8 research outputs found
Solvation and Proton-Coupled Electron Transfer Reduction Potential of <sup>2</sup>NO<sup>ā¢</sup> to <sup>1</sup>HNO in Aqueous Solution: A Theoretical Investigation
In
this work, quantum mechanical calculations and Monte Carlo statistical
mechanical simulations were carried out to investigate the solvation
properties of HNO in aqueous solution and to evaluate the proton-coupled
one electron reduction potential of <sup>2</sup>NO to <sup>1</sup>HNO, which is essential missing information to understand the fate
of <sup>2</sup>NO in the biological medium. Our results showed that
the <sup>1</sup>HNO molecule acts mainly as a hydrogen bond donor
in aqueous solution with an average energy of ā5.5 Ā± 1.3
kcal/mol. The solvation free energy of <sup>1</sup>HNO in aqueous
solution, computed using three approaches based on the linear response
theory, revealed that the current prediction of the hydration free
energy of HNO is, at least, 2 times underestimated. We proposed two
pathways for the production of HNO through reduction of NO. The first
pathway is the direct reduction of NO through proton-coupled electron
transfer to produce HNO, and the second path is the reduction of the
radical anion HONO<sup>ā¢ā</sup>, which is involved in
equilibrium with NO in aqueous solution. We have shown that both pathways
are viable processes under physiological conditions, having reduction
potentials of <i>E</i>Ā°ā² = ā0.161 V and <i>E</i>Ā°ā² ā 1 V for the first and second pathways,
respectively. The results shows that both processes can be promoted
by well-known biological reductants such as NADH, ascorbate, vitamin
E (tocopherol), cysteine, and glutathione, for which the reduction
potential at physiological pH is around ā0.3 to ā0.5
V. The computed reduction potential of NO through the radical anion
HONO<sup>ā¢ā</sup> can also explain the recent experimental
findings on the formation of HNO through the reduction of NO, promoted
by H<sub>2</sub>S, vitamin C, and aromatic alcohols. Therefore, these
results contribute to shed some light into the question of whether
and how HNO is produced in vivo and also for the understanding of
the biochemical and physiological effects of NO
[Ag(L)NO<sub>3</sub>] Complexes with 2āBenzoylpyridine-Derived Hydrazones: Cytotoxic Activity and Interaction with Biomolecules
Complexes [AgĀ(H2BzPh)ĀNO<sub>3</sub>] (<b>1</b>), [AgĀ(H2Bz<i>p</i>CH<sub>3</sub>Ph)ĀNO<sub>3</sub>] (<b>2</b>), [AgĀ(H2Bz<i>p</i>ClPh)ĀNO<sub>3</sub>] (<b>3</b>), and [AgĀ(H2Bz<i>p</i>NO<sub>2</sub>Ph)ĀNO<sub>3</sub>] (<b>4</b>) were
synthesized with 2-benzoylpyridine benzoylhydrazone (H2BzPh) and its <i>para</i>-methyl-benzoylhydrazone (H2Bz<i>p</i>CH<sub>3</sub>Ph), <i>para</i>-chloro-benzoylhydrazone (H2Bz<i>p</i>ClPh), and <i>para</i>-nitro-benzoylhydrazone
(H2Bz<i>p</i>NO<sub>2</sub>Ph) derivatives. Experimental
data indicate that the nitrate ligand binds more strongly to the silver
center through one of the oxygen atoms, whereas the second oxygen
atom from nitrate and the hydrazone oxygen makes much weaker interactions
with the metal. Dissociation of nitrate most probably occurs in solution
and in biological media. Interestingly, theoretical calculations suggested
that when dissociation of the nitrate takes place, all bond orders
involving the metal and the atoms from the hydrazone ligand increase
significantly, showing that the bonding of nitrate results in the
weakening of all other interactions in the metal coordination sphere.
Upon complexation of the hydrazones to silverĀ(I), cytotoxicity against
B16F10 metastatic murine melanoma cells increased in all cases. Complexes
(<b>1ā3</b>) proved to be more cytotoxic than cisplatin.
