5 research outputs found
Cu(II)-Ion-Catalyzed Solvolysis of <i>N,N-</i>Bis(2-picolyl)ureas in Alcohol Solvents: Evidence for Cleavage Involving Nucleophilic Addition and Strong Assistance of Bis(2-picolyl)amine Leaving Group Departure
The
kinetics and products for solvolysis of <i>N</i>-<i>p</i>-nitrophenyl-<i>N</i>ā²,<i>N</i>ā²-bisĀ(pyridin-2-ylmethyl) urea (<b>7a</b>), <i>N</i>-methyl-<i>N</i>-<i>p</i>-nitrophenyl-<i>N</i>ā²,<i>N</i>ā²-bisĀ(pyridin-2-yl methyl)
urea (<b>7b</b>), and <i>N</i>-phenyl-<i>N</i>ā²,<i>N</i>ā²-bisĀ(pyridin-2-yl-methyl) urea
(DPPU) (<b>7c</b>) promoted by CuĀ(II) ion in methanol and ethanol
were studied under <sub>s</sub><sup>s</sup>pH-controlled conditions at 25 Ā°C. Methanolysis and ethanolysis
of these substrates proceeds rapidly at a 1:1 ratio of substrate:metal
ion, the half-times for decomposition of the CuĀ(II):<b>7a</b> complexes being ā¼150 min in methanol and 15 min in ethanol.
In all cases, the reaction products are the CuĀ(II) complex of bisĀ(2-picolyl)Āamine
and the <i>O</i>-methyl or <i>O</i>-ethyl carbamate
of the parent aniline, signifying that the point of cleavage is the
bisĀ(2-picolyl)īøNīøCī»O bond. Reactions of the CuĀ(II):<b>7b</b> complexes in each solvent proceed about 3ā5 times
slower than their respective CuĀ(II):<b>7a</b> complexes, excluding
an elimination mechanism that proceeds through an isocyanate which
subsequently adds alcohol to give the observed products. The reactions
also proceed in other solvents, with the order of reactivity ethanol
> methanol >1-propanol >2-propanol > acetonitrile (with
0.2% methanol)
> water spanning a range of 150-fold. The mechanism of the reactions
is discussed, and the reactivity and mode of cleavage are compared
with that of the MĀ(II)-promoted ethanolytic cleavage of a mono-2-picolyl
derivative, <i>N</i>-<i>p</i>-nitrophenyl-<i>N</i>ā²-(pyridin-2-yl-methyl) urea (<b>4a</b>),
which had previously been shown to cleave at the aniline NāCī»O
bond. The large estimated acceleration of the rate of attack of ethoxide
on <b>7b</b> of at least 2 Ć 10<sup>16</sup> provided by
associating CuĀ(II) with the departing group in this urea is discussed
in terms of a trifunctional role for the metal ion involving Lewis
acid activation of the substrate, intramolecular delivery of a CuĀ(II)-coordinated
ethoxide, and metal-ion-assisted leaving group departure
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
Rapid Ni, Zn, and Cu Ion-Promoted Alcoholysis of <i>N</i>,<i>N-</i>Bis(2-picolyl)- and <i>N</i>,<i>N-</i>Bis((1<i>H</i>ābenzimidazol-2-yl)methyl)ā<i>p</i>ānitrobenzamides in Methanol and Ethanol
The methanolysis and ethanolysis
of the NiĀ(II), ZnĀ(II), and CuĀ(II)
complexes of <i>N</i>,<i>N</i>-bisĀ(2-picolyl)-<i>p</i>-nitrobenzamide (<b>1</b>) and <i>N</i>,<i>N</i>-bisĀ((1<i>H</i>-benzimidazol-2-yl)Āmethyl)-<i>p</i>-nitrobenzamide (<b>2</b>) were studied under pH-controlled
conditions at 25 Ā°C. Details of the mechanism were obtained from
plots of the <i>k</i><sub>obs</sub> values for the reaction
under pseudo-first-order conditions as a function of [M<sup>2+</sup>]. Such plots give saturation kinetics for the CuĀ(II)-promoted reactions
of <b>1</b> and <b>2</b> in both solvents, the ZnĀ(II)-promoted
reaction of <b>1</b> in methanol, and the ZnĀ(II)- and NiĀ(II)-promoted
reactions of <b>2</b> in methanol and ethanol. Logs of the maximal
observed rate constants obtained from the latter plots, (<i>k</i><sub>obs</sub><sup>max</sup>), when
plotted versus <sub>s</sub><sup>s</sup>pH, are curved downward only for the CuĀ(II) complexes of <b>1</b> and <b>2</b> in both solvents and the ZnĀ(II) complex of <b>1</b> in methanol. Despite differences in the metal-binding abilities
and p<i>K</i><sub>a</sub> values for formation of the active
form, there is a common reaction mechanism, with the active form being <b>1</b>:MĀ(II):(<sup><b>ā</b></sup>OR) and <b>2</b>:MĀ(II):(<sup><b>ā</b></sup>OR), where MĀ(II):(<sup><b>ā</b></sup>OR) is the metal-bound alkoxide. The acceleration
provided by the metal ion is substantial, being 10<sup>14</sup>ā10<sup>19</sup> relative to the <i>k</i><sub>2</sub><sup>ĀÆOMe</sup> value for the alkoxide-promoted
alcoholysis of the uncomplexed amide
Cu(II)-Promoted Methanolysis of <i>N</i>,<i>N</i>-Dipicolylacetamide. Multistep Activation by Decoupling of >NĢāCī»O Resonance via Cu(II)āN Binding, Delivery of the Cu(II):(<sup>ā</sup>OCH<sub>3</sub>) Nucleophile, and Metal Ion Assistance of the Departure of the Leaving Group
The methanolysis of the CuĀ(II) complex of <i>N</i>-acetyl-<i>N</i>,<i>N</i>-bisĀ(2-picolyl)Āamine
(<b>2</b>) was investigated by a kinetic study as a function
of pH in methanol
at 25 Ā°C and computationally by DFT calculations. The active
species is the basic form of the complex (<b>3</b><sup>ā</sup>), or (<b>1</b>:CuĀ(II))Ā(<sup>ā</sup>OCH<sub>3</sub>)Ā(HOCH<sub>3</sub>)), and the rate constant
for its solvolysis is <i>k</i><sup>max</sup> = 1.5 Ć
10<sup>ā4</sup> s<sup>ā1</sup>. The mechanism involves
CuĀ(II) binding to the amide N lone pair, decoupling it from >NāCī»O
resonance, concomitant with CuĀ(II):(<sup>ā</sup>OCH<sub>3</sub>) delivery to the adjacent >NāCī»O unit, followed
by
CuĀ(II)-assisted departure of the <i>N</i>,<i>N</i>-bisĀ(2-picolyl)Āamide from a tetrahedral intermediate
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