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AM1 studies of hydrogen bonded adducts between 2,5-dihydroxy-p-quinone and N-bases
THEO CHEM Journal
of Molecular
Structure
(Theochem)
330 (1995)
395-401
~__
AM1 studies of hydrogen bonded adducts between 2,5dihydroxy-p-quinone and N-bases Mario Bossaa, Giorgio bCentro
di Biologia
0. Morpurgoa’*,
Laura Morpurgob
‘Dipartimento di Chimica. Universitir di Roma “La Sapienra”, 00185 Roma, Italy Molecolare del C.N.R.. c/o Dipartimento di Science Biochimiche, Universitir di Roma 00185 Roma, Italy Received
24 September
1993; revised
18 October
1993: accepted
23 December
“La Sapienza”.
1993
Abstract Semiempirical AM1 calculationswere usedto optimize the geometry of the adductsformed by 2,5-dihydroxy-p quinone (DHpQ) with substituted pyridines or imidazole. Hydrogen bond formation wasseento be responsiblefor the
stability of the adducts.From the study of the total energyfunction, obtainedby imposingfixed positionsto the proton, two structureswerefound to be possiblefor eachadduct, oneschematicallyindicatedas-OH . N-base and the proton transfer one, indicated as -OHN+base.The proton transfer energy wasfound to vary linearly with the basepK,,, value. A study was also carried out on the system formed by DHpQ and a cluster of three water molecules acting ;15 proton acceptors.The implicationswerediscussedrelating to possiblehydrogen bond formation betweentrihydroxyphenylalanine quinone, the coenzyme of bovine serum amine oxidase, and some basic residue or water molecule. close to the protein active site.
1. Introduction The quinone of 2,4,5-trihydroxyphenylalanine (TOPA quinone or TPQ) is the coenzyme of the copper containing amine oxidase from bovine serum (BSAO, E.C.1.4.3.6) [l]. This molecule cannot be isolated from the enzyme in the free form because of its high reactivity, but, by exploiting its ability to bind reagents of the carbonyl group, it was isolated as the phenylhydrazone in a pentapeptide fragment, obtained by proteolytic cleavage of reacted BSAO [l]. The information available on TPQ chemistry mostly derives from investigations on the intact enzyme, although * Corresponding
author.
0166-1280/95/$09.50 c SSDI 0166-1280(94)03867-K
1995 Elsevier
Science
B.V.
All rights
lying
some properties could be referred to those of simple and stable TPQ analogues (see Fig. l), such as 5-(2,4,5-trihydroxybenzyl)hydantoin quinone [l], 6-hydroxydopamine quinone [2], and 2,5-dihydroxy-p-quinone (DHpQ) [3,4]. The electronic spectrum of undissociated DHpQ showsa band at 400 nm, which was assignedto the lowest energy T --f T* transition. Dissociation of one of the two protons shifts the band to 485 nm (E = 1350M-’ cm-t) [3], where also BSAO absorbs. In non dissociating solvents, such as CH2C12 and in the presence of N-bases, such as pyridine or imidazole, an equilibrium is established between the species absorbing at 400nm and a species absorbing at 485nm. The re1atk.e amount of the latter species,which was indicated reserved
396
A-4. Bossa et ul.:‘J. Mol.
Struct.
Fig. 1. Quinones. R = alanine. TOPA quinone or TPQ; R = CH2hydantoin, trihydroxybenzylhydantoin; R = CH?CH,NH,, trihydroxyphenethylamine; R = OH, 2,5-dihydroxy-1,4-p-quinone or DHpQ.