All compounds were more cytotoxic to B16F10 cells than to nontumorigenic
murine Melan-A melanocyte cells. Interestingly, the selectivity index
(SI = IC<sub>50Ā nonāmalignantĀ cells</sub>/IC<sub>50Ā tumorĀ cells</sub>) of complex (<b>1</b>), SI =
23, was much higher than that of the parent hydrazone ligand, SI =
9.5. Studies on the interactions of complexes (<b>1ā3</b>) with DNA suggested that although (<b>1ā3</b>) interact
with calf thymus DNA by an intercalative mode, direct covalent binding
of silverĀ(I) to DNA probably does not occur. Complexes (<b>1ā3</b>) interact in vitro with human serum albumin indicating that these
compounds could be transported by albumin
Water Solvent Effect on Theoretical Evaluation of <sup>1</sup>H NMR Chemical Shifts: <i>o</i>āMethyl-Inositol Isomer
In this paper, density
functional theory calculations of nuclear
magnetic resonance (NMR) chemical shifts for l-quebrachitol
isomer, previously studied in our group, are reported with the aim
of investigating in more detail the water solvent effect on the prediction
of <sup>1</sup>H NMR spectra. In order to include explicit water molecules,
20 water-l-quebrachitol configurations obtained from Monte
Carlo simulation were selected to perform geometry optimizations using
the effective fragment potential method encompassing 60 water molecules
around the solute. The solvated solute optimized geometries were then
used in B3LYP/6-311+GĀ(2d,p) NMR calculations with PCM-water. The inclusion
of explicit solvent in the B3LYP NMR calculations resulted in large
changes in the <sup>1</sup>H NMR profiles. We found a remarkable improvement
in the agreement with experimental NMR profiles when the explicit
hydrated l-quebrachitol structure is used in B3LYP <sup>1</sup>H NMR calculations, yielding a mean absolute error (MAE) of only
0.07 ppm, much lower than reported previously for the gas phase optimized
structure (MAE = 0.11 ppm). In addition, a very improved match between
theoretical and experimental <sup>1</sup>H NMR spectrum measured in
D<sub>2</sub>O was achieved with the new hydrated optimized l-quebrachitol structure, showing that a fine-tuning of the theoretical
NMR spectra can be accomplished once solvent effects are properly
considered
[Ag(L)NO<sub>3</sub>] Complexes with 2āBenzoylpyridine-Derived Hydrazones: Cytotoxic Activity and Interaction with Biomolecules
Complexes [AgĀ(H2BzPh)ĀNO<sub>3</sub>] (<b>1</b>), [AgĀ(H2Bz<i>p</i>CH<sub>3</sub>Ph)ĀNO<sub>3</sub>] (<b>2</b>), [AgĀ(H2Bz<i>p</i>ClPh)ĀNO<sub>3</sub>] (<b>3</b>), and [AgĀ(H2Bz<i>p</i>NO<sub>2</sub>Ph)ĀNO<sub>3</sub>] (<b>4</b>) were
synthesized with 2-benzoylpyridine benzoylhydrazone (H2BzPh) and its <i>para</i>-methyl-benzoylhydrazone (H2Bz<i>p</i>CH<sub>3</sub>Ph), <i>para</i>-chloro-benzoylhydrazone (H2Bz<i>p</i>ClPh), and <i>para</i>-nitro-benzoylhydrazone
(H2Bz<i>p</i>NO<sub>2</sub>Ph) derivatives. Experimental
data indicate that the nitrate ligand binds more strongly to the silver
center through one of the oxygen atoms, whereas the second oxygen
atom from nitrate and the hydrazone oxygen makes much weaker interactions
with the metal. Dissociation of nitrate most probably occurs in solution
and in biological media. Interestingly, theoretical calculations suggested
that when dissociation of the nitrate takes place, all bond orders
involving the metal and the atoms from the hydrazone ligand increase
significantly, showing that the bonding of nitrate results in the
weakening of all other interactions in the metal coordination sphere.
Upon complexation of the hydrazones to silverĀ(I), cytotoxicity against
B16F10 metastatic murine melanoma cells increased in all cases. Complexes
(<b>1ā3</b>) proved to be more cytotoxic than cisplatin.
