
DOI:10.1021/ja107197p
The development of aqueous methods for generating enantiopure β-hydroxy carbonyl compounds is an important goal because these subunits compose many bioactive compounds and the ability to synthesize these groups in water has environmental and cost benefits. In this communication, we report a new class of ligands for aqueous, lanthanide-catalyzed, asymmetric Mukaiyama aldol reactions for the synthesis of chiral β-hydroxy ketones. Furthermore, we have used luminescence-decay measurements to unveil mechanistic information regarding the catalytic reaction via changes in water-coordination number. The precatalysts presented here yielded β-hydroxy carbonyls from aliphatic and aryl substrates with outstanding syn:anti ratios and enantiometric excesses of up to 49:1 and 97%, respectively.
Co-reporter:Nipuni-Dhanesha H. Gamage;Dr. Yujiang Mei;Joel Garcia ; Matthew J. Allen
Angewandte Chemie 2010 Volume 122( Issue 47) pp:9107-9109
Publication Date(Web):
DOI:10.1002/ange.201002789
Co-reporter:Nipuni-Dhanesha H. Gamage;Dr. Yujiang Mei;Joel Garcia ; Matthew J. Allen
Angewandte Chemie International Edition 2010 Volume 49( Issue 47) pp:8923-8925
Publication Date(Web):
DOI:10.1002/anie.201002789
Co-reporter:Prabani Dissanayake
Journal of the American Chemical Society 2009 Volume 131(Issue 18) pp:6342-6343
Publication Date(Web):April 22, 2009
DOI:10.1021/ja900630d
There is tremendous interest in water-compatible lanthanide triflate-based catalysts for carbon−carbon bond forming reactions; however, poor understanding of their aqueous mechanism severely limits the ability to increase the utility of these catalysts. Here, we report dynamic measurements of the water-coordination number of lanthanide triflate-based catalysts using luminescence-decay measurements in a range of aqueous systems. This unique characterization method is a reliable, convenient, and fast approach to analyze lanthanide-based catalysts in aqueous systems.
Co-reporter:Zhijin Lin, Megan L. Shelby, Dugan Hayes, Kelly A. Fransted, Lin X. Chen and Matthew J. Allen
Dalton Transactions 2014 - vol. 43(Issue 43) pp:NaN16159-16159
Publication Date(Web):2014/10/01
DOI:10.1039/C4DT02492C
The first ligand-exchange rate measurements of lanthanide ions in an ionic liquid are reported here. The trend of water-exchange rates in the ionic liquid is the opposite of the trend in water.
Co-reporter:Joel Garcia, Jaladhar Neelavalli, E. Mark Haacke and Matthew J. Allen
Chemical Communications 2011 - vol. 47(Issue 48) pp:NaN12860-12860
Publication Date(Web):2011/11/02
DOI:10.1039/C1CC15219J
The relaxivity (contrast-enhancing ability) of EuII-containing cryptates was found to be better than a clinically approved GdIII-based agent at 7 T. These cryptates are among a few examples of paramagnetic substances that show an increase in longitudinal relaxivity, r1, at ultra-high field strength relative to lower field strengths.
Co-reporter:Buddhima N. Siriwardena-Mahanama and Matthew J. Allen
Dalton Transactions 2013 - vol. 42(Issue 19) pp:NaN6727-6727
Publication Date(Web):2013/04/15
DOI:10.1039/C3DT50885D
We have synthesized a series of LnIII-containing polyethylene glycol conjugates and studied the structural and electronic properties of these complexes. These studies demonstrate that polyethylene glycol can be used to fine-tune water-exchange rates of LnIII-containing polyaminopolycarboxylate-type complexes; this control is desirable in developing LnIII-containing contrast agents for magnetic resonance imaging.
Co-reporter:Sashiprabha M. Vithanarachchi and Matthew J. Allen
Chemical Communications 2013 - vol. 49(Issue 39) pp:NaN4150-4150
Publication Date(Web):2012/11/09
DOI:10.1039/C2CC36583A
A multimodal, β-amyloid-targeted contrast agent was synthesized and studied in vitro. The agent has a higher relaxivity than a clinically approved contrast agent and interacts with β-amyloid aggregates producing changes in relaxation rate and fluorescence emission.
Co-reporter:Levi A. Ekanger, Meser M. Ali and Matthew J. Allen
Chemical Communications 2014 - vol. 50(Issue 94) pp:NaN14838-14838
Publication Date(Web):2014/10/17
DOI:10.1039/C4CC07027E
An oxidation-responsive contrast agent for magnetic resonance imaging was synthesized using Eu2+ and liposomes. Positive contrast enhancement was observed with Eu2+, and chemical exchange saturation transfer was observed before and after oxidation of Eu2+. Orthogonal detection modes render the concentration of Eu inconsequential to molecular information provided through imaging.
Co-reporter:Derek J. Averill and Matthew J. Allen
Catalysis Science & Technology (2011-Present) 2014 - vol. 4(Issue 12) pp:NaN4137-4137
Publication Date(Web):2014/10/06
DOI:10.1039/C4CY01117A
Enantioselective bond-forming reactions catalyzed by chiral lanthanide-based complexes are popular because of their Lewis acidity, solvent compatibility, reusability, and potential to catalyze reactions with high stereospecificity. The stereospecific outcomes of bond-forming reactions catalyzed by asymmetric lanthanide-based precatalysts depend on the coordination chemistry of the precatalysts that can be interrogated with X-ray crystal structures, luminescence measurements, NMR spectroscopy, and computational methods. This review is primarily focused on developments related to lanthanide-based precatalysts since the turn of the century and the techniques used to study coordination environments of lanthanide-based precatalysts for Mukaiyama aldol reactions in aqueous media.