by experimental evidence to be a 1 : 1 hydrogen bonded adduct, was larger, the higher was the N-base pK, value. The formation of hydrogen bonded complexes was addressed by the AM1 molecular orbital method [4]. The optimized geometries so far reported describe the -OH.. N bond to correspond to the more stable conformation of the adduct schematically shown in Fig. 2. The importance of the presence of a carbonyl group adjacent to the hydroxyl was stressed. as this assembly appears to orientate N- and other bases.For instance, the plane of the pyridine molecule lies almost parallel to that of DHpQ, being the hydroxyl hydrogen bonded to the nitrogen on one side, and the H(25) bonded to the carbonyl oxygen on the other. When H( 10) moves from O(8) towards N( 15) the energy function is expected to show a double minimum, becauseof formation of the proton transfer species-O- . . . HN’ base [5]. The stabilization of the latter conformation explains the similarity of the DHpQ-base spectra in non dissociating solvents and of the free molecule in water, where the -O- . H-OH speciesis very likely present. The purpose of the present investigation was (i) of extending the geometry optimization to DHpQ adducts with bases other than pyridine, (ii) to determine adduct geometry and energetics for stepwise variations of bond lengths in the 0-H. N li 21
Fig. 2. Scheme
of the DHpQ-pyridine
adduct
[3].
iTheochm)
330 (1995)
395-401
group, (ii) to justify the experimentally found analogiesbetween the spectrum of DHpQ-N-base experimentally found in CH2C12and that of DHpQ in acidic water solutions, (iv) to gain further insight into TPQ reactivity in the catalytic site of HSAO.
2. Methods Energies were calculated and minimized by means of the AM1 method, using MOPAC (version 4.10) [669].
3. Results 3.1. Geometry and energetics To calculate the hydrogen bond energy profile in DHpQ-N-base adducts, the optimized geometry of the more stable conformation was first determined. The calculations were then repeated for imposed O-H distances. The plot of total energy vs. O-H distance gave double minimum curves as that of Fig. 3, which refers to the adduct with pyridine. The deepest minimum was obtained for O-H distances around 1A, the second minimum for O-H distances of 1.G2.OA. In the lattclr case the H-N distance was that of an -inium salt. The two distances agree well with those experimentally determined in similar systems. In Fig. 3 it can be seen that the hydrogen atom yielding the highest interaction energy is that between the quinone O(8) and the baseN(15). A weaker interaction was also established between the quinone O(7) and the base H(25). It is remarkable that the various basesdid not induce differences in the position of the minima in the O-H scale,but only in the energy diflerence between the minima and in the height of the potential energy barrier. It is well known that the relative height of the two minima is sensitive to the pK, value of the proton donor and of the conjugated acid of the acceptor [lo]. In Table 1 are reported the heat of formatilon and the hydrogen bonding energy at the two minima of each calculated total energy vs. the O-H distance. The hydrogen bonding energy is defined as the difference between the algebraic sum of the heat
395
,.‘, O-H Fig. 3. Total distances.
energy
of the DHpQ-pyridine
DISTANCE adduct
(A)
as a function
of formation pertaining to each component of the adduct and the heat of formation of the adduct, calculated at the given O-H distance. The calculated hydrogen bond energies relative to systems in the geometry corresponding to the deepest minimum of the total energy curve, are within weak bond limits. In this case no correlation was found with the base pK, values. On the contrary, a good
of O(X)-H(lO)
distance
and optimized
geometries
at the indicated
linear correlation between bonding energy and pl;, was observed for O-H distances suitable to formation of proton-transfer adducts (Fig. 4). The amount of these adducts. which were observed to form in solution, was an increasing function of the N-base pK,. The values of the hydrogen bond enthalpy (Table 1) are all positive, but it should be recalled that the present AM1 calculations
398 Table 1 Interaction N-base
4-CN Pyridine 4-Me 3,4-Me Imidazole N(Meh 2,6-Me
M. Bossa et al./J.
energies
(E, Kcalmol-i) PK,
1.80 5.28 6.00 6.50 7.20 9.70
a AH(OH ‘. N) and AH(Ostable configurations. AH(DHpQ)
of hydrogen
Mol.