All compounds were more cytotoxic to B16F10 cells than to nontumorigenic
murine Melan-A melanocyte cells. Interestingly, the selectivity index
(SI = IC<sub>50Ā nonāmalignantĀ cells</sub>/IC<sub>50Ā tumorĀ cells</sub>) of complex (<b>1</b>), SI =
23, was much higher than that of the parent hydrazone ligand, SI =
9.5. Studies on the interactions of complexes (<b>1ā3</b>) with DNA suggested that although (<b>1ā3</b>) interact
with calf thymus DNA by an intercalative mode, direct covalent binding
of silverĀ(I) to DNA probably does not occur. Complexes (<b>1ā3</b>) interact in vitro with human serum albumin indicating that these
compounds could be transported by albumin
[Ag(L)NO<sub>3</sub>] Complexes with 2āBenzoylpyridine-Derived Hydrazones: Cytotoxic Activity and Interaction with Biomolecules
Complexes [AgĀ(H2BzPh)ĀNO<sub>3</sub>] (<b>1</b>), [AgĀ(H2Bz<i>p</i>CH<sub>3</sub>Ph)ĀNO<sub>3</sub>] (<b>2</b>), [AgĀ(H2Bz<i>p</i>ClPh)ĀNO<sub>3</sub>] (<b>3</b>), and [AgĀ(H2Bz<i>p</i>NO<sub>2</sub>Ph)ĀNO<sub>3</sub>] (<b>4</b>) were
synthesized with 2-benzoylpyridine benzoylhydrazone (H2BzPh) and its <i>para</i>-methyl-benzoylhydrazone (H2Bz<i>p</i>CH<sub>3</sub>Ph), <i>para</i>-chloro-benzoylhydrazone (H2Bz<i>p</i>ClPh), and <i>para</i>-nitro-benzoylhydrazone
(H2Bz<i>p</i>NO<sub>2</sub>Ph) derivatives. Experimental
data indicate that the nitrate ligand binds more strongly to the silver
center through one of the oxygen atoms, whereas the second oxygen
atom from nitrate and the hydrazone oxygen makes much weaker interactions
with the metal. Dissociation of nitrate most probably occurs in solution
and in biological media. Interestingly, theoretical calculations suggested
that when dissociation of the nitrate takes place, all bond orders
involving the metal and the atoms from the hydrazone ligand increase
significantly, showing that the bonding of nitrate results in the
weakening of all other interactions in the metal coordination sphere.
Upon complexation of the hydrazones to silverĀ(I), cytotoxicity against
B16F10 metastatic murine melanoma cells increased in all cases. Complexes
(<b>1ā3</b>) proved to be more cytotoxic than cisplatin.
All compounds were more cytotoxic to B16F10 cells than to nontumorigenic
murine Melan-A melanocyte cells. Interestingly, the selectivity index
(SI = IC<sub>50Ā nonāmalignantĀ cells</sub>/IC<sub>50Ā tumorĀ cells</sub>) of complex (<b>1</b>), SI =
23, was much higher than that of the parent hydrazone ligand, SI =
9.5. Studies on the interactions of complexes (<b>1ā3</b>) with DNA suggested that although (<b>1ā3</b>) interact
with calf thymus DNA by an intercalative mode, direct covalent binding
of silverĀ(I) to DNA probably does not occur. Complexes (<b>1ā3</b>) interact in vitro with human serum albumin indicating that these
compounds could be transported by albumin
Synthesis, Magnetostructural Correlation, and Catalytic Promiscuity of Unsymmetric Dinuclear Copper(II) Complexes: Models for Catechol Oxidases and Hydrolases
Herein, we report the synthesis and characterization,
through elemental
analysis, electronic spectroscopy, electrochemistry, potentiometric
titration, electron paramagnetic resonance, and magnetochemistry,
of two dinuclear copperĀ(II) complexes, using the unsymmetrical ligands <i>N</i>ā²,<i>N</i>ā²,<i>N</i>-trisĀ(2-pyridylmethyl)-<i>N</i>-(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol
(<b>L1</b>) and <i>N</i>ā²,<i>N</i>ā²-bisĀ(2-pyridylmethyl)-<i>N</i>,<i>N</i>-(2-hydroxybenzyl)Ā(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol
(<b>L2</b>). The structures of the complexes [Cu<sub>2</sub>(<b>L1</b>)Ā(Ī¼-OAc)]Ā(ClO<sub>4</sub>)<sub>2</sub>Ā·(CH<sub>3</sub>)<sub>2</sub>CHOH (<b>1</b>) and [Cu<sub>2</sub>(<b>L2</b>)Ā(Ī¼-OAc)]Ā(ClO<sub>4</sub>)Ā·H<sub>2</sub>OĀ·(CH<sub>3</sub>)<sub>2</sub>CHOH (<b>2</b>) were determined by X-ray
