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S H Koenig

Publications and source records attributed to S H Koenig.

At least 55 records · Page 3Linked to original sources
PubMed1990

Oligomerization and conformation change in solutions of calf lens gamma II-crystallin. Results from 1/T1 nuclear magnetic relaxation dispersion profiles.

From analyses of the magnetic field dependence of 1/T1 (nuclear magnetic relaxation dispersion [NMRD] profiles) of water protons in solutions of highly purified calf lens gamma II-crystallin, we find that monomers form oligomers at relatively low concentrations, which increase in size with increasing concentration and decreasing temperature. At approximately 16% by volume and -4 degrees C, the mean oligomeric molecular weight is approximately 120-fold greater than the monomeric value of 20 kD. Below this concentration, there is no indication of any substantive change in conformation of the monomeric subunits. At higher concentrations, the tertiary structure of the monomer appears to reconfigure rather abruptly, but reversibly, as evidenced by the appearance of spectra-like 14N peaks in the NMRD profiles. The magnitudes of these peaks, known to arise from cross-relaxation of water protons through access to amide (NH) moieties of the protein backbone, indicate that the high concentration conformation is not compact, but open and extended in a manner that allows enhanced interaction with solvent. The data are analogous to those found for homogenates of calf and chicken lens (Beaulieu, C. F., J. I. Clark, R. D. Brown III, M. Spiller, and S. H. Koenig. 1988. Magn. Reson. Med. 8:47-57; Beaulieu, C. F., R. D. Brown III, J. I. Clark, M. Spiller, and S. H. Koenig. 1989. Magn. Reson. Med. 10:62-72). This unusually large dependence of oligomeric size and conformation on concentration in the physiological range is suggested as the mechanism by which osmotic equilibrium is maintained, at minimal metabolic expense, in the presence of large gradients of protein concentration in the lens in vivo (cf Vérétout and Tardieu, 1989. Eur. Biophys. J. 17:61-68). Finally, the results of the NMRD data provide a ready explanation of the low temperature phase transition, and "cold-cataract" separation of phases, observed in gamma II-crystallin solutions; we suggest that the phases that separate are the two major conformers detected by NMRD.

Animals↗
PubMed1990

Magnetic field dependence of 1/T1 of human brain tumors. Correlations with histology.

The authors have measured the magnetic field dependence of 1/T1 (nuclear magnetic relaxation dispersion, or NMRD profiles) of water protons of histologically characterized samples of astrocytomas, meningiomas, and lymphomas. The goal was to elucidate the determinants of 1/T1 of brain tumors at the cellular level and, in particular, to search for a possible correlation of the profiles with neoplastic properties, including degree of malignancy. Because of the recently demonstrated contribution of myelin to 1/T1 of white matter, careful histologic analyses were performed to correct for its presence. The range of magnitude of the profiles of differing types and grades of tumors correlates with the range of water content of these tumors; the correlation of water content with cellularity (density of cell nuclei in a histologic preparation), in turn, produces correlations of 1/T1 with tumor type. For all the tumors studied, 1/T1 is proportional to solids content; the constant of proportionality is relatively insensitive to tumor type and, for astrocytomas, grade of malignancy; and is about the same as that of normal gray matter. For low- and intermediate-grade astrocytomas that contain myelin, the myelin-specific contribution to 1/T1 has to be considered to make manifest the underlying correlations, which are best demonstrated at low fields, where the background contribution of water and dissolved oxygen is minimal. At high fields, where most imaging is done, a change in oxygen partial pressure, as for example from ischemia in very malignant tumors, is sufficient to alter 1/T1 significantly, reducing the intrinsic correlation between histology and 1/T1.

Astrocytoma↗
PubMed1990

Paramagnetic agents as tracers in magnetic resonance imaging. Extrapolations from Gd-DTPA to everything.

The range of compounds, both paramagnetic and ferromagnetic, with potential utility as tracers for enhancing contrast in magnetic resonance imaging is very large. Fortunately, the changes in 1/T1 and 1/T2 of water protons in solution--and ultimately in tissue--induced by these agents arise from variations of only a few physical parameters. In the present work, we first consider the properties of Gd-DTPA2- in solution in some detail, including its effects on both inner and outer sphere relaxation of solvent protons. Then, by varying one or another physical parameter, we derive behavior that characterizes several classes of contrast agents with markedly different properties. These include small macrocycles, such as Gd-DOTA-; larger complexes, including oligomers and conjugates of small paramagnetic complexes with protein; magnetized particles, such as magnetite, as a function of their size; and highly anisotropic porphyrin compounds. Predictions are compared with data from the literature.

