Download A comparison of copper(I) and silver(I) complexes of glycine

A comparison of copper(I) and silver(I) complexes of glycine,
diglycine and triglycine
Tamer Shoeib, Christopher F. Rodriquez, K. W. Michael Siu and Alan C. Hopkinson*
Department of Chemistry and Center for Research in Mass Spectrometry, Y ork University,
4700 Keele Street, T oronto, Ontario, Canada M3J 1P3. E-mail : ach=yorku.ca
Received 2nd November 2000, Accepted 8th January 2001
First published as an Advance Article on the web 7th February 2001
Density functional calculations at B3LYP/DZVP were used to obtain structural information, relative free
energies of di†erent isomers and binding energies for the following reaction in the gas phase : M`
] (glycyl) glycine ] MÈ(glycyl) glycine`, where M \ Ag or Cu and n \ 0È2. For the complexes with Cu`,
n
n
optimizations were also performed at B3LYP/6È31&&G(d,p) and single-point calculations at
MP2(fc)/6È311&&G(2df,2p)//B3LYP/DZVP. The calculated binding energies for the Cu` complexes are all
higher than those of the structurally similar Ag` ions. These calculated binding energy di†erences become
larger as the size of the ligand increases. For all the Cu` complexes examined, the coordination number of the
copper ion does not exceed two, whereas for the silver complexes tri- and tetracoordinate Ag` structures are
calculated to be at low energy minima. SigniÐcant structural and relative free energy di†erences occur between
the lowest energy “ zwitterionic Ï forms of the MÈ(glycyl) glycine` complexes.
n
Introduction
The area of gas-phase transition metal ion chemistry has experienced explosive growth in the recent past.1 This has been
stimulated by the importance of transition metal ions in a
wide variety of Ðelds, including catalysis, organometallic reactions and especially biochemistry, where metal ions can be
very inÑuential in determining the three-dimensional structures of nucleic acids.2h5 For many proteins, a variety of metal
ions are required to interact with the appropriate peptides or
proteins in order for the latter to be able to carry out their
regulatory or structural functions.6 It is therefore imperative
that we further our understanding of the interactions of these
metal ions with molecules of biological importance.
Alkali metal cations, for example, are essential for maintaining osmotic equilibrium in cells ; they also play a role in
the transport of amino acids through their binding to some
proteins.7h9 Transition metal ions, such as Cu(I), also play
very important roles in biological processes such as oxidation,
dioxygen transport and electron transfer.7,10 Silver(I) compounds, on the other hand, are used as potent antibacterial
agents.11 Excluding those of mercury, silver compounds are
among the most toxic towards bacteria and other microorganisms. This fact is exploited by the use of silver(I) compounds for medicinal purposes ; silver nitrate has been used to
combat infantile blindness12 and silver sulfadiazine is commonly found in creams used to treat severe burns and infectious skin diseases.13,14 The role of silver sulfadiazine has
been examined and the general agreement is that the action of
the drug is due to its ability to release silver ions which are the
active species.14 Silver(I) diphosphine complexes have been
shown to be potently cytotoxic to cancerous melanoma
cells,15 while other silver-containing compounds have been
e†ectively used for treatment of ulcers.16
Metal ions can bind to a variety of sites on a peptide,
including the amino nitrogen at the N-terminus, the carboxylate anion at the C-terminus, the carbonyl oxygen atoms
along the backbone and the side chains of the glutamine and
DOI : 10.1039/b008836f
asparagine residues, and the nitrogen atoms on the side chains
of basic residues such as lysine, arginine and histidine. Other
possible sites of metal ion attachment to peptides include the
hydroxyl oxygen atoms on the side chains of serine, threonine
and tyrosine residues and the sulfur atoms on the side chains
of methionine and cysteine residues. The fact that a variety of
metal ions can easily bind to peptides has been exploited in
the Ðeld of mass spectrometry, where metal ions such as Li`,
Na`, Cu` and Ag` have been used as ionizing agents for
peptide sequencing.17h19 Exploring the nature of these metal
ionÈpeptide interactions will not only provide information on
their binding energies to a class of biologically important molecules, but will also be extremely useful in the interpretation of
the mass spectra of such complexes obtained either under
metastable or via collision-induced dissociation conditions.