Struct.
bonds
(Theochem)
between
DHpQ
and acceptor
(B)
PHPQ
AH
AH
AH
f64.85 +32.04 +24.16 +17.23 +50.84 f39.33 t19.54
-53.06 -85.88 -93.76 -100.7 -67.07 -78.58 -98.38
-55.36 -88.47 -92.50 -103.1 -70.04 -81.12 -101.5
(OH..
+ B)
HN+) are the total energies = ~ 117.92 kcalmol-’
395-401
N-bases
N)”
(B) (0..
E(1)
HN+)’
E(3)
AH -2.30 -2.60 -1.26 -2.43 -2.96 -2.54 -3.10
of the DHpQ-N-base
deal with structures and energies in gas phase, while solvation or environment effects are known to be an important factor in determining the relative height of the two minima and it is questionable whether AM1 can deal with this problem. As far as the comparison is concerned of the p& effect on hydrogen bonded and proton transfer adducts, it must be considered that in the latter compounds the proton is at the
‘0,
330 11995)
interaction
-30.36 -61.51 -76.49 -83.56 -52.42 -65.99 -74.86 calculated
t22.69 f18.30 -t17.27 +17.12 t14.65 +12.58 ~23.52
for O-H
bonding distance of the nitrogen the influence of the base pK, stronger.
distances
atom, 50 that is pres\.tmably
3.2. Atomic charges Table 2 compares the atomic charges and some of the C-O distances at the given optimized geometry of free DHpQ (1). of some DHpQ-pyridine
4-CN
\
\
\
\
\
\
\ ‘0 py 3,4-k
4-Me\ 79
\
\
\
Imid 0 ‘1
I-N#e>z
I
I 2
I 4
I
6
I 8
\
\
p
\ I
10
PK, Fig. 4. Variation
of hydrogen
bonds
calculated
energy
ot‘the two
in the DHpQ-N-base
adducts
as a function
of the base ph.,
M. Bossa et al./J.
Mol.
Struct.
Table 2 Electronic charges (atomic units) of some atoms and some interatomic distances (A) calculated in correspondence of OH. B structures and, further below. of OHBf structures Q(7)
O(8)
O(9)
O(11)
C(WO(7)
C(4)--O(8)
DHPQ
-0.27
-0.23
-0.27
-0.23
1.24
1.36
4-CN Pyridine N(Mcb 3H20
-0.29 -0.28 -0.28 -0.32
-0.23 -0.23 -0.23 -0.23
-0.27 -0.28 -0.28 -0.27
PO.23 -0.23 -0.23 -0.22
1.24 1.23 1.24 1.24
1.36 I .36 1.36 1.36
4-CN Pyridine NW)2 3Hz0
-0.41 -0.40 -0.40 -0.46
-0.52 -0.51 -0.50 -0.52
-0.38 -0.38 -0.39 -0.35
-0.24 -0.24 -0.25 -0.23
1.25 1.25 1.25 1.25
I .27 1.27 1.27 I .28
hydrogen bonded complexes (2), and of the proton transfer complexes (3). O-H distances are those at the minima of the potential energy curves (seeFig. 3, where the base is pyridine). At the lowest minimum, atomic charges and interatomic distances almost coincide with those of free DHpQ, while a major perturbation of both charges and geometry is caused by the formation of the proton transfer complex. Substantially similar variations were obtained, whatever the bound base. The above results offer a reasonable explanation of the coincidence of the visible band position when the base is varied. The two C-O bonds of proton-transfer adducts
(Theochcml
330 (1995)
395-401
399
have an equal length and the proton. which is at the bonding distance of the pyridine nitrogen, is bifurcated and almost equidistant from the two oxygen atoms. The X-ray structure determination of the adduct of 4-dimethylaminopyridine confirmed this result [ll]. A secondary hydrogen bond i< formed between the carbonyl oxygen and the pyridine C-2 proton (Fig. 3). A peculiar case is that of the complexes of 2,6dimethylpyridine which was analysed to determine the spectroscopic properties of an N-base which. in principle, was considered incapable of acting as ;I bidentate DHpQ ligand becauseof the two methy I groups at C(16) and C(20). The spectrum of this adduct does not differ from that of the other base\ in CH2C12. This somewhat surprising finding can be explained by referring to Fig. 5 where arc reported two optimized geometries of the DHpQ adduct with O(8)-H(lO) distances respectivelq equal to l.OA and 3.0 A. The first structure is that of the adduct in the deepestwell of the energy vs. O-H distance plot, the other is the adduct in one of the secondary minima found when the electronic densities of the DHpQ atoms are comparable with those of the other OP ... HB adducts. In this case, however, the geometry is substantially different, though the pyridine ring is roughly maintained parallel to the quinone ring by the presence of a C-H.. .O interaction of one hydrogen atom of a methyl group with the
2.10 __--
I
,* 3.28
0.44 = 097 A Fig. 5. Optimized
geometries
A
of the DHpQ-2,6-dimethylpyridine
% adduct
Q-H=3.0 at O(8)-H(lO)
A distances
of l.OA
and 3.O.k
400
M.
