Side Chain Entropy and the Activation of Organocobalamins for Carbon−Cobalt Bond Homolysis:  Synthesis, Characterization, and Thermolysis of the Neopentyl Derivative of a Unique Cobalamin Analog Lacking a <i>c</i> Side Chain

Brown, Kenneth L.; Cheng, Shifa; Zubkowski, Jeffrey D.; Valente, E.

doi:10.1021/ic961378u

Cited by 13 publications

(6 citation statements)

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“…A notable feature of the biological chemistry of the AdoCbl-dependent enzymes is the tremendous rate enhancement of the homolysis of Co–C β imparted by the protein, which has been reported − to be >10 12 . How this rate enhancement is effected is still the subject of considerable interest.…”

Section: Introductionmentioning

confidence: 99%

DFT Studies of Trans and Cis Influences in the Homolysis of the Co–C Bond in Models of the Alkylcobalamins

et al. 2013

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Density functional theory (DFT) calculations (BP86/6-31+G(d,p)) and an analysis of the electron density using Bader's quantum theory of atoms in molecules (QTAIM) are used to explore factors that influence the bond dissociation energy (BDE) of the Co-C bond in models for the cofactor in the coenzyme B12-dependent enzymes. An increase in the basicity of L in [L-Co(III)(corrin)-CH3](n+), L = NH3, NH2(-), and NH(2-), causes an elongation of the trans Co-C bond, but this does not necessarily cause the BDE to decrease. The bond between the metal and the N-donor of L, Co-Nα, usually becomes shorter after Co-C homolysis as the resulting five-coordinate product permits the metal ion to move toward L. This contraction increases with the basicity of L and stabilizes the five-coordinate product. The BDE is found to correlate well with two variables, the basicity of L and the difference in the Co-Nα bond length between the five-coordinate product and the six-coordinate ground state. When L is a naturally occurring amino acid or a model for its metal-coordinating side chain, the BDE is found to be moderately dependent on L and decrease with an increase in the softness of the donor atom of L. Sulfides produce a BDE < 30 kcal mol(-1), whereas neutral alcohol donors produce a stronger Co-C bond with a BDE of 34-35 kcal mol(-1). All other ligands are associated with a trans Co-C bond that is almost invariant in strength and with a BDE of 31-33 kcal mol(-1). Models of the type [H3N-Co(III)(N4)-CH3](n+), where N4 = bis(dimethylglyoxime), porphyrin, corrin, and corrole, show that the nature of the tetraaza equatorial ligand can change BDE values by over 8 kcal mol(-1); the BDE when N4 = bis(dimethylglyoxime) is significantly larger than for the other three systems, among which differences in BDE are quite small (2.4 kcal mol(-1)). The differential stabilization of the five-coordinate product by the shrinking of the Co-Nα bond (in corrin and in corrole) or its elongation (in porphyrin and in bis(dimethylglyoxime)) is an important factor in determining the BDE of these systems. Corrin has the longest and weakest Co-C bond; this, together with a significant contraction of the Co-Nα after homolysis, is likely to be the origin of its relatively low BDE.

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Section: Introductionmentioning

confidence: 99%

DFT Studies of Trans and Cis Influences in the Homolysis of the Co–C Bond in Models of the Alkylcobalamins

et al. 2013

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“…The crystal structures of AdoCbl ( 9 ) and (α-ribo)AdoCbl were used as the starting point for modeling. Hydrogen atoms were placed in standard positions using ALCHEMY III . A set of parabolic potential functions of the form U nOe ( r ij ) = k nOe ( r ij − r ° ij ) 2 were added to simulate the interproton distances, r ij , determined from the two-dimensional (2D) ROESY spectra.…”

Section: Methodsmentioning

confidence: 99%

“…Hydrogen atoms were placed in standard positions using ALCHEMY III. 4 A set of parabolic potential functions of the form U nOe (r ij ) ) k nOe (r ij -r°i j ) 2 were added to simulate the interproton distances, r ij , determined from the two-dimensional (2D) ROESY spectra. On the basis of Clore et al (47), the restraining force constant, k nOe , was defined as k B TS/2(∆ ( ij ) 2 , where k B is Boltzman's constant, T the absolute temperature, S a scaling factor, and ∆ ( ij the positive and negative error estimates of r ij .…”