The coordination modes of metal ions greatly inÑuence
their binding energies and to some extent their site of attachment to a ligand. Some metals have a strong preference for a
particular coordination mode, while others can adopt di†erent
coordination geometries. These coordination preferences
could play a signiÐcant role in the biological functions of
metal-containing enzymes. The metal-speciÐc binding sites of
some proteins achieve their selectivity by providing a coordination environment preferred by only one metal ion naturally
found in living systems. As a consequence, some metals that
are not naturally found in living systems owe their toxicity to
their ability to coordinate strongly and compete e†ectively for
the binding sites of biologically important metal ions.
Modeling ionÈprotein complexes is a difficult task that
requires accurate knowledge of the interactions of these ions
with amino acids and small peptides. Recently, the kinetic
method has been used to obtain ladders of relative Cu` and
Ag` affinities of almost all essential a-amino acids.20,21 Theoretical studies have also probed the interactions of Cu` with
glycine, cysteine and serine 22,23 and those of Ag` with all 20
a-amino acids.24 While these studies provide values of the
binding energies and some insight into the coordination preferences of these two isoelectronic transition metal ions, no
Phys. Chem. Chem. Phys., 2001, 3, 853È861
This journal is ( The Owner Societies 2001
853
direct comparisons between their interactions with amino
acids or peptides have previously been made. This work provides a step towards this goal by means of a comprehensive
description of the interaction of Cu` and Ag` with each of
glycine (G), glycylglycine (GG) and glycylglycylglycine (GGG).
Glycine was chosen as several groups have studied its interaction with metal ions, including Cu`, and its binding energy
to that ion is well established.22,23 For reasons of computational tractability, the largest peptide that is being examined is
triglycine, the smallest peptide unit that reasonably models
binding present in some larger peptides.
Methods
The most reliable theoretical value in the literature for the
Cu` affinity of glycine was obtained by the CCSD(T) method
with a very large basis set.23 Unfortunately, this level of
theory is computationally prohibitive for calculations on peptides such as GG and GGG. The procedure used here was to
perform structure optimization calculations using hybrid
density functional theory at the B3LYP level25h27 using the
DZVP basis set28 and to follow these by single-point calculations at MP2(fc)/6È311&&G(2df,2p).29h36 The latter level of
theory has been shown to reproduce satisfactorily the Cu`
binding energy of glycine as calculated by the CCSD(T)
method.23 As an independent check on the geometries and
energetics provided by this procedure, we also optimized three
conformers of GGG and the three lowest isomers of
GGGÈCu` at B3LYP/6È31&&G(d,p).37,38 In every comparison, we found no substantive di†erences in the structures and
relative energies provided by the two di†erent basis sets.
Ag` affinities were calculated at B3LYP/DZVP. This
approach has been shown to provide excellent agreement with
experimental values for systems similar to those under study
here.39,40 All calculations were performed using the GAUSSIAN 98 program.41 All geometry optimizations were performed without any symmetry constraints and all optimized
structures were characterized by harmonic frequency calculations and shown to be at minima.
Results and discussion
Structural details and relative free energies
Glycine. Neutrals. The structure of neutral and metal ion
containing glycine in the gas phase has been the subject of
several extensive investigations.42h44 Only the three lowest
energy conformers as previously determined were investigated
here. These structures are shown in Fig. 1. Total energies,
zero-point vibrational terms, thermal corrections, entropies
and their relative free energies are given in Table 1.
GlycineÈAg`. All attempts to optimize a tricoordinate Ag`
structure by allowing for interactions of the metal ion with the
nitrogen and each of the oxygen atoms of glycine eventually
resulted in 1Ag, the lowest energy structure found (Fig. 1). 2Ag
is the lowest energy structure of the “ zwitterionic ÏÏ form, the
structure in which Ag` is added to the zwitterion of glycine.
This is only 4.5 kcal mol~1 higher in free energy than 1Ag (see
Table 1).