Contrast Media↗
PubMed1989

Evaluation of polyaza macrocyclic methylene phosphonate chelates of Gd3+ ions as MRI contrast agents.

Gd(DTPA)2- (diethylenetriaminepentaacetic acid) and the polyaza macrocyclic Gd(DOTA)- (1,4,7,10-tetraazacyclododecane-N,N',N'',N''') are paradigms of general purpose paramagnetic complexes useful for enhancing contrast in magnetic resonance imaging (MRI). It is of both fundamental and practical interest to determine how one might modify the chemical structure of these chelate complexes to improve their utility for MRI in specific circumstances. In the present work, we investigated polyaza methylene phosphonate complexes of Gd3+ ions to compare their NMRD profiles with those of their carboxylate analogs and with Gd(DTPA)2-. We find that the number q of exchangeable water molecules coordinated directly to the Gd3+ ions tends to be smaller in the phosphonates, in principle reducing their utility in MRI. However, these phosphonates have a tendency to oligomerize, and the resulting decrease in rotational mobility of the paramagnetic oligomers increases their relaxivity at higher fields, offsetting the effect of decreases in q. In particular, Gd(DOTRP)3- (1,5,9-triazacyclododecane-N,N',N'',-tris(methylenephosphonic++ + acid] would be an increasingly effective contrast agent above approximately 10 MHz if the oligomerization was stable in vivo (and the Gd3+ ions were sufficiently well bound). At lower fields, the relaxivity of these small chelate complexes is dominated by tau S0, the relaxation time of the spin moments of the paramagnetic ions. We find this to be favorably long for complexes of Gd3+ with the macrocyclic phosphonate ligands, as was found earlier by us for Gd(DOTA)-. This situation, ostensibly related to the relatively high symmetry and rigidity of the macrocyclic complexes, can increase the low-field relaxivity of the phosphonates almost a factor of 2 beyond that of Gd(DTPA)2-.

Chelating Agents↗
PubMed1989

Relaxometry of lens homogenates. II. Temperature dependence and comparison with other proteins.

We have extended our earlier work (C.F. Beaulieu, J.I. Clark, R.D. Brown III, M. Spiller, and S.H. Koenig, Magn. Reson. Med. 8, 45 (1988] on the magnetic field dependence of 1/T1 (NMRD profiles) of calf lens nuclear homogenates, at 25 degrees C, to 5 degrees C, and to other protein systems as well. These include concentrated solutions of myoglobin and bovine serum albumin, both globular proteins, the first compact and roughly spherical, the other extended, flexible, and with weak internal bonding; chicken lens homogenate, for which the dominant crystallins (lens proteins) are approximately 70% alpha-helical compared with calf crystallins, which are essentially all beta-sheet; and hen egg white, both native and heat-denatured. Our earlier conjectures regarding a reversible change in protein organization of the calf lens crystallins as a function of solute protein concentration is given added support. Our findings suggest that cytoplasmic homogenate can be characterized as a heterogeneous and polymorphic solution of crystallins. At high concentrations the NH moieties of the protein backbone become accessible to solvent with water (not NH proton) exchange rates greater than 10(4) s-1. This conclusion is based on two aspects of the observed NMRD profiles. At low crystallin concentration, the profiles of calf and chicken lens homogenates are similar in form to those of myoglobin and native hen egg white, a form that has been studied previously for a range of diamagnetic globular proteins and has been demonstrated to arise from the rotational thermal motion of the solute molecules. At high crystallin concentrations, the NMRD profiles of the lens homogenates develop a monotonic background (high rates at low fields), much like that of the heat-denatured egg-white sample and those of most tissues. In addition, there is a set of peaks in the central part of the profiles of the concentrated crystallins, seen also in the denatured egg white and some tissues but not in the myoglobin sample, which is known to arise from cross-relaxation interactions between the water protons and (through the intermediary of the NH proton) the 14N quadrupolar levels. The magnitude of these peaks, which is larger by an order of magnitude for native calf lens homogenates than for any tissue, requires that the majority of the NH moieties be accessible to water. Finally, going to 5 degrees C for the native calf lens homogenate takes the sample below the temperature of reversible phase separation, and it becomes opaque.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Sources of the increased longitudinal relaxation rates observed in melanotic melanoma. An in vitro study of synthetic melanins.

