Optimization of the Relaxivity of MRI Contrast Agents:  Effect of Poly(ethylene glycol) Chains on the Water-Exchange Rates of Gd<sup>III</sup> Complexes

Doble, Dan M. J.; Botta, Maurizio; Wang, Jay; Aime, Silvio; Barge, Alessandro; Raymond, Kenneth N.

doi:10.1021/ja011085m

Cited by 92 publications

(124 citation statements)

References 18 publications

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“…Its lower than expected relaxivity is, therefore, a consequence of its lower number of inner sphere water molecule (q = 1). This deduction is in agreement with previous studies [26][27][28] that have demonstrated that long poly(ethyleneglycol) chains almost always displace one water molecule. Moreover, a significant contribution to the total relaxivity results from H-bonded water molecules in the proximity of the paramagnetic center.…”

Section: Relaxivity Of Gd(iii) Complexessupporting

confidence: 93%

“…The observed increase in relaxivity is consistent with previous reports of weak interactions between the small PEG chain and plasma proteins. [26][27][28] The adducts of the Gd(III) complex with the proteins behave as macromolecules which tumble significantly slower; the resulting longer τ R thus increases the relaxivity of the complex.…”

Section: Affinities For Physiological Anionsmentioning

confidence: 99%

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Substituent Effects on Gd(III)-Based MRI Contrast Agents: Optimizing the Stability and Selectivity of the Complex and the Number of Coordinated Water Molecules¹

et al. 2006

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Hydroxypyridinone-based Gd(III) complexes have previously been shown to exhibit high relaxivity, especially at the clinically relevant high magnetic fields relevant for present and future clinical use. This is due to more than one coordinated water molecules that exchange rapidly with bulk solvent.. These complexes, however, present poor water-solubility. Heteropodal complexes which include a terephthalamide moiety maintain the high relaxivity characteristics of the HOPO family and have been functionalized with solubilizing substituents of various charges. The charge of the substituent significantly affects the stability of the Gd(III) complex, with the most stable complex presenting a neutral charge. The solubilizing substituent also moderately affects the affinity of the complex for physiological anions, with the highest affinity observed for the positively charged complex. In any case, only two anions, phosphate and oxalate, measureably bind the Gd(III) complex with weak affinities for these two anions that are comparable to other q=1 complexes and much weaker than DO3A, q=2 based complexes. Furthermore, unlike poly(amino-carboxylate) based complexes, HOPO-based Gd(III) complexes do not show any noticeable interaction with carbonates. The nature of the substituent can also favorably stabilize the coordination of a third water molecule on the Gd(III) center and lead to a nine-coordinate ground state. Such complexes that attain q = 3 incorporate a substituent β to the terminal amide of the TAM podand which are hydrogen-bond acceptors, suggesting that the third water molecule is coordinated to the metal center through a hydrogen-bond network. These substituents include alcohols, primary amines, and acids. Moreover, the coordination of a third water molecule has been achieved without destabilizing the complex.

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Section: Relaxivity Of Gd(iii) Complexessupporting

confidence: 93%

Section: Affinities For Physiological Anionsmentioning

confidence: 99%

Substituent Effects on Gd(III)-Based MRI Contrast Agents: Optimizing the Stability and Selectivity of the Complex and the Number of Coordinated Water Molecules¹

et al. 2006

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“…[47] A key feature of this ligand design is the second amide functionality of the TAM that allows for further derivatization with solubilizing and targeting groups. [49,50] Relaxivities of Gd-HOPO and bis-HOPO-TAM complexes are generally in the range of 7 -13 mM -1 s -1 (20 MHz), and high complex stabilities combined with increased q and optimal water exchange rates make these compounds promising as safe, high-relaxivity agents at high field. The coordination chemistry and relaxometric properties of this class of compounds will be described in the following sections with emphasis on recent work published subsequent to a previous review.…”

Section: Hydroxypyridinone-based Agentsmentioning

confidence: 99%

“…Additionally, it was proposed that the PEG moiety may induce noncovalent interactions with the abundant blood protein HSA to slow tumbling (higher τ R ) and thereby increase relaxivity. [49] The first PEGs chosen for attachment were chains of 44 (21) and 123 (22) ether moieties. Analysis of the NMRD profiles of complexes 21 and 22 indicate a reduction in q relative to the parent q = 2 complex 2, with the best refinements obtained by fixing q to a value of 1.…”

Section: Effect Of Peg Substituentsmentioning

confidence: 99%

High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

et al. 2008

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“…Dentre os lantanídeos, atualmente, o íon gadolínio é o único elemento utilizado clinicamente como agente de contraste. No entanto, outros íons lantanídeos estão sendo investigados para esse fim [56][57][58][59][60][61][62][63] . O íon Gd 3+ é utilizado devido ao fato de ser paramagnético e possuir um momento magnético muito alto; esse é um fator muito importante no efeito de relaxação, pois os íons com maior momento magnético são os mais eficientes nos seus efeitos de relaxação protónica.…”