GlycineÈCu`. Here, just as others have reported,22 attempts
to produce a tricoordinate glycineÈCu` structure were not
successful. The structural parameters for the lowest energy
structure found for this complex, 1Cu, are shown in Fig. 1. Ion
1Cu is dicoordinate, with the two most basic sites of glycine,
the terminal amino group and the carbonyl oxygen, interacting with Cu`. This structure is similar to that of 1Ag on
the glycineÈAg` surface, although the metalÈligand distances
Fig. 1 Structures of glycine and AgÈglycine` and CuÈglycine` complexes as optimized at B3LYP/DZVP. Upper numbers are for M \ Ag and
lower italicized numbers are for M \ Cu. Bond lengths are in a- ngstroŽms and angles are in degrees.
854
Phys. Chem. Chem. Phys., 2001, 3, 853È861
Table 1 Total electronic energies, unscaled zero-point energies (ZPE), enthalpy corrections, entropies and relative free energies. Upper numbers
are calculated at B3LYP/DZVP and lower bold face numbers are calculated at MP2(fc)/6È311&&G(2df,2p)//B3LYP/DZVP
Structure
1N
2N
3N
Ag`
1Ag
2Ag
Cu`
1Cu
2Cu
Electronic
energy/hartree
ZPE/
kcal mol~1
H¡ [ H¡/
298mol~1
0
kcal
Entropy/
cal mol~1 K~1
Relative free energy
at 298 K/kcal mol~1
[284.477 42
Ô283.938 99
[284.475 10
Ô283.936 39
[284.476 33
Ô283.938 23
[5199.198 15
[5483.759 22
[5483.751 50
[1639.887 04
Ô1639.050 19
[1924.491 38
Ô1923.102 27
[1924.475 86
Ô1923.086 80
50.1
4.1
75.2
50.2
4.1
76.0
50.5
3.9
73.4
0.0
0.0
1.3
1.9
1.4
4.0
51.8
51.8
1.5
5.0
5.2
1.5
39.9
86.5
88.3
38.4
52.1
4.9
84.2
52.1
5.1
86.9
are shorter in the glycineÈCu` complex. This is simply a
reÑection of the smaller ionic radius of Cu`.
Structure 2Cu is the lowest energy conformer of the zwitterionic form of the complex ; it lies 9.2 kcal mol~1 higher in free
energy than 1Cu. This relative free energy di†erence is more
than double the free energy di†erence of the equivalent
glycineÈAg` structures. This could be explained by considering the fact that, unlike Ag` in structure 2Ag, Cu` in structure 2Cu coordinates only with one of the oxygen atoms of the
CO ~ group. This unsymmetrical coordination of the lowest
2
energy zwitterionic form of the glycineÈCu` complex was previously reported22,23 and was attributed to the strong local
dipoles on the NÈH bonds that lead to a global dipole
moment pointing towards the opposite oxygen.22 However, it
has been pointed out that the analogous M`ÈCO ~ coordi2
nation with alkali metal cations (e.g., Li`, Na`, K`, Rb` and
Cs`) all show dicoordination despite similar dipole moment
e†ects.23,44 An alternative explanation is that the unsymmetrical interactions of Cu` to the CO ~ group of the zwitterionic
2
form of glycine provide a way of minimizing the repulsion
between the occupied d shell of the metal and the lone pairs of
oxygens.23 This argument, however, is also unsatisfactory as
Ag` is isoelectronic with Cu` and yet prefers symmetrical
coordination with the CO ~ group of the zwitterionic form of
2
glycine. In both cases, however, the presence of the metal ion
strongly stabilizes the zwitterionic form of glycine ; on the
potential energy hypersurface for glycine the zwitterion is not
even at a minimum.45
Glycylglycine. Neutrals. Conformational searches using
molecular mechanics techniques were used to investigate
rapidly the potential energy surface of neutral GG. The lowlying conformers obtained from this search were then optimized at B3LYP/DZVP, followed by single-point calculations
at MP2(fc)/6È311&&G(2df,2p) (see Fig. 2 and Table 2). The
three lowest energy structures obtained for this surface are
shown in Fig. 2. Two of these three structures, 4N and 5N,
have folded conformations. Recently, Cerda et al.46 reported
structure 4N to be the lowest energy conformer on this
surface ; however, in their work structure 5N was not considered. As shown in Fig. 2, structure 5N, displaying two
internal hydrogen bonds, appears to be the most compact of
the three conformers. These three conformers have almost
identical free energies, and therefore it is important to clarify
that for our discussion of signiÐcant structural and relative
free energy di†erences of complexes of Cu` and Ag` with
0.0
4.5
0.0
0.0
9.2
9.2
polyglycines and also for providing good estimates of the
binding energies of these two metal ions, it is not crucial that
the global minimum of the neutral peptide be identiÐed.