Researchers have suggested that the increased longitudinal relaxation rates (1/T1) of solvent water protons often found in melanoma result either from the paramagnetism of stable free radicals occurring in melanin or from that of methemoglobin in nonacute hemorrhagic regions of the tumor. However, field-cycling relaxometry and model solutions of synthetic melanin produced data which show that free radicals in melanin do not contribute significantly to 1/T1; instead, aggregation of melanin into macromolecular particles and binding of biologically-common paramagnetic metal ions (ie Fe3+, Mn2+, and Cu2+) to melanin effectively do increase 1/T1. These data have been combined with published histochemical data on melanin-containing tissues, while disregarding any additional effect related to hemorrhage. The result indicates that in melanoma the expected contribution of melanin-bound Fe3+ to 1/T1, at typical imaging fields, predominates under estimated in vivo conditions; furthermore, the total contribution from all sources, specifically due to the presence of melanin, is sufficient to account for reported measurements of 1/T1 in melanoma. Comparing the latter results with published data on T1 relaxation in model solutions of methemoglobin suggests that co-existing regions of nonacute microhemorrhage also may contribute significantly to 1/T1 under certain conditions. Finally, the implications for 1/T2 of melanin occurring in vivo within discrete melanosomes is discussed.

Chemical Phenomena↗
PubMed1988

Relaxivity and binding of Mn2+ ions in solutions of phosphatidylserine vesicles.

We report the magnetic field dependence (NMRD profiles) of 1/T1 of solvent protons in solutions of unilamellar phosphatidylserine vesicles with added Mn2+ ions, including studies of the variation of the profiles with temperature, extent of coverage of available binding sites by Mn2+ ions, ionic strength, and competition with (nonparamagnetic) Ca2+ ions. ions. In addition, we sketch the theory of screening of the negative surface charges of the vesicles due to both specific binding of Mn2+ ions and nonspecific effects of other mobile solute ions. The major result is that the NMRD profiles, although qualitatively similar, vary systematically as the parameters of the solutions are altered, in a manner consistent with the theory of screening. The profiles of the Mn2+-vesicle complexes are much like those of Mn2+-protein complexes that have the ions in an octahedral ligand environment. In addition, we find that the profiles are similar to those reported for Mn2+ ions in packed liver cells and liver tissue, supporting a previous conjecture that available Mn2+ in liver binds to the polar head groups of cell membranes, saturating these sites before binding elsewhere. Again, it is evident that results for in vitro model systems can be extrapolated reliably to tissue behavior.

Contrast Media↗
PubMed1988

Relaxometry of calf lens homogenates, including cross-relaxation by crystallin NH groups.

We studied the magnetic field dependence of the longitudinal relaxation rates of water protons (1/T1 nuclear magnetic relaxation dispersion (NMRD) profiles) in transparent homogenates of calf lens. The samples included nuclear homogenates with total (heterogeneous) crystallin contents between 34% (v/v) (native) and 14% (diluted) as well as cortical homogenate, 21% (native) and 34% (concentrated). The NMRD profiles had two components: a monotonic dispersive component (analogous to that of both globular protein solutions and diamagnetic tissue) and "14N quadrupolar peaks." 14N peaks have never been reported for protein solutions, only for tissues and dehydrated proteins. These peaks occur between 0.5 and 5 MHz proton Larmor frequency and arise from interactions of solvent water protons with NH moieties of proteins. The 14N peaks in lens cytoplasm are very large and may correlate with the crystallin structure and interactions required to maintain short-range order and lens transparency. The monotonic and 14N quadrupolar components were largest in concentrated samples, but with different concentration dependencies. The dispersive components of samples above approximately 19% protein concentration had a fixed functional form, the amplitude of which varied with protein volume fraction, f, by the multiplicative factor f/(1 - f), suggesting spatial organization and dynamics of the solute proteins that are relatively independent of water content. In contrast, at concentrations less than 19%, the NMRD profiles are concentration dependent, indicating a dependence of the orientational relaxation time of the proteins on protein-protein interactions seen previously in other globular proteins at these concentrations. The 14N peaks are not resolved below approximately 19% protein and increase linearly with incremental volume fraction at protein concentrations above 19%. In addition, the 14N peaks in nuclear homogenates are 50-100% larger than those of cortical homogenates at the same concentrations. Partial substitution of solvent D2O for H2O decreases the peak heights, indicating that an exchangeable proton mediates the interaction between solvent protons and protein 14N nuclei.

