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Chapter 1. PL-Mn+-DTPA 金屬錯合物之合成及特性研究 本報告研
究polylysine(PL)-Mn+-DTPA(diethylenetriaminepentaacetic acid)(
Mn+ =Gd3+, Mn2+ 及Fe3+)的合成及特性,分別改變pH值,溫度,分子量及金
屬濃度百分比,觀察其對弛緩率(relaxivity, R1及R2)之效應. 比較Gd-
DTPA鍵結巨大分子PL與小分子Gd-DTPA之弛緩率,發現弛緩率增加3-4倍,乃
由於轉動相關時間(rotation correlation time)增加故弛緩率隨之增加;
在pH效應方面,當pH值增加弛緩率隨之增加,原因為polylysine之構形由
random coil轉移成 -helix,轉動(tumbling)時間增加所致,至於在作反滴
定時其R1值較正滴定減少大約10%,可能是PL產生二級結構(second order
structure)所致. 另外,在不同溫度對弛緩率之效應方面,隨著溫度之增加
弛緩率隨之減少,乃因溫度增加,轉動相關時間()減少,相對地相關時間()
減少所致,最後在改變不同分子量對弛緩率效應方面,結果顯示分子量由47
kDa改變至300kDa,對弛緩率(R1)影響較小.Chapter 2. DTPA-雙醯胺與
EDTA-雙醯胺及其金屬錯合物之合成,熱力學及弛緩率研究 本報告主要
在探討DTPA(diethylenetriaminepentaacetic acid)及EDTA(
ethylenediamine-tetraacetic acid)衍生物DTPA-BMA(DTPA-bis(
methylamide)),DTPA-BTBA(DTPA-bis(tert-butylamide)),DTPA-BIPA(
DTPA-bis(isopropylamide)),DTPA-BBA(DTPA-bis(benzylamide)),EDTA-
BTBA(EDTA-bis(tert-butylamide)),EDTA-BIPA(EDTA-bis(
isopropylamide)),EDTA-BBA(EDTA-bis(benzylamide))等有機配位子的合
成及其金屬錯合物之熱力學性質及磁性研究. 在熱力學方面,若金屬錯合
物之穩定性較差,即會有游離釓金屬離子與游離有機配位子釋出,此為釓金
屬錯合物毒性之主要來源,且log KML在DTPA-BMA,DTPA-BTBA,DTPA-BIPA及
DTPA-BBA等有機配位子的金屬錯合物中與金屬離子之電荷密度(Z/r)呈一
線性關係. 由不同之pD值對有機配位子溶液之化學位移作圖可進一步說明
由電位滴定中求出之DTPA衍生物之質子化常數. 最後在37及20MHz的磁場
下,研究不同pH值對釓金屬錯合物的自旋-晶格弛緩率的影響,在酸性的範
圍(pH<7)釓金屬錯合物的弛緩率隨著pH值的上升而降低,但是當釓金屬離
子和有機配位子完全形成錯合物時,其R1值便不再改變.
Chapter 1. Synthesis and Characterization of PL-Mn+-DTPA
Complexes The preparation and characteristic of polylysine(
PL)-Mn+-DTPA(diethylenetri-aminepentaacetic acid)(Mn+ = Gd3+,
Mn2+ and Fe3+) complexes was studied. Inaddition, relaxivity of
the PL-M +-DTPA as a function of pH, temperature, wei-ght
percent of metal ion and molecular weight was investigated at
20MHz. Thepolylysine-bound chelates appear to be much more
efficient in increasing the relaxation rates of water than the
free metal complexes. The physical basis of this effect stems
from an increase in the effective correlation, of the
paramagnetic species when it is attached to a slowly tumbling
polylysine mole-cular. The polylysine-Gd-DTPA complexes
exhibited increased relaxivities at20MHz upon raising pH. The
interaction of slow tumbling time at high pH wherethe polylysine
is transformed from random coil to -helix was postulated to
explain the data. The value of R1 at the end of back titration
had droppedabout 10% below its value at the beginning of the
forward titration. One plssible explanation is that the
conditions of the experiment may have causedsome escondary
complex.Chapter 2. Preparation, Thermodynamic and Relaxometry
Studies of Metal Complexes DTPA-bis(amide) and EDTA-
bis(amide) The preparation and some thermodynamic properties
of some gadolinium(III),calcium(II), zinc(II) and copper(II)
complexes of DTPA-bis(amide)(diethylene-triaminepentaacetic
acid-N,N'-bis(amide)) and EDTA-bis(amide)(ethylenediamine-
tetraacetic acid-N,N'-bis(amide)) derivatives, such as DTPA-BMA,
DTPA-BTBA, DTPA-BIPA, DTPA-BBA, EDTA-BTBA, EDTA-BIPAand EDTA-BBA
were studied. In the aspect of thermodynamic, we noted free
gadol-inium ion and free ligand will be released if the
stability constant and selec-tivity constant of the gadolinium
complexes are much lower. The free gadoliniumion and free ligand
are the major source of toxicity. A linear correlation be-tween
log KML(stability constant) and Z/r(charge density on metal ion)
for density on metal ion) for density on metal ion) for DTPA-
BMA, DTPA-BIPA and DTPA-BTBA complexes is consistent with the
lower stabi-lity constant of the Ca2+,Zn2+,Cu2+ vs Gd3+ complex.
The overall selectivityconstants for Gd3+ over other metal ions
were calculated and discussed. Spin-lattice relaxivity(R1,
20MHz) for Gd3+ linear amino carboxylate complexes.The observed
relaxivity values were found to decrease with increase pH in the
acid region below pH7. When Gd3+ complex reached saturated, the
relaxivity va-lue became invariant.and EDTA-BBA were studied. In
the aspect of thermodynamic, we noted free gado-linium ion and
free ligand will be released if the stability constant and sel-
ectivity constant of the gadolinium complexes are much lower.
The free gadoli-nium ion and free ligand are the major source of
toxicity. A linear correlationbetween lof KML(stability
constant) and Z/r(charge density on the metal ion) for DTPA-
BTBA, DTPA-BIPA and DTPA-BMA complexes is consistent with the
lowerstability constant of the Ca(II), Zn(II), Cu(II) vs Gd(III)
complex. The over-all selectivity constants for Gd(III) over
other metal ions were calculated anddiscussed. Spin-lattice
relaxivity(R1, 20MHz) for Gd(III) complexes were measu-red for a
series of Gd(III) linear amino carboxylate complexes. THe
obserbedrelaxivity values were found to decrease with increase
pH in the acid regionbelow pH7. When Gd(III) complex reached
saturated, the relaxivity value becameinvariant.
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