GlycylglycineÈAg`. Previously we have shown 47 that the
““ external ÏÏ proton in protonated triglycine is ““ mobile ÏÏ. In
that study47 we demonstrated that the barriers involved for
the ““ external ÏÏ proton to migrate from the terminal nitrogen
to any of the carbonyl oxygen atoms along the peptide backbone are relatively low. In a subsequent study, we also showed
that these barriers are signiÐcantly lowered by the addition of
a single solvent molecule.48 Based on this knowledge, we did
not limit ourselves in this study to structures where the proton
is on the terminal amino group. The potential energy surface
of the GGÈAg` complex was rigorously examined. Eleven
structures on this surface were optimized and characterized as
being at minima. The lowest energy structure, 3Ag, found on
this surface is shown in Fig. 2. This structure is very similar to
the lowest energy structure of the glycineÈAg` complex, ion
1Ag, where the silver ion is dicoordinate, attached to the terminal nitrogen and the carbonyl oxygen of the amide. Structure 4Ag, depicts the only tricoordinate silver complex of GG
found on this surface ; here the silver ion is chelated to the
terminal nitrogen and to both of the carbonyl oxygens of GG.
Interaction of Ag` with the three most electron-rich sites of
GG might a priori be expected to lead to the lowest energy
structure ; however, the steric e†ect of folding the GG backbone to accommodate this mode of coordination makes this
structure less favored, but still competitive at a relative free
energy of only 1.2 kcal mol~1 higher than the structure at the
global minimum. Ion 5Ag, where Ag` binds to both carbonyl
oxygen atoms, is further stabilized by a hydrogen bond in
which the lone pair on the terminal amino interacts with an
amide hydrogen that has been rendered more acidic by complexation of the oxygen on the same amide linkage with Ag`.
This ion is found to be at a low-lying energy minimum, being
only 2.5 kcal mol~1 above the global minimum.
Permitting the silver ion to bind with both the terminal
amino nitrogen and the terminal carbonyl oxygen results in
isomer 6Ag, a structure that is 6.6 kcal mol~1 higher in energy
than 3Ag.
The zwitterionic forms of the GGÈAg` complex were also
extensively investigated. The three lowest energy conformers
of this form of the ion are shown in Fig. 2. The lowest energy
structure of all the zwitterions on this surface, structure 7Ag,
is only 8 kcal mol~1 above structure 3Ag. This zwitterionic
structure is stabilized by two internal hydrogen bonds. One of
these bonds is between the terminal amino nitrogen and the
acidic amide hydrogen ; the second, and signiÐcantly stronger
Phys. Chem. Chem. Phys., 2001, 3, 853È861
855
Fig. 2 Structures of diglycine and AgÈdiglycine` and CuÈdiglycine` complexes as optimized at B3LYP/DZVP. Upper numbers are for M \ Ag
and lower italicized numbers are for M \ Cu. Bond lengths are in a- ngstroŽms and angles are in degrees.
interaction, is between the hydroxy hydrogen and the carbonyl oxygen of the CO ~ group. The latter interaction is by far
2
the shortest hydrogen bond found on this potential hypersurface. The position of the hydrogen atom between two very
electronegative sites, the relatively short distance between that
hydrogen and the carbonyl oxygen of the CO ~ group (1.399
2
856
Phys. Chem. Chem. Phys., 2001, 3, 853È861
AŽ ) and the OÈHÈO angle of 174¡, which is nearly the ideal
180¡, are all factors that contribute to the strength of this
hydrogen bond and hence to the stability of this structure.