Animals↗
PubMed1988

Number of inner-sphere water molecules in Gd3+ and Eu3+ complexes of DTPA-amide and -ester conjugates.

The inner-sphere water coordination number for Eu3+ and Gd3+ complexed with five DTPA analogs, in which one or two terminal carboxylate groups are functionalized as propyl amides or propyl esters, have been studied using phosphorescence lifetime and nuclear magnetic relaxation dispersion (NMRD) measurements. Both methods show that the water coordination number does not increase above that observed for the analogous DTPA complexes. The phosphorescence lifetime results indicate that all five Eu3+ complexes have one inner-sphere water molecule at 25 degrees C. The NMRD profiles for three of the Gd3+ complexes at 25 degrees C are also consistent with one inner-sphere water molecule, whereas two complexes have profiles consistent only with a mixture of complexes, 50% containing a single water molecule and 50% with none. Lowering the temperature alters the population of these species such that all five Gd3+ complexes have significantly less bound water on average at 5 degrees C. These results explain the anomalous temperature dependencies of the NMRD curves reported previously for the Gd(DTPA)-protein conjugates. We suggest that the Gd(DTPA)-conjugate systems have a fluxional coordination sphere whereby the amount of inner-sphere coordinated water varies from near zero at 5 degrees C to a high of two near 37 degrees C.

Chemical Phenomena↗
PubMed1988

Longitudinal proton relaxation rates in rabbit tissues after intravenous injection of free and chelated Mn2+.

The factors that determine the field-dependent increase in 1/T1 of tissue water protons were investigated for MnCl2 and Mn2+ (PDTA) (1,3-propylenediamine-N,N',N'',N'''-tetraacetic acid) introduced intravenously into rabbits. Mn2+ was used in preference to other paramagnetic ions in part because of the distinct NMRD profiles (magnetic field dependence of 1/T1) of free Mn2+ ions, their small chelate complexes, and their macromolecular conjugates, and in part because the relatively low toxicity of Mn2+ is favorable for animal studies. Tissue content of Mn2+ was determined in all samples by inductively coupled plasma analyses the state of Mn2+ in excised tissues was determined from the form of the 1/T1 NMRD profile of water protons; and distribution of contrast agent within tissue and access of water on a T1 time scale were determined by double-exponential analyses of proton relaxation behavior in intact doped tissue, as well as by the change of single-exponential relaxation rates and proton signal intensity upon gentle disruption of the tissue. MnCl2 is found in all tissues, except fat and skeletal muscle, but liver is most avid at low dose, and Mn2+ accumulates in spleen after high doses. Chelation targets Mn2+ to liver and kidney, saturating the liver chemically at relatively low dose. We suggest that pronounced increase in tissue relaxivity results from irrotationally bound Mn2+, ostensibly associated with the polar head groups of cell membranes. Compartmentalization of contrast agent and restricted diffusion of tissue water influences the maximum relaxation rates attainable, so that there is an optimal dose of these contrast agents which is rather low.

Animals↗
PubMed1988

Theory of relaxation of mobile water protons induced by protein NH moieties, with application to rat heart muscle and calf lens homogenates.

Kimmich and co-workers (cf., Winter, F., and R. Kimmich. 1982. Biochim. Biophys. Acta. 719:292-298) discovered peaks in the magnetic field-dependent longitudinal relaxation rate (1/T1) of water protons of muscle tissue, cells, and dehydrated protein in the field range 0.5-5 MHz (proton Larmor frequency), and argued that the peaks resulted from cross relaxation associated with quadrupolar splittings of the 14N nuclei of protein NH groups. More recently, analogous peaks were found in homogenates of calf eye lens (Beaulieu, C.F., J.I. Clark, R.D. Brown III, M. Spiller, and S. H. Koenig, 1987. Abstr. Soc. Magn. Res. Med., 6th, New York. 598-599), which are essentially concentrated protein solutions, and were measured with sufficient precision to allow resolution of the relaxation spectra into several peaks and the intrinsic linewidths to be determined. Here, we analyze these relaxation spectra, as well as earlier data on rat heart (Koenig, S. H., R. D. Brown III, D. Adams, D. Emerson, and C. G. Harrison. 1984. Invest. Radiol. 19:76-81) in some detail, and suggest a specific pathway for the cross relaxation to which we apply the theory of relaxation quantitatively. The view that emerges is that, at fields such that the proton Zeeman energy of the NH protons matches an 14N quadrupolar splitting, relaxation of these protons is by cross relaxation to the 14N nuclei which in turn transfer excess energy to the protein. The correlation time for the NH proton interaction is the T2 of the 14N nuclei, approximately 10(-6) s, whereas T1 of the NH protons is approximately 1.25 ms. At these energy level crossings, the NH protons become relaxation sinks for protons of rapidly exchanging (-3 x 109 s-1) water molecules hydrogen bonded to the same backbone carbonyl oxygens as the NH protons. The lifetime of this hydrogen bond (-3 x 10-10 s) then becomes the correlation time for the water proton-NH proton interaction which, though short, is much longer than the analogous correlation time (-5 x 10-12 s) in pure water; the enhanced interaction results in peaks in the field-dependent 1/ T, of the solvent protons. There are few data on the lifetime of such bonds, but the results here conform with the recent considerations of Bennett, H. F., R. D. Brown III, S. H. Koenig, and H. M. Swartz. 1987. Magn. Reson. Med. 4:93-111, regarding hydrogen bond lifetimes for water molecules bound to macromolecules. The recent precise field-dependent relaxation data, here combined with both a quantitative theory and the fact that the magnitude of the 14N peaks is very concentration sensitive, allow, at least for lens proteins, a study of protein-protein interactions difficult to investigate by other methods.