Basso
et al.,!J.
Mol.
Strucr.
(Theochemj
in DHpQ
- 3Hz0
330
(IY9S)
395-401
f
Fig. 6. Total
energy
as a function
of O(K)-H(
10) distance
carbonyl O(7). The H ..- 0 distance is within the range of this type of bonds (2.04-2.40 8> [12,13]. By inspection of the net atomic charges and geometries of the proton transfer adduct it is possible to trace the origin of the greater stabilization observed with increasing base pK, in the charge left on the base nitrogen. Al1 other parameters (charges and distances) being roughly the same, the nitrogen net charge varies from -0.052 atomic units of elec-
cluster and optimized
geometries
at the indicated
tric charge for the 4-cyanopyridine -0.1121 in the 4-dimethylaminopyridine. 3.3. DHpQ-I-I20
dl>tances.
adduct
to
interaction
The samespectral features were produced by the DHpQ interaction with N-bases or in aqueous medium. This is of particular interest in relation to the behaviour of TPQ in BSAO. TPQ can be
M. Bossa et al.:J.
Mol.
Struct.
envisaged to form a proton transfer complex either with a basic protein residue or with water. Whatever the real situation, these interactions should provide the same perturbation on the quinone chromophore in order to induce same spectral properties. DHpQ was again used as a model and its complexes with water were analyzed by AMl. The AM1 reliability in dealing with hydrogen bonded systems involving water has been questioned, since the method tends to maximize the number of oxygen lone pairs, which are involved in hydrogen bonds. However, AM1 was considered useful in the treatment of large clusters of hydrogen bonded molecules, where saturation of all available lone pairs is attained [14]. Thus three water moleculeswere, one at a time, coordinated to DHpQ and the geometry was optimized after each addition. The final geometry is shown in Fig. 6. As expected, plenty of bifurcated hydrogen bonds were formed. Only one was linear, that between the quinone hydroxyl and 0(15) of the nearby water molecule (0.982A). The presence of water did not produce any charge polarization with respect to the isolated quinone and the geometry was identical to that at the deepestminimum of the total energy vs. O-H distance plot. When the O-H distance was forced to increase, the system tended to form, after a potential barrier, a second minimum, which was determined by resorting to an initial constraint on water coordinates in order to avoid optimization failure for O(S)-H(lO) distances around 1.8OA. The results were used for global optimization. The geometry corresponding to the O-H distance of 1.7OA shows the DHpQ monoanion hydrogen bonded to H30+, the other water molecules being in a general position, as a prelude to their removal from around O(8) and O(7). The charge distribution on DHpQ monoanion (Table 2) is comparable to that previously
(Theochem)
330 11995)
395-401
401
given for a proton transfer complex. When H,O’ was allowed to lose one of its protons towards the bulk of the solvent, reverting the system to DHpQ- . H20, the already described association [3] was obtained. The charge distribution was much less affected than in the bare anion. The emerging picture is that the DHpQ monoanion is hydrogen bonded to a water molecule, with a proton relaying from the bulk of the solution through a chain of hydrogen bonds.