crystallography. The complex [Cu<sub>2</sub>(<b>L3</b>)Ā(Ī¼-OAc)]<sup>2+</sup> [<b>3</b>; <b>L3</b> = <i>N</i>-(2-hydroxybenzyl)-<i>N</i>ā²,<i>N</i>ā²,<i>N</i>-trisĀ(2-pyridylmethyl)-1,3-propanediamin-2-ol]
was included in this study for comparison purposes only (Neves et
al. <i>Inorg. Chim. Acta</i> <b>2005</b>, <i>358</i>, 1807ā1822). Magnetic data show that the Cu<sup>II</sup> centers in <b>1</b> and <b>2</b> are antiferromagnetically
coupled and that the difference in the exchange coupling <i>J</i> found for these complexes (<i>J</i> = ā4.3 cm<sup>ā1</sup> for <b>1</b> and <i>J</i> = ā40.0
cm<sup>ā1</sup> for <b>2</b>) is a function of the CuāOāCu
bridging angle. In addition, <b>1</b> and <b>2</b> were
tested as catalysts in the oxidation of the model substrate 3,5-di-<i>tert</i>-butylcatechol and can be considered as functional models
for catechol oxidase. Because these complexes possess labile sites
in their structures and in solution they have a potential nucleophile
constituted by a terminal Cu<sup>II</sup>-bound hydroxo group, their
activity toward hydrolysis of the model substrate 2,4-bisĀ(dinitrophenyl)Āphosphate
and DNA was also investigated. Double electrophilic activation of
the phosphodiester by monodentate coordination to the Cu<sup>II</sup> center that contains the phenol group with <i>tert</i>-butyl substituents and hydrogen bonding of the protonated phenol
with the phosphate O atom are proposed to increase the hydrolase activity
(<i>K</i><sub>ass.</sub> and <i>k</i><sub>cat.</sub>) of <b>1</b> and <b>2</b> in comparison with that found
for complex <b>3</b>. In fact, complexes <b>1</b> and <b>2</b> show both oxidoreductase and hydrolase/nuclease activities
and can thus be regarded as man-made models for studying catalytic
promiscuity
Synthesis, Magnetostructural Correlation, and Catalytic Promiscuity of Unsymmetric Dinuclear Copper(II) Complexes: Models for Catechol Oxidases and Hydrolases
Herein, we report the synthesis and characterization,
through elemental
analysis, electronic spectroscopy, electrochemistry, potentiometric
titration, electron paramagnetic resonance, and magnetochemistry,
of two dinuclear copperĀ(II) complexes, using the unsymmetrical ligands <i>N</i>ā²,<i>N</i>ā²,<i>N</i>-trisĀ(2-pyridylmethyl)-<i>N</i>-(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol
(<b>L1</b>) and <i>N</i>ā²,<i>N</i>ā²-bisĀ(2-pyridylmethyl)-<i>N</i>,<i>N</i>-(2-hydroxybenzyl)Ā(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol
(<b>L2</b>). The structures of the complexes [Cu<sub>2</sub>(<b>L1</b>)Ā(Ī¼-OAc)]Ā(ClO<sub>4</sub>)<sub>2</sub>Ā·(CH<sub>3</sub>)<sub>2</sub>CHOH (<b>1</b>) and [Cu<sub>2</sub>(<b>L2</b>)Ā(Ī¼-OAc)]Ā(ClO<sub>4</sub>)Ā·H<sub>2</sub>OĀ·(CH<sub>3</sub>)<sub>2</sub>CHOH (<b>2</b>) were determined by X-ray
crystallography. The complex [Cu<sub>2</sub>(<b>L3</b>)Ā(Ī¼-OAc)]<sup>2+</sup> [<b>3</b>; <b>L3</b> = <i>N</i>-(2-hydroxybenzyl)-<i>N</i>ā²,<i>N</i>ā²,<i>N</i>-trisĀ(2-pyridylmethyl)-1,3-propanediamin-2-ol]
was included in this study for comparison purposes only (Neves et
al. <i>Inorg. Chim. Acta</i> <b>2005</b>, <i>358</i>, 1807ā1822). Magnetic data show that the Cu<sup>II</sup> centers in <b>1</b> and <b>2</b> are antiferromagnetically
coupled and that the difference in the exchange coupling <i>J</i> found for these complexes (<i>J</i> = ā4.3 cm<sup>ā1</sup> for <b>1</b> and <i>J</i> = ā40.0
cm<sup>ā1</sup> for <b>2</b>) is a function of the CuāOāCu
bridging angle. In addition, <b>1</b> and <b>2</b> were
tested as catalysts in the oxidation of the model substrate 3,5-di-<i>tert</i>-butylcatechol and can be considered as functional models
