Lanthanide induced nuclear magnetic resonance shifts.  Structural and computational study

Wing, Richard M.; Uebel, J. J.; Andersen, Kell K.

doi:10.1021/ja00799a036

Cited by 69 publications

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“…To further understand the structure-function relationship implied by the importance of the la-hydroxyl for biological activity, we have undertaken a detailed analysis of the expected dynamic topology of vitamin D3, its metabolites, and analogs in solution by high-resolution proton magnetic resonance spectroscopy in conjunction with lanthanide-induced shift studies (20,32). Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1 for structures of these and related compounds.) Already both la,25-(OH)2D3 and its analog la-OHD3 have been found to be clinically useful in treating patients with chronic renal failure (31), a disease in which there is a possible derangement of the renal enzyme 25-OH-vitamin D3-la-hydroxylase.To further understand the structure-function relationship implied by the importance of the la-hydroxyl for biological activity, we have undertaken a detailed analysis of the expected dynamic topology of vitamin D3, its metabolites, and analogs in solution by high-resolution proton magnetic resonance spectroscopy in conjunction with lanthanide-induced shift studies (20,32). Fig.…”

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Vitamin D: Concerning the Relationship Between Molecular Topology and Biological Function

Okamura

Norman

Wing

1974

Proc. Natl. Acad. Sci. U.S.A.

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Structure-function relationships for vitamin D1, its metabolites, and analogs are discussed with particular emphasis on the A-ring conformation. It is emphasized that the A-ring of these seco-steroids consists of a pair of rapidly equilibrating chair conformers. As a consequence, different chair conformations produce different orientations of substituent groups in the A-ring. It is propbsed that the la-hydroxyl of la,25-dihydroxyvitamin D3 or its geometric equivalent in analogs must occupy the equatorial, as opposed to the axial, orientation for optimization of biological activity. This proposal is discussed in relation to existing published data on struc- (0,10). The biochemical mode of action of la,25-(OH)2D3 (11) is believed to occur as a consequenee of association with cytoplasmic and nuclear receptors, as is the case for other classical steroid hormones (12, 13) such as estrogen (14), hydrocortisone (15), aldosterone (16), or Abbreviations: D3, vitamin D3; 25-OHD3, 25-hydroxyvitamin D3; 1a,25-(OH)2D3, la,25-dihydroxyvitamin D3; la-OHD3, lahydroxyvitamin D3; 5,6-t-D3, 5,6-trans-vitamin D3; H2T, dihydrotachysterol; i-T, isotachysterol; H2V-IV, dihydrovitamin D-IV; 3-d-la-OHD3, 3-deoxy-lc-hydroxyvitamin D3; 3-d-la,25-(OH)2D3, 3-deoxy-la,25-dihydroxyvitamin D3; 3a!-or 3,8-Me-3-d-la-OHD3, 3a-or 3,3-methyl-3-deoxy-1a-hydroxyvitamln D3; the subscript 3 or 2 after the letters D, T, and V refer to vitamin D-like molecules containing the cholesterol side-chain carbon skeleton as in vitamin D3 or the ergosterol side-chain carbon skeleton as in vitamin D2, respectively. The abbreviation H2T instead of DHT for dihydrotachysterol is used since the former is more in keeping with the rules of IUB and IUPAC.* Send all correspondence to the first author. A preliminary account of this work was presented at the 1974 meetings of the American Society of Biological Chemists in Minneapolis, Minn. (see ref. 20). This is paper V in the series, "Studies on Vitamin D and Its Analogs." Paper IV is Norman, A. W., Mitra, M. N., Okamura, W. H. & Wing, R. M., "Vitamin D: 3-Deoxy-lahydroxyvitamin D3, a biologically active analog of la,25-dihydroxyvitamin D3," Science, in press. testosterone (17). In fact, the fat-soluble vitamin D3 should be considered a steroid hormone both from a structural and a functional point of view (18).The unusual importance of the 1a-hydroxyl to the active metabolite was emphasized by the observation that neither the parent vitamin D3 nor the intermediate 25-hydroxyvitamin D3 (25-OHD3) weie able to produce any stimulation of intestinal calcium transport in nephrectomized rats, while 1a,25-(OH)2D3 was fully active (19). The importance of. the lai-hydroxyl to biological activity is further emphasized by the observed high biological activity of the chemically synthesized analogs, 3-deoxy-la-OH-vitamin D3 (3-d-la-OH-D3) (20) and la-hydroxyvitamin D3 (la-OHD3) (21-25), and the pseudo-la-hydroxyl § analogs, 5,6-trans-vitamin D3 (5,6-t-D3) (26), dihydrotachysterol3 (H2T3) (27-29), and isotachysterol3 (i-T3) (30)...

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confidence: 99%

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Vitamin D: Concerning the Relationship Between Molecular Topology and Biological Function

Okamura

Norman

Wing

1974

Proc. Natl. Acad. Sci. U.S.A.