The other two zwitterionic structures presented here, 8Ag and
9Ag, both involve the localization of some of the positive
charge on the terminal nitrogen ; this arrangement leads to
Table 2 Total electronic energies, unscaled zero-point energies (ZPE), thermal energies, entropies and relative free energies. Upper numbers are
calculated at B3LYP/DZVP, central italicized numbers are calculated at B3LYP/6È31&&G(d,p) and lower bold face numbers are calculated at
MP2(fc)/6È311&&G(2df,2p)//B3LYP/DZVP
Structure
4N
5N
6N
3Ag
4Ag
5Ag
6Ag
7Ag
8Ag
9Ag
3Cu
5Cu
6Cu
7Cu
8Cu
9Cu
Electronic
energy/
hartree
[492.518 12
Ô491.572 24
[492.519 88
Ô491.575 51
[492.516 19
Ô491.570 98
[5691.814 03
[5691.811 73
[5691.808 48
[5691.803 59
[5691.801 24
[5691.795 27
[5691.793 79
[2132.549 45
[2132.637 91
Ô2130.752 37
[2132.545 94
[2132.634 36
Ô2130.747 07
[2132.550 17
[2132.636 80
Ô2130.753 68
[2132.525 74
Ô2130.728 21
[2132.523 11
Ô2130.726 23
[2132.521 26
Ô2130.724 12
ZPE/
kcal mol~1
H¡ [ H¡/
298
0
kcal mol~1
Entropy/
cal mol~1 K~1
85.4
6.7
100.7
85.8
6.5
95.6
85.0
6.9
100.5
86.9
86.7
86.4
87.0
85.4
87.6
86.7
87.3
87.1
7.7
7.7
7.9
7.1
7.7
7.5
7.8
7.5
6.9
109.8
109.2
111.3
109.9
111.3
108.3
111.7
107.4
106.5
86.9
86.8
7.5
6.9
105.5
105.1
87.8
87.7
7.2
6.6
103.1
102.3
86.0
7.6
109.5
88.1
7.3
105.3
86.9
7.7
109.3
some charge separation, as the metal center and the terminal
NH ` group account for most of the positive charge in these
3
species.
GlycylglycineÈCu`. All attempts to form tricoordinate
structures of Cu` failed. Structure 3Cu, where Cu` is chelated
to the terminal amino group and the carbonyl oxygen of the
amide, is at the global minimum structure on this surface.
However, in contrast to the GGÈAg` potential energy surface,
structure 6Cu, in which the two terminal groups chelate Cu`,
is almost degenerate with the global minimum. As on the
GGÈAg` surface, structure 5, where the Cu` coordinates with
both of the carbonyl oxygens of GG, is a relatively low energy
species, only 2.4 kcal mol~1 higher in free energy relative to
the global minimum.
The zwitterionic forms of the GGÈCu` complex display
remarkable di†erences from those of their Ag` counterparts,
both in structure and free energies relative to their respective
global minima. Cu` clearly displays its preference for monocoordination to only one of the oxygen atoms of the CO ~
2
group in structure 7Cu. The presence of the two intramolecular hydrogen bonds in this structure, similar to those in 7Ag,
the GGÈAg` counterpart of this structure, help to stabilize
this isomer. However, the preference of Cu` for monocoordination makes this structure a relatively high energy
species, 12.5 kcal mol~1 higher in free energy above 3Cu.
The preference of Cu` to be monocoordinate with the
CO ~ group of the zwitterionic form of GG is also shown in
2
structure 8Cu. Despite the stabilizing e†ect of the hydrogen
bond between the terminal ammonium group and the carbonyl of the C-terminus, this structure is not energetically favorable relative to others on this surface.
Structure 9Cu, the highest energy species of GGÈCu` considered in this work, is interesting as, unlike in 7Cu and 8Cu,
it has the Cu` dicoordinated with both oxygens of the CO ~
2
group in a nearly symmetrical fashion. This is perhaps due to
the absence of strong intramolecular hydrogen bonding interactions with either of these oxygens. Such interactions deplete
Relative free
energy at 298 K/
kcal mol~1
0.0
0.4
0.5
0.0
0.5
1.3
0.0
1.2
2.5
6.6
6.2
12.8
13.1
0.0
0.0
0.0
2.4
1.5
3.5
1.0
2.9
0.6
12.5
13.2
17.4
17.6
16.9
17.0
some of the electron density from the carbonyl oxygen where
the hydrogen bonding takes place, thereby rendering that carbonyl oxygen a less attractive binding site for the copper ion.