Section: Methodsmentioning

confidence: 99%

“…The 5′-deoxyadenosylcobalamin (AdoCbl 1 )-requiring enzymes catalyze a series of intramolecular 1,2-rearrangements or the reduction of ribonucleotides to deoxyribonucleotides. The initial enzymatic step in each case is the cleavage of the carbon-cobalt bond of the coenzyme, a reaction catalyzed by these enzymes by as much as 10 12 -fold (1)(2)(3)(4). While the mechanisms by which these enzymes achieve this catalysis are not at all clear, distortion of AdoCbl by the enzyme is thought to play a role (5)(6)(7).…”

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“…Hyperchem Inc., Gainseville, FL 4. Tripos Associates, St. Louis, MO.FIGURE 3: Superposition (at the four equatorial nitrogens) of the crystal structure of (R-ribo)AdoCbl (dark line, both conformers) and the crystal structure of AdoCbl (light line; 9).Structure and Activity of a Novel Analogue of Coenzyme B 12Biochemistry, Vol.37, No.…”

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Structural and Enzymatic Studies of a New Analogue of Coenzyme B₁₂ with an α-Adenosyl Upper Axial Ligand

et al. 1998

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A new analogue of coenzyme B12 (5'-deoxyadenosylcobalamin, AdoCbl), in which the configuration of the N-glycosidic bond in the Ado ligand is inverted [(alpha-ribo)AdoCbl], has been synthesized and its crystal structure determined by X-ray diffraction [MoKalpha, lambda = 0.71073 A, monoclinic P212121, a = 16.132(12) A, b = 21. 684(15) A, c = 27.30(3) A, 9611 independent reflections, R1 = 0. 0708]. As suggested by molecular mechanics modeling before the structure was known, the Ado ligand lies over the southern quadrant of the molecule, as is the case for AdoCbl. The most striking feature of the structure is disorder in the orientation of the adenine (Ade) moiety relative to the ribose of the Ado ligand. This was resolved with a two-state model in which in the major (0.57 occupancy) conformer the A16(O)-A11-A9(N)-A8 dihedral angle is 1.9 degrees and the Ade is virtually perpendicular to the corrin ring; in the minor conformer, the Ade is tilted down, and this dihedral is -48.7 degrees. The Co-C and axial Co-N bond lengths and the Co-C-C bond angle are quite similar to those in AdoCbl. The corrin ring is considerably flatter than that of AdoCbl, with a fold angle of 11.7 degrees. The molecule was successfully modeled by molecular mechanics (MM), and rotation of the Ado ligand relative to the corrin gave rise to four locally minimum structures with the Ado in the southern, eastern, northern, or western quadrant, with the southern conformation as the global minimum, as is the case with AdoCbl itself. Nuclear Overhauser effects (nOe's) observed by two-dimensional (2D) NMR were incorporated as restraints in molecular dynamics (MD) and simulated annealing (SA) calculations. A MD simulation at 300 K showed that only the southern conformation is populated with the Ado ligand confined to an arc from over C15 to over C12, while the Ade ring oscillates from perpendicular to parallel to the corrin ring. Twenty-seven structures were collected by MD-SA. Most of these annealed into the southern conformation, but examples of the other conformations were also found. The new analogue is a partially active coenzyme for the ribonucleotide reductase from Lactobacillus leichmanii with maximal activity that is 9.7% of that of AdoCbl itself, and a very high Km value (245 microM compared to 0.54 microM for AdoCbl). In addition, the rate constant for enzyme-induced carbon-cobalt bond cleavage of (alpha-ribo)AdoCbl is 160-fold smaller than that for AdoCbl, and only 1/3 as much cob(II)alamin is produced at the active site.