Amines↗
PubMed1988

Transverse relaxation (1/T2) of solvent protons induced by magnetized spheres and its relevance to contrast enhancement in MRI.

At typical imaging fields, the transverse relaxation rates 1/T2 of the protons of soft tissue are much greater than their longitudinal rates 1/T1. Because of this, clinical magnetic resonance images are generally collected using relatively short values of TR, an approach that both increases comfort for the patient and reduces medical costs. As a result, image contrast is dominated by the 1/T2 values of the tissue protons. Currently, small single-ion paramagnetic complexes--Gd-DTPA is the prime example--are being used to enhance contrast in clinical magnetic resonance imaging (MRI). However, such agents contribute comparably to 1/T1 and 1/T2 so that their utility is greatest when introduced into body fluids, for which 1/T1 and 1/T2 are also comparable; they are much less useful for enhancing contrast of soft tissue. For this, one must look elsewhere, to rather large aggregates of paramagnetic ions, which may either be paramagnetic or ferromagnetic. Iron in its many chemical and biochemical forms, both exogenous and endogenous, is important in this respect. Its presence in ferritin and hemosiderin--in excess in some diseases--is one example; deoxyhemoglobin in cells and methemoglobin in blood pools from trauma are others in which endogenous iron in several oxidation states is important. Magnetic particulates of various iron oxides are now being used as exogenous agents for enhancing 1/T2 preferentially at imaging fields. Predicting contrast enhancement under such circumstances can become rather complex, not because the theory is difficult, but because the underlying concepts are subtle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Electron paramagnetic resonance and magnetic susceptibility studies of dimanganese concanavalin A. Evidence for antiferromagnetic exchange coupling.

The double Mn2+ complex of concanavalin A with bound saccharide (SMMPL) was examined by electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements. A room temperature X-band (9 GHz) EPR spectrum of SMMPL revealed a relatively weak, broad resonance in contrast to the spectrum with a six-line hyperfine-split pattern observed for the mononuclear, high-spin Mn2+ complex found in Ca2+-Mn2+-concanavalin A with saccharide present (SCMPL). The EPR spectrum of SMMPL at 77 K, however, consisted of a series of overlapping patterns of 11 hyperfine-split lines near g = 2.0 with members of each pattern separated by 47 G, half the value of the hyperfine splitting of SCMPL. These 11-line patterns are preserved at Q-band (35 GHz), indicating that the manganese ions in SMMPL form a spin-coupled, binuclear center. As expected for an exchange-coupled system, the EPR signal of SMMPL at 77 K saturates at a higher microwave power than those for SCMPL or Mn2+ aquoion. There is also a marked loss of EPR signal intensity for SMMPL between 4.2 and 1.4 K, which supports the view that the pair of manganese ions is exchanged-coupled. The temperature dependence of both the magnetic susceptibility and the low-temperature EPR spectral intensity can be explained by a model in which the two high-spin Mn2+ ions of SMMPL are antierromagnetically exchanged-coupled with an isotropic coupling constant J = 1.8 cm-1 (for the spin Hamiltonian Hex = JS1.S2). Zero-field splitting D' was estimated to be 375 G from the EPR spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Concanavalin A↗
PubMed1987

Tissue distribution and stability of metalloporphyrin MRI contrast agents.