This seems to be a more satisfactory explanation of the
unsymmetrical coordination of Cu` to the CO ~ group of the
2
zwitterions encountered here and previously in the literature.22,23 Further evidence is obtained upon careful inspection of structure 9Cu. The weak hydrogen bond between the
mildly acidic amide hydrogen and the adjacent carbonyl
oxygen of the CO ~ group causes some depletion of some of
2
the electron density on that oxygen, thereby rendering it a less
attractive site for Cu` attachment, as reÑected in the longer
bond distance between that oxygen and the metal center
(2.185 AŽ ) relative to the of the metal center and the other carbonyl oxygen of the CO ~ group (2.067 AŽ ). This explanation
2
is further corroborated with the symmetrical coordination
observed in this work of Cu` to the carbonyl oxygens of the
CO ~ group of cuprous formate, a molecule devoid of any
2
hydrogen bonding.
Glycylglycylglycine. Neutrals. Various conformers of GGG
were previously examined by Zhang et al.,49 and also more
recently by Strittmatter and Williams50 in their attempts to
obtain accurate values for the proton affinity of GGG. While
the proton affinities obtained by both groups are comparable
and agree well with experimental values,51 the level of theory
used in their work is modest by todayÏs standards. The potential energy surface of neutral GGG has been shown to be relatively Ñat with many structures at low energy minima. We
have performed independent conformational searches and
optimized many of the lowest energy conformers at B3LYP/
DZVP (see Table 3 and Fig. 3. The HF/6È31G(d) results of
Zhang et al.49 were taken as starting points in our optimization work. The three lowest energy conformers found
were virtually degenerate and hence, in our endeavor to identify the lowest energy isomer of neutral GGG, all three
isomers considered here were reoptimized with a basis set
Phys. Chem. Chem. Phys., 2001, 3, 853È861
857
including di†use functions [at B3LYP/6È31&&G(d,p)]. This
reconÐrmed that every one of the three structures is at a
minimum, while producing a relative free energy spread of
only 0.2 kcal mol~1. Single-point calculations on all three
isomers were performed at MP2(fc)6È311&&G(2df,2p) using
the optimized geometry of B3LYP/DZVP. The results of these
calculations indicate that 8N and 9N are virtually degenerate
with 9N being favored by only 0.4 kcal mol~1, while 7N is 2.5
kcal mol~1 higher in energy than 9N. This relative order is
probably due to the better description of the intramolecular
hydrogen bonds found in both 8N and 9N by the inclusion of
di†use and extra polarization functions in the larger basis set
used in our MÔllerÈPlesset perturbation (MP2) calculations.
While we do not claim to have deÐnitively identiÐed the structure at the global minimum on the neutral GGG surface, we
have shown that 8N and 9N are essentially degenerate independent of the level of theory and that it is inconsequential to
our study which of these three isomers is used for binding
energy determination.
Glycylglycylglycine-Ag`. Much as in the GGÈAg` complexes, the silver(I) ion demonstrates its ability to act as a
multicoordinate center in GGG-Ag`. The global minimum
found for this surface, structure 10Ag, has a tetracoordinate
Ag` having interactions with the terminal amino group as
well as each of the three carbonyl oxygens of GGG. In order
to allow for this mode of coordination around the central
metal center, the backbone of this tripeptide must undergo a
signiÐcant distortion. The energy cost of this steric requirement is more than compensated by the interactions of Ag`
with the four most electron rich sites of GGG. This is evident
upon comparison of structure 10Ag with structure 14Ag
where the silver ion is chelated only to the terminal nitrogen
and the adjacent carbonyl oxygen. While this mode of coordination allows for a less sterically hindered GGG backbone,
structure 14Ag is calculated to be 3.2 kcal mol~1 higher in
energy than 10Ag ; this highlights the energetic importance of
the secondary interactions of the Ag` with the carbonyl
groups of the second residue and of the carboxylic acid group.
In the dipeptide case, structure 4Ag, which is the analogous
structure of 10Ag on the GGGÈAg` surface, was found to be
higher in energy than 3Ag, the comparable structure to 10Ag.
This is perhaps indicative of the extra stabilization a†orded by
the fourth silverÈligand bond in 10Ag as well as the relatively
higher steric cost associated with folding the shorter GG
backbone in order to allow for the geometry needed for a tricoordinate Ag`.