Section: Medicina: Diagnóstico Não Invasivo (Agentes De Contraste)unclassified

Terras raras: aplicações industriais e biológicas

Martins¹,

Isolani²

2005

Quím. Nova

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Recebido em 30/1/04; aceito em 30/6/04; publicado na web em 5/11/04 RARE EARTHS: INDUSTRIAL AND BIOLOGICAL APPLICATIONS. The history of the rare earths is rich in innovation and these elements have been the object of study of a number of scientists. Rare earths are used practically in almost all aspects of life and these applications are due to their outstanding properties, mainly spectroscopic and magnetic. In industry, the applications of rare earths are many, such as in catalysis, phosphors, magnetism, glass and lasers. In biological systems, rare earths are used, for example, as luminescent probes in the investigation of binding sites in proteins, labels in immunoassays and in noninvasive tests.Keywords: rare earths; spectroscopy; medical applications. INTRODUÇÃOAs terras raras, para as quais se utiliza o símbolo Ln, correspondem aos elementos do lantânio (La, Z = 57) ao lutécio (Lu, Z = 71), entre os quais se incluem o ítrio (Y, Z = 39) e o escândio (Sc, Z = 21). Mas, segundo recomendações da IUPAC 1 , usam-se os termos lantanídeos para designar os elementos do La ao Lu e terras raras quando aos lantanídeos são incluídos o Sc e o Y.A expressão terras raras é imprópria para designar estes elementos, que receberam esta denominação porque foram inicialmente conhecidos em forma de seus óxidos, que se assemelham aos materiais conhecidos como terras. Além da expressão "terras" não ser apropriada à denominação de tais elementos, a expressão "raras" também não está de acordo, pois os lantanídeos são mais abundantes (com exceção do promécio que não ocorre na natureza) do que muitos outros elementos. Por exemplo, os elementos túlio (0,5 ppm) e lutécio (0,8 ppm) que são as terras raras menos abundantes na crosta terrestre, são mais abundantes que a prata (0,07 ppm) e o bismuto (0,008 ppm) 2,3 . O primeiro elemento das terras raras descoberto foi o cério, em 1751, pelo mineralogista suíço A. F. Cronstedt, quando obteve um mineral pesado, a cerita. Porém, existem controvérsias quanto a este fato e atribui-se o ano de 1787 como o início da história das terras raras, quando Carl Axel Arrhenius encontrou um mineral escuro, a iterbita (também conhecido como gadolinita), em uma pequena vila, Ytterby, próxima a Estocolmo 2 . Por constituírem uma família que apresenta propriedades físicas e químicas semelhantes, exigindo um trabalho imenso para separá-los com a obtenção de espécies relativamente puras, este grupo de elementos foi pouco explorado durante anos e somente em 1907 é que praticamente todas as terras raras naturais foram conhecidas 4-9 . A industrialização das terras raras teve início com a fabricação de camisas de lampiões. Com o passar do tempo suas propriedades foram tornando-se mais conhecidas e seus compostos passaram a ser mais utilizados, tais como na produção de "mischmetal" para pedras de isqueiro, baterias recarregáveis e aplicações metalúrgicas 5,10 . Com o desenvolvimento tecnológico as terras raras passaram a ganhar novos usos e, hoje em dia, o universo de suas aplicações é muito abrangente, sendo utiliz...

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Optimization of the Relaxivity of MRI Contrast Agents: Effect of Poly(ethylene glycol) Chains on the Water-Exchange Rates of Gd^III Complexes

Cited by 92 publications

References 18 publications

Substituent Effects on Gd(III)-Based MRI Contrast Agents: Optimizing the Stability and Selectivity of the Complex and the Number of Coordinated Water Molecules¹

Substituent Effects on Gd(III)-Based MRI Contrast Agents: Optimizing the Stability and Selectivity of the Complex and the Number of Coordinated Water Molecules¹

High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

Terras raras: aplicações industriais e biológicas

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Optimization of the Relaxivity of MRI Contrast Agents: Effect of Poly(ethylene glycol) Chains on the Water-Exchange Rates of GdIII Complexes

Cited by 92 publications

References 18 publications

Substituent Effects on Gd(III)-Based MRI Contrast Agents: Optimizing the Stability and Selectivity of the Complex and the Number of Coordinated Water Molecules1

Substituent Effects on Gd(III)-Based MRI Contrast Agents: Optimizing the Stability and Selectivity of the Complex and the Number of Coordinated Water Molecules1

High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

Terras raras: aplicações industriais e biológicas

Contact Info

Product

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Optimization of the Relaxivity of MRI Contrast Agents: Effect of Poly(ethylene glycol) Chains on the Water-Exchange Rates of Gd^III Complexes

Substituent Effects on Gd(III)-Based MRI Contrast Agents: Optimizing the Stability and Selectivity of the Complex and the Number of Coordinated Water Molecules¹

Substituent Effects on Gd(III)-Based MRI Contrast Agents: Optimizing the Stability and Selectivity of the Complex and the Number of Coordinated Water Molecules¹