Mn(III), Fe(III), and Gd(III) complexes of tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and several other porphyrins were evaluated as potential MRI contrast agents. Based on consideration of relaxivity and stability properties in solution, MnTPPS was found to be the compound of choice. At pH 7 the Gd and Mn complexes significantly enhanced the water proton relaxation rate, while the relaxivity of FeTPPS exhibited a significant loss of relaxivity above pH 6 due to oxy-dimer formation. Although GdTPPS exhibited the highest relaxivity in solution, this property was rapidly lost due to dissociation of the metal ion. By contrast MnTPPS remained stable in human plasma after incubation for 9 days. Upon intravenous injection into athymic mice bearing subcutaneous human colon carcinoma xenografts, MnTPPS provided enhanced relaxation of the tissue water in several excised mouse tissues, notably kidney, liver, and tumor. The results at a fixed field (0.25 T) and relaxation dispersion studies showed decreases in water relaxation rates with time for kidney and liver, but an increase for the tumor, with a maximum near 4 days at the highest dose used.

Animals↗
PubMed1987

Effects of nitroxides on the magnetic field and temperature dependence of 1/T1 of solvent water protons.

We report a study of the longitudinal NMRD profiles (proton longitudinal relaxation rates as a function of field strength) over a broad range of magnetic field (0.01 to 50 MHz proton Larmor frequency) and temperature (-9.6 to 37 degrees C) for aqueous solutions of (i) a fatty acid-nitroxide/albumin complex and (ii) 10 low molecular weight nitroxides. Analysis of the NMRD profile for the fatty acid-nitroxide/albumin complex provides a lower bound estimate for the rotational correlation time of the complex, which permits the calculation of an upper bound on the inner sphere contribution to relaxation of the uncomplexed nitroxides. Inner sphere processes, ostensibly due to water molecules hydrogen bonded to the nitroxide moiety, dominate the relaxation effects of the slowly rotating macromolecular nitroxide/albumin complex. By extrapolation, the contribution of these inner sphere processes are negligible for rapidly tumbling nitroxides free in solution, which affect solvent proton relaxation almost entirely through outer sphere processes (i.e., translational diffusion). A comparison of the relaxation data for aqueous solutions of the uncomplexed nitroxides with the theory of outer sphere relaxation of J.H. Freed (J. Chem. Phys. 68, 4034 (1978] yields values for the distance of closest approach of the water and nitroxide molecules, as well as for their relative diffusion constants, at five different temperatures. Our results indicate that the rather modest relaxivities of aqueous solutions of nitroxides increase substantially with increased solvent viscosity and with protein binding, supporting the potential utility of nitroxides for enhancement of contrast in nuclear magnetic resonance images.

Cyclic N-Oxides↗
PubMed1987

The anomalous relaxivity of Mn3+ (TPPS4).

It was recently reported (C-W. Chen et al., FEBS Lett. 168, 70 (1984)) that water solutions of Mn3+ (TPPS4) have a surprisingly high relaxivity at 20 MHz and 37 degrees C, greater than most Mn2+ complexes including the hexaaquoion. Because Mn3+ (TPPS4) is highly stable, and porphyrins in general are tumor-seeking, we have sought to understand the origin of the large relaxivity by comparing the 1/T1 NMRD profiles (magnetic field dependence of 1/T1 of solvent protons) of Mn3+ (TPPS4) solutions with those of a number of other small Fe3+ and Mn2+ complexes. By relating the measured NMRD profiles to the theory of relaxation by magnetic dipolar interactions, in a form appropriate for small paramagnetic solute molecules, we establish that the theory affords an excellent quantitative description of the relaxation behavior of all the samples, and confirm that the relaxivity of Mn3+ (TPPS4) is anomalously high. The effect is attributed, in part, to the anisotropy of the ground-state wavefunction of Mn3+ in the porphyrin complex, effectively bringing the spin density of the Mn3+ ions closer to the protons of the coordinated water molecules than would a spherically symmetric S-state ion. In addition, the paramagnetic relaxation time of the Mn3+ spins, though short, is longer than would be anticipated for a non-S-state ion, and increases substantially with magnetic field above about 2 MHz. In this regard, Mn3+ (TPPS4) may be one of a class of molecules with properties particularly favorable for use as contrast-enhancing agents in magnetic resonance imaging.

Ions↗