Structure 12Ag is another conformer that displays the
ability of Ag` to become a multicoordinate center. Here the
silver ion is simultaneously chelated to all three carbonyl
oxygens in GGG. This isomer is nearly degenerate with the
lowest energy isomer 10Ag. Structures 15Ag and 16Ag shown
in Fig. 3 both feature a dicoordinate Ag` and are both about
10 kcal mol~1 higher in free energy relative to 10Ag. The zwitterionic species 17Ag and 19Ag are the highest energy forms
of the GGG-Ag` complex investigated in this work and are
18.9 and 19.6 kcal mol~1, higher in free energy relative to
10Ag.
GlycylglycylglycineÈCu`. All structures investigated were
found to be dicoordinate with respect to the copper ion ; no
structure with higher coordination at Cu` was found to be at
a minimum. The geometry of structure 11Cu, where the Cu`
is coordinated to the carbonyl oxygens on the terminal residues, is such that an angle close to the ideal 180¡ is a†orded
between the metal and the ligands. This favorable coordi-
Table 3 Total electronic energies, unscaled zero-point energies (ZPE), enthalpy corrections, entropies and relative free energies. Upper numbers
are calculated at B3LYP/DZVP, central italicized numbers are calculated at B3LYP/6È31&&G(d,p) and lower bold face numbers are calculated at
MP2(fc)/6È311&&G(2df,2p)//B3LYP/DZVP
Structure
7N
8N
9N
10Ag
12Ag
14Ag
15Ag
16Ag
17Ag
19Ag
11Cu
13Cu
14Cu
15Cu
16Cu
18Cu
19Cu
858
Electronic
energy/
hartree
[700.560 76
[700.510 79
Ô699.207 03
[700.564 44
[700.515 23
Ô699.214 21
[700.565 46
[700.515 46
Ô699.216 78
[5899.873 32
[5899.868 94
[5899.861 70
[5899.855 06
[5899.854 85
[5899.838 23
[5899.838 23
[2340.619 80
[2340.693 56
Ô2338.417 04
[2340.622 14
[2340.693 79
Ô2338.421 87
[2340.598 06
Ô2338.393 31
[2340.612 86
[2340.685 26
Ô2338.411 74
[2340.592 72
Ô2338.388 13
[2340.562 63
Ô2388.360 68
[2340.567 34
Ô2338.361 92
ZPE/
kcal mol~1
H¡ [ H¡/
298mol~1
0
kcal
Entropy/
cal mol~1 K~1
119.8
119.5
9.8
9.8
128.5
129.1
120.8
120.5
9.3
9.3
122.1
122.5
121.1
120.6
9.1
9.2
118.6
121.6
122.1
121.3
121.8
122.3
121.8
120.2
121.7
121.9
121.9
10.3
10.6
10.5
10.3
10.4
10.4
10.5
10.2
10.1
128.4
132.8
135.2
134.1
131.7
133.0
135.8
126.7
125.0
123.2
123.1
9.8
9.8
124.1
124.4
122.1
10.3
131.7
122.8
122.7
9.9
9.9
126.7
126.1
122.1
10.1
127.4
120.7
10.3
130.7
121.8
10.5
134.4
Phys. Chem. Chem. Phys., 2001, 3, 853È861
Relative free
energy at 298 K/
kcal mol~1
0.0
0.2
2.5
0.1
0.1
0.4
0.7
0.0
0.0
0.0
0.9
3.2
10.0
10.4
18.9
19.6
0.0
1.3
1.4
0.2
0.0
0.0
14.6
15.1
5.0
4.6
5.4
19.1
19.4
33.6
33.8
30.8
33.8
Fig. 3 Structures of triglycine and AgÈtriglycine` and CuÈtriglycine` complexes as optimized at B3LYP/DZVP. Upper numbers are for
M \ Ag and bottom italicized numbers are for M \ Cu. Bond lengths are in a- ngstroŽms and angles are in degrees.
nation angle is also present in structure 13Cu, where the coordination sites are the terminal carbonyl and the terminal
amino group. This favorable coordination angle may play a
role in that these isomers are nearly degenerate in free energy.
Structures 15Cu, 14Cu and 16Cu are less energetically favored,
being 5.0, 14.6 and 19.1 kcal mol~1, respectively, higher in free
energy than 11Cu.
The zwitterionic structure 18Cu is yet another example of
Phys. Chem. Chem. Phys., 2001, 3, 853È861
859
Table 4 Binding energies for ions ML` calculated at B3LYP/DZVP.