for catechol oxidase. Because these complexes possess labile sites
in their structures and in solution they have a potential nucleophile
constituted by a terminal Cu<sup>II</sup>-bound hydroxo group, their
activity toward hydrolysis of the model substrate 2,4-bisĀ(dinitrophenyl)Āphosphate
and DNA was also investigated. Double electrophilic activation of
the phosphodiester by monodentate coordination to the Cu<sup>II</sup> center that contains the phenol group with <i>tert</i>-butyl substituents and hydrogen bonding of the protonated phenol
with the phosphate O atom are proposed to increase the hydrolase activity
(<i>K</i><sub>ass.</sub> and <i>k</i><sub>cat.</sub>) of <b>1</b> and <b>2</b> in comparison with that found
for complex <b>3</b>. In fact, complexes <b>1</b> and <b>2</b> show both oxidoreductase and hydrolase/nuclease activities
and can thus be regarded as man-made models for studying catalytic
promiscuity
Synthesis, Magnetostructural Correlation, and Catalytic Promiscuity of Unsymmetric Dinuclear Copper(II) Complexes: Models for Catechol Oxidases and Hydrolases
Herein, we report the synthesis and characterization,
through elemental
analysis, electronic spectroscopy, electrochemistry, potentiometric
titration, electron paramagnetic resonance, and magnetochemistry,
of two dinuclear copperĀ(II) complexes, using the unsymmetrical ligands <i>N</i>ā²,<i>N</i>ā²,<i>N</i>-trisĀ(2-pyridylmethyl)-<i>N</i>-(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol
(<b>L1</b>) and <i>N</i>ā²,<i>N</i>ā²-bisĀ(2-pyridylmethyl)-<i>N</i>,<i>N</i>-(2-hydroxybenzyl)Ā(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol
(<b>L2</b>). The structures of the complexes [Cu<sub>2</sub>(<b>L1</b>)Ā(Ī¼-OAc)]Ā(ClO<sub>4</sub>)<sub>2</sub>Ā·(CH<sub>3</sub>)<sub>2</sub>CHOH (<b>1</b>) and [Cu<sub>2</sub>(<b>L2</b>)Ā(Ī¼-OAc)]Ā(ClO<sub>4</sub>)Ā·H<sub>2</sub>OĀ·(CH<sub>3</sub>)<sub>2</sub>CHOH (<b>2</b>) were determined by X-ray
crystallography. The complex [Cu<sub>2</sub>(<b>L3</b>)Ā(Ī¼-OAc)]<sup>2+</sup> [<b>3</b>; <b>L3</b> = <i>N</i>-(2-hydroxybenzyl)-<i>N</i>ā²,<i>N</i>ā²,<i>N</i>-trisĀ(2-pyridylmethyl)-1,3-propanediamin-2-ol]
was included in this study for comparison purposes only (Neves et
al. <i>Inorg. Chim. Acta</i> <b>2005</b>, <i>358</i>, 1807ā1822). Magnetic data show that the Cu<sup>II</sup> centers in <b>1</b> and <b>2</b> are antiferromagnetically
coupled and that the difference in the exchange coupling <i>J</i> found for these complexes (<i>J</i> = ā4.3 cm<sup>ā1</sup> for <b>1</b> and <i>J</i> = ā40.0
cm<sup>ā1</sup> for <b>2</b>) is a function of the CuāOāCu
bridging angle. In addition, <b>1</b> and <b>2</b> were
tested as catalysts in the oxidation of the model substrate 3,5-di-<i>tert</i>-butylcatechol and can be considered as functional models
for catechol oxidase. Because these complexes possess labile sites
in their structures and in solution they have a potential nucleophile
constituted by a terminal Cu<sup>II</sup>-bound hydroxo group, their
activity toward hydrolysis of the model substrate 2,4-bisĀ(dinitrophenyl)Āphosphate
and DNA was also investigated. Double electrophilic activation of
the phosphodiester by monodentate coordination to the Cu<sup>II</sup> center that contains the phenol group with <i>tert</i>-butyl substituents and hydrogen bonding of the protonated phenol
with the phosphate O atom are proposed to increase the hydrolase activity
(<i>K</i><sub>ass.</sub> and <i>k</i><sub>cat.</sub>) of <b>1</b> and <b>2</b> in comparison with that found
for complex <b>3</b>. In fact, complexes <b>1</b> and <b>2</b> show both oxidoreductase and hydrolase/nuclease activities
and can thus be regarded as man-made models for studying catalytic
promiscuity