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Probing the Nature of the Co^IIIIon in Cobalamins − Spectroscopic and Structural Investigations of the Reactions of Aquacobalamin (Vitamin B_12a) with Ambident Nucleophiles

et al. 2003

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The rate of substitution of the H2O β‐ligand in aquacobalamin (vitamin B12a) is surprisingly fast for CoIII. This may arise as a result of transfer of electron density to CoIII by the corrin, conferring on the metal atom a softer and more labile character, and would require electronic communication between the equatorial ligand and the axial coordination sites of the metal atom. We have substituted H2O in B12a with the ambidentate nucleophiles SCN−, SeCN−, NO2− and S2O32−, examined the UV/Vis spectra of the resultant complexes, crystallised them, and determined their structures by X‐ray diffraction methods. The UV/Vis spectra of these complexes, as well as those of H2OCbl+, SO3Cbl− and MeCbl, were fitted by Gaussian functions. The principal bands move to lower energy in response to an increase in donation of electron density from the axial ligand, demonstrating direct electronic communication between the axial and the equatorial ligands. In the solid state, the thiocyanato ligand in SCNCbl is coordinated through N, although 13C NMR spectroscopy shows that the complex exists as a mixture of two linkage isomers in solution. SeCN−, NO2− and S2O32− are coordinated through the softer available donor in each case (Se, N and S, respectively). There is a regular ground‐state trans effect such that as the donor power of the β‐ligand increases, the trans Co−Nax bond length increases. A survey of the structures available in the CSD shows that this preference for the softer donor atom in ambidentate nucleophiles is not unusual in CoIII complexes. The Co−N bond length in SCNCbl is marginally long for coordination to CoIII, but the axial bond lengths of the other complexes are as expected. Hence, whereas the corrin macrocycle clearly imparts lability on CoIII, presumably by transfer of electron density onto the metal atom, this is insufficient to have a major effect on the ground‐state structures of its complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

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Side Chain Entropy and the Activation of Organocobalamins for Carbon−Cobalt Bond Homolysis: Synthesis, Characterization, and Thermolysis of the Neopentyl Derivative of a Unique Cobalamin Analog Lacking a c Side Chain

Cited by 13 publications

References 103 publications

DFT Studies of Trans and Cis Influences in the Homolysis of the Co–C Bond in Models of the Alkylcobalamins

DFT Studies of Trans and Cis Influences in the Homolysis of the Co–C Bond in Models of the Alkylcobalamins

Structural and Enzymatic Studies of a New Analogue of Coenzyme B₁₂ with an α-Adenosyl Upper Axial Ligand

Probing the Nature of the Co^IIIIon in Cobalamins − Spectroscopic and Structural Investigations of the Reactions of Aquacobalamin (Vitamin B_12a) with Ambident Nucleophiles

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Side Chain Entropy and the Activation of Organocobalamins for Carbon−Cobalt Bond Homolysis: Synthesis, Characterization, and Thermolysis of the Neopentyl Derivative of a Unique Cobalamin Analog Lacking a c Side Chain

Cited by 13 publications

References 103 publications

DFT Studies of Trans and Cis Influences in the Homolysis of the Co–C Bond in Models of the Alkylcobalamins

DFT Studies of Trans and Cis Influences in the Homolysis of the Co–C Bond in Models of the Alkylcobalamins

Structural and Enzymatic Studies of a New Analogue of Coenzyme B12 with an α-Adenosyl Upper Axial Ligand

Probing the Nature of the CoIIIIon in Cobalamins − Spectroscopic and Structural Investigations of the Reactions of Aquacobalamin (Vitamin B12a) with Ambident Nucleophiles

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Product

Resources

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Structural and Enzymatic Studies of a New Analogue of Coenzyme B₁₂ with an α-Adenosyl Upper Axial Ligand

Probing the Nature of the Co^IIIIon in Cobalamins − Spectroscopic and Structural Investigations of the Reactions of Aquacobalamin (Vitamin B_12a) with Ambident Nucleophiles