Bold face values are calculated at MP2(fc)/6È311&&G(2df,2p)//
B3LYP/DZVP. Italicized values are reported at 0 K
DH¡ /kcal mol~1
298
Species
L
NH
3
H CO
2
H NCHO
2
Glycine
(G)
GG
GGG
M \ Ag`
M \ Cu`
40.1
28.5
39.6
48.1
57.9
64.6
49.0a, 49b, 52.2c, 51.8d, 52.3e
42.1, 36.8c
56.9, 56.2c, 52.6c
70.5, 68.6, 68.1f
80.4, 80.3
95.2, 94.8
a Ref. 54. b Ref. 55. c Ref. 56. d Ref. 57. e Ref. 58. f Ref. 23.
the unsymmetrical coordination of Cu` to the CO ~ group in
2
the presence of a hydrogen bond to one of the oxygens in the
CO ~ group. This monocoordination of the metal might be
2
among the reasons for structure 18Cu to have the highest
energy encountered on this surface. Structure 19Cu is another
zwitterionic form of the GGG-Cu` complex ; this structure is
similar to 9Cu on the GG-Cu` surface, in that both of these
ions have the metal center coordinating with both of the
oxygen atoms of the CO ~ group in a nearly symmetrical
2
fashion.
Binding energies
The binding energies of Ag` and Cu` to glycine, diglycine
and triglycine and to some small molecules that contain the
functional groups present in peptides are presented in Table 4,
all corrected for basis set superposition errors (BSSE) by using
the counterpoise method.52,53 At this level of theory the corrections are typically 2È3 kcal mol~1. The binding energies of
all Cu` containing ions considered here are greater than those
of their Ag` analogs. The ligand for which the di†erence in
the binding energies in complexes with the two metal ions is
smallest is NH , the simplest model of the terminal amino
3
group present in a peptide. The di†erence of the binding energies in complexes with H CO, the simplest carbonyl2
containing molecule, is about 14 kcal mol~1. The di†erence of
17 kcal mol~1 for H NCHO is larger still ; this is the simplest
2
model that contains both a terminal amino nitrogen and a
carbonyl functionality. This divergence increases even when
the binding energies to each of glycine, diglycine and triglycine
are considered ; here the di†erences are 20.6, 22.4 and 30.2 kcal
mol~1 respectively.
To the best of our knowledge, the silver ion affinities presented here are the Ðrst values of *H¡ in the literature. The
298
Cu`Èglycine complex has been the subject of previous investigations and the most accurate calculated binding energy available is presented in Table 4. This value of 68.1 kcal mol~1
obtained from CCSD(T) calculations is well reproduced by the
less computationally demanding approach adopted here (see
Table 4).
Conclusions
In all the ML` complexes investigated, the highest coordination number observed for Cu` was found to be two. By
contrast, Ag` does form tri- and tetracoordinate structures.
When Ag` adopts higher coordination, tricoordinate in the
case of diglycine and tri- and tetracoordinate in the case of
triglycine, these structures in all instances were found to be at
low energy minima. Several groups have shown dicoordinate
Cu` complexes always to adopt a linear geometry in the gas
phase. This could be one of the reasons behind the stability of
the two lowest energy structures of the GGGÈCu` complex,
where the angle comprising the two coordinating sites and the
metal is nearly the ideal 180¡.
860
Phys. Chem. Chem. Phys., 2001, 3, 853È861
The binding energies for all the Cu` complexes are all
larger than those of the analogous Ag` species. The di†erence
is found to increase as the size of the ligand increases. As previously reported, the lowest energy isomer of the zwitterionic
form of the CuÈglycine` complex was found to be monocoordinate with respect to the copper ion. Similar structures
were also observed for the GGÈCu` and GGGÈCu` complexes ; however, no equivalent structures were found for Ag`.
Acknowledgements
We are grateful to Steve Quan for technical assistance. We
thank the Natural Sciences and Engineering Research Council
of Canada, MDS SCIEX, the Canadian Foundation for Innovation and the Ontario Innovation Trust for Ðnancial
support. T.S. acknowledges Ðnancial support in the form of an
Ontario Graduate Scholarship in Science and Technology.
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