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“…As distâncias interatômicas foram calculadas com um desvio médio de 0,12Å ou 4% (Tabela 6). Os ângulos de 23,26 . O poliedro de coordenação deste complexo é definido por treze arestas e sete distâncias em relação ao Eu 3+ , podendo ser visualizado como um octaedro em que uma das pirâmides foi substituída por uma cunha (Fig.…”

Section: Teste Do Modelounclassified

“…Testamos a robustez das gaussianas, utilizando o mesmo conjunto de oito parâmetros, no cálculo de três outros complexos de Eu(III), já utilizados anteriormente, com estruturas cristalográficas conhecidas: [Eu(dpm) 3 .dmto], n.c.-sete 26 , [Eu(acac) 3 .o-phen], n.c.-oito 15 e [Eu(dpm) 3 .terpy] n.c.-nove 24 , para os quais também obtivemos uma grande redução nos desvios médios das distâncias centrais (metal -ligante) da primeira esfera de coordenação (Tabela 14). Todavia, os desvios médios das arestas dos poliedros de cordenação foram menos sensíveis à introdução das gaussianas, havendo pequena redução para o [Eu(dpm) 3 .dmto] e pequenos aumentos para os outros dois complexos (Tabela 14).…”

Section: Adição De Gaussianas Ao Modelounclassified

Uma metodologia para o projeto teórico de conversores moleculares de luz

Andrade¹,

Costa²,

Simas³

et al. 1998

Quím. Nova

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“…SuFtes cycliques. en conformation chaise it S=O tq7 A 13 (Tubleau 4). Les rksultats expCrimentaux sont moins homogknes qu'avec les sulfites chaises a S=O ax.…”

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Déplacements chimiques induits en RMN par un réactif lanthanidique: I—Application á l'analyse conformationnelle de sulfites cycliques

1976

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Abstract-The chemical shifts induced by Eu(fod), in several series of 6-membered cyclic sulfites give the parameters Kc and A S R of the complexation equilibrium for an assumed 1 : I stoicheiometry. The equilibrium constant Kc decreases with increasing bulk of the C-4 and C-6 substituents and polarity of the C-5 substituent, which corresponds to the increase of the i.r. stretching frequency vS=O. Thus axial S=O will be more tightly complexed than equatorial S=O. It can be predicted that when a conformational equilibrium exists without shift reagent, displacement towards an axial S=O form will occur with the reagent. Use of the A S R pseudocontact equation confirms the following: (i) ax S=O chair forms are stabilized; (ii) eq S=O chairs with two eq C-4 and C-6 substituents show an equilibrium with a few percent of the ax S=O flexible conformation, particularly in the absence of an ax C-5 substituent; (iii) twist forms with a 2-5 axis, intermediate S=O and tr-uns-4, 6-di-tert-Bu substituents give a boat form with 0 at the prow and ax S-0 ; (iv) the conformational equilibrium of trans-5-trrt-butyl-2-0x0-1, 3 , 2-dioxathiane (chair with ax tert-Bu and S=O CT 70%) is completely displaced towards that form; (v) ris-4,4,6-trimethyl-2-oxo-l,3,2-dioxathiane, which exists as an equilibrium in which the three types of S=O occur, is complexed essentially in the twist form with a 1-4 axis and ax S-0.Most of these results are supported by the coupling constants analysis for the ratio R,/S, = I . Rksumk-Les dtplacements chimiques induits par Eu(fod), sur plusieurs series de sulfites cycliques a six chainons permettent de dCterminer les parametres K , et AsR de I'tquilibre de complexation pour une stoechiometrie supposee 1 : 1. La constante d'tquilibre apparente Kc decrolt lorsque la substitution en 4 et 6 et la polarite du substituant en 5 augmentent en relation avec une augmentation de la frequence d'elongation vS=O en infrarouge. Ainsi, le groupe S-0 ax s'associera plus fortement que S=O tq. Lorsqu'un equilibre conformationnel existe en l'absence de reactif lanthanidique, on peut prevoir qu'il evoluera avec h i vers une forme S=O ax. L'exploitation des AsR a I'aide de 1'6quation de pseudocontact confirme ces previsions: (i) les formes chaises a S=O ax sont stabilisees; (ii) les chaises a S=O Cq avec deux substituants eq en 4 et 6 presentent un equilibre avec quelques pourcents de conformation flexible a S=O ax, surtout en l'absence de substituant ax en 5; (iii) les formes croisees d'axe 2-5 a S=O intermediaire et f-Bu trans en 4 et 6 Cvoluent vers un bateau 0 en proue et S=O ax;(iv) le t-Bu-5 0x02 dioxathianne-l,3,2 trans, chaise A t-Bu et S=O axiaux pour -70%, a son equilibre conformationnel complttenient deplace vers cette forme; (v) le trimethyl-4,4,6 0x0-2 dioxathianne-l,3,2 cis, Cquilibre oh interviennent les trois types de S=O, s'associe essentiellement en conformation croisee d'axe 1-4 et a groupe S=O ax. La plupart de ces resultats ont tte Btayes par l'analyse des constantes de couplage pour le rapport R,/S, = 1.

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Lanthanide induced nuclear magnetic resonance shifts. Structural and computational study

Cited by 69 publications

References 0 publications

Vitamin D: Concerning the Relationship Between Molecular Topology and Biological Function

Vitamin D: Concerning the Relationship Between Molecular Topology and Biological Function

Uma metodologia para o projeto teórico de conversores moleculares de luz

Déplacements chimiques induits en RMN par un réactif lanthanidique: I—Application á l'analyse conformationnelle de sulfites cycliques

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