2 research outputs found
DFT Computational Study of the Methanolytic Cleavage of DNA and RNA Phosphodiester Models Promoted by the Dinuclear Zn<sup>(II)</sup> Complex of 1,3-Bis(1,5,9-triazacyclododec-1-yl)propane
A density functional
theory study of the cleavage of a DNA model
[<i>p</i>-nitrophenyl methyl phosphate (<b>2</b>)]
and two RNA models [<i>p</i>-nitrophenyl 2-hydroxypropyl
phosphate (<b>3</b>) and phenyl 2-hydroxypropyl phosphate (<b>4</b>)] promoted by the dinuclear Zn<sup>(II)</sup> complex of
1,3-bisĀ(1,5,9-triazacyclododec-1-yl)Āpropane formulated with a bridging
methoxide (<b>1a</b>) was undertaken to determine possible mechanisms
for the transesterification processes that are consistent with experimental
data. The initial substrate-bound state of <b>2</b>:<b>1a</b> or <b>3</b>:<b>1a</b> has the two phosphoryl oxygens
bridging Zn<sup>(II)</sup><sub>1</sub> and Zn<sup>(II)</sup><sub>2</sub>. For each of <b>2</b> and <b>3</b>, four possible mechanisms
were investigated, three of which were consistent with the overall
free energy for the catalytic cleavage step for each substrate. The
computations revealed various roles for the metal ions in the three
mechanisms. These encompass concerted or stepwise processes, where
the two metal ions with associated alkoxy groups [Zn<sup>(II)</sup><sub>1</sub>:(<sup>ā</sup>OCH<sub>3</sub>) and Zn<sup>(II)</sup><sub>1</sub>:(<sup>ā</sup>O-propyl)] play the role of a direct
nucleophile (on <b>2</b> and <b>3</b>, respectively) or
where Zn<sup>(II)</sup><sub>1</sub>:(<sup>ā</sup>OCH<sub>3</sub>) can act as a general base to deprotonate an attacking solvent molecule
in the case of <b>2</b> or the attacking 2-hydroxypropyl group
in the case of <b>3</b>. The Zn<sup>(II)</sup><sub>2</sub> ion
can serve as a spectator (after exerting a Lewis acid role in binding
one of the phosphatesā oxygens) or play active additional roles
in providing direct coordination of the departing aryloxy group or
positioning a hydrogen-bonding solvent to assist the departure of
the leaving group. An important finding revealed by the calculations
is the flexibility of the ligand system that allows the ZnāZn
distance to expand from ā¼3.6 Ć
in <b>1a</b> to over
5 Ć
in the transforming <b>2</b>:<b>1a</b> and <b>3</b>:<b>1a</b> complexes during the catalytic event
Trifunctional Metal Ion-Catalyzed Solvolysis: Cu(II)-Promoted Methanolysis of <i>N</i>,<i>N</i>ābis(2-picolyl) Benzamides Involves Unusual Lewis Acid Activation of Substrate, Delivery of Coordinated Nucleophile, Powerful Assistance of the Leaving Group Departure
The methanolyses of CuĀ(II) complexes of a series of <i>N</i>,<i>N</i>-bisĀ(2-picolyl) benzamides (<b>4a</b>ā<b>g</b>) bearing substituents X on the aromatic ring
were studied
under <sub>s</sub><sup>s</sup>pH-controlled
conditions at 25 Ā°C. The active form of the complexes at neutral <sub>s</sub><sup>s</sup>pH has a stoichiometry
of <b>4</b>:CuĀ(II):(<sup>ā</sup>OCH<sub>3</sub>)Ā(HOCH<sub>3</sub>) and decomposes unimolecularly with a rate constant <i>k</i><sub><i>x</i></sub>. A Hammett plot of logĀ(<i>k</i><sub><i>x</i></sub>) vs Ļ<sub><i>x</i></sub> values has a Ļ<sub><i>x</i></sub> of 0.80
Ā± 0.05. Solvent deuterium kinetic isotope effects of 1.12 and
1.20 were determined for decomposition of the 4-nitro and 4-methoxy
derivatives, <b>4b</b>:CuĀ(II):(<sup>ā</sup>OCH<sub>3</sub>)Ā(HOCH<sub>3</sub>) and <b>4g</b>:CuĀ(II):(<sup>ā</sup>OCH<sub>3</sub>)Ā(HOCH<sub>3</sub>), in the plateau region of the <sub>s</sub><sup>s</sup>pH/logĀ(<i>k</i><sub><i>x</i></sub>) profiles in both CH<sub>3</sub>OH and CH<sub>3</sub>OD. Activation parameters for decomposition
of these complexes are Ī<i>H</i><sup>ā§§</sup> = 19.1 and 21.3 kcal mol<sup>ā1</sup> respectively and Ī<i>S</i><sup>ā§§</sup> = ā5.1 and ā2 cal K<sup>ā1</sup> mol<sup>ā1</sup>. Density functional theory
(DFT) calculations for the reactions of the CuĀ(II):(<sup>ā</sup>OCH<sub>3</sub>)Ā(HOCH<sub>3</sub>) complexes of <b>4a,b</b> and <b>g</b> (<b>4a</b>, X = 3,5-dinitro) were conducted
to probe the relative transition state energies and geometries of
the different states. The experimental and computational data support
a mechanism where the metal ion is coordinated to the <i>N</i>,<i>N</i>-bisĀ(2-picolyl) amide unit and positioned so that
it permits delivery of a coordinated CuĀ(II):(<sup>ā</sup>OCH<sub>3</sub>) nucleophile to the Cī»O in the rate-limiting transition
state (TS) of the reaction. This proceeds to a tetrahedral intermediate <i><b>INT</b></i>, occupying a shallow minimum on the free
energy surface with the CuĀ(II) coordinated to both the methoxide and
the amidic N. Breakdown of <i><b>INT</b></i> is a
virtually barrierless process, involving a CuĀ(II)-assisted departure
of the bisĀ(2-picolyl)Āamide anion. The analysis of the data points
to a trifunctional role for the metal ion in the solvolysis mechanism
where it activates intramolecular nucleophilic attack on the Cī»O
group by coordination to an amidic N in the first step of the reaction
and subsequently assists leaving group departure in the second step.
The catalysis is very large; compared with the second order rate constant
for methoxide attack on <b>4b</b>, the computed reaction of
CH<sub>3</sub>O<sup>ā</sup> and <b>4b</b>:CuĀ(II):(HOCH<sub>3</sub>)<sub>2</sub> is accelerated by roughly 2.0 Ć 10<sup>16</sup> times