References [l] S.M. Janes. D. Mu, D. Wemmer. A.J. Smith. S. Kaur. D. Maltby, A.L. Burligame and J.P. Klinman, Science. 248 (1990) 981. [2] J.Z. Pedersen, S. El-sherbini. A. Finazzi-Agro and G Rotilio, Biochemistry, 31 (1992) 8. [3] M. Bossa, M. Brahimi, G.O. Morpurgo and L. Morpurgo, J. Mol. Struct. (Theochem), in press. [4] M. Bossa, G.O. Morpurgo and L. Morpurgo. submitted. [5] P. Schuster, G. Zundel and C. Sandorfy, The Hydrogen Bond. North-Holland, Amsterdam, 1976, Vols. 1, 2, 3. [6] MOPAC: A General Molecular Orbital Package, QCPE: 455, 3rd edn. version 2. [7] Dewar Research Group and J.J.P. Stewart, QCPE Bull., 6 (1986) 24a. [8] J.J.P. Stewart, QCPE Bull., 7 (1987). [9] M.J.S. Dewar, E.G. Zoebisch, E.F. Healy and J.J.P. Stewart. J. Am. Chem. Sot.. 107 (1985) 3902. [lo] G.M. Barrow, Spectrochim. Acta, 16 (1960) 799. [l l] M. Bossa, M. Colapietro, G.O. Morpurgo and G. Portalone, in preparation. [12] G.A. Jeffrey and W. Saenger. Hydrogen bonding 111 Biological Structures, Springer-Verlag, Berlin, 199 I, Ch. 10, p. 156. [13] J.J. Dannenberg and E.M. Erleth, Int. J. Quantum Chem., 44 (1992) 869. [14] O.N. Ventura, E.L. Coitino, A. Lledhs and J. Bertran, J. Mol. Struct.. 187 (1989) 55.
of Molecular
Structure
(Theochem)
330 (1995)
395-401
~__
AM1 studies of hydrogen bonded adducts between 2,5dihydroxy-p-quinone and N-bases Mario Bossaa, Giorgio bCentro
di Biologia
0. Morpurgoa’*,
Laura Morpurgob
‘Dipartimento di Chimica. Universitir di Roma “La Sapienra”, 00185 Roma, Italy Molecolare del C.N.R.. c/o Dipartimento di Science Biochimiche, Universitir di Roma 00185 Roma, Italy Received
24 September
1993; revised
18 October
1993: accepted
23 December
“La Sapienza”.
1993
Abstract Semiempirical AM1 calculationswere usedto optimize the geometry of the adductsformed by 2,5-dihydroxy-p quinone (DHpQ) with substituted pyridines or imidazole. Hydrogen bond formation wasseento be responsiblefor the
stability of the adducts.From the study of the total energyfunction, obtainedby imposingfixed positionsto the proton, two structureswerefound to be possiblefor eachadduct, oneschematicallyindicatedas-OH . N-base and the proton transfer one, indicated as -OHN+base.The proton transfer energy wasfound to vary linearly with the basepK,,, value. A study was also carried out on the system formed by DHpQ and a cluster of three water molecules acting ;15 proton acceptors.The implicationswerediscussedrelating to possiblehydrogen bond formation betweentrihydroxyphenylalanine quinone, the coenzyme of bovine serum amine oxidase, and some basic residue or water molecule. close to the protein active site.
1. Introduction The quinone of 2,4,5-trihydroxyphenylalanine (TOPA quinone or TPQ) is the coenzyme of the copper containing amine oxidase from bovine serum (BSAO, E.C.1.4.3.6) [l]. This molecule cannot be isolated from the enzyme in the free form because of its high reactivity, but, by exploiting its ability to bind reagents of the carbonyl group, it was isolated as the phenylhydrazone in a pentapeptide fragment, obtained by proteolytic cleavage of reacted BSAO [l]. The information available on TPQ chemistry mostly derives from investigations on the intact enzyme, although * Corresponding
author.
0166-1280/95/$09.50 c SSDI 0166-1280(94)03867-K
1995 Elsevier
Science
B.V.
All rights
lying
some properties could be referred to those of simple and stable TPQ analogues (see Fig. l), such as 5-(2,4,5-trihydroxybenzyl)hydantoin quinone [l], 6-hydroxydopamine quinone [2], and 2,5-dihydroxy-p-quinone (DHpQ) [3,4]. The electronic spectrum of undissociated DHpQ showsa band at 400 nm, which was assignedto the lowest energy T --f T* transition. Dissociation of one of the two protons shifts the band to 485 nm (E = 1350M-’ cm-t) [3], where also BSAO absorbs. In non dissociating solvents, such as CH2C12 and in the presence of N-bases, such as pyridine or imidazole, an equilibrium is established between the species absorbing at 400nm and a species absorbing at 485nm. The re1atk.e amount of the latter species,which was indicated reserved
396
A-4. Bossa et ul.:‘J. Mol.
Struct.
Fig. 1. Quinones. R = alanine. TOPA quinone or TPQ; R = CH2hydantoin, trihydroxybenzylhydantoin; R = CH?CH,NH,, trihydroxyphenethylamine; R = OH, 2,5-dihydroxy-1,4-p-quinone or DHpQ.
by experimental evidence to be a 1 : 1 hydrogen bonded adduct, was larger, the higher was the N-base pK, value. The formation of hydrogen bonded complexes was addressed by the AM1 molecular orbital method [4]. The optimized geometries so far reported describe the -OH.. N bond to correspond to the more stable conformation of the adduct schematically shown in Fig. 2. The importance of the presence of a carbonyl group adjacent to the hydroxyl was stressed. as this assembly appears to orientate N- and other bases.For instance, the plane of the pyridine molecule lies almost parallel to that of DHpQ, being the hydroxyl hydrogen bonded to the nitrogen on one side, and the H(25) bonded to the carbonyl oxygen on the other. When H( 10) moves from O(8) towards N( 15) the energy function is expected to show a double minimum, becauseof formation of the proton transfer species-O- . . . HN’ base [5]. The stabilization of the latter conformation explains the similarity of the DHpQ-base spectra in non dissociating solvents and of the free molecule in water, where the -O- . H-OH speciesis very likely present. The purpose of the present investigation was (i) of extending the geometry optimization to DHpQ adducts with bases other than pyridine, (ii) to determine adduct geometry and energetics for stepwise variations of bond lengths in the 0-H. N li 21
Fig. 2. Scheme
of the DHpQ-pyridine
adduct
[3].
iTheochm)
330 (1995)
395-401
group, (ii) to justify the experimentally found analogiesbetween the spectrum of DHpQ-N-base experimentally found in CH2C12and that of DHpQ in acidic water solutions, (iv) to gain further insight into TPQ reactivity in the catalytic site of HSAO.
2. Methods Energies were calculated and minimized by means of the AM1 method, using MOPAC (version 4.10) [669].
3. Results 3.1. Geometry and energetics To calculate the hydrogen bond energy profile in DHpQ-N-base adducts, the optimized geometry of the more stable conformation was first determined. The calculations were then repeated for imposed O-H distances. The plot of total energy vs. O-H distance gave double minimum curves as that of Fig. 3, which refers to the adduct with pyridine. The deepest minimum was obtained for O-H distances around 1A, the second minimum for O-H distances of 1.G2.OA. In the lattclr case the H-N distance was that of an -inium salt. The two distances agree well with those experimentally determined in similar systems. In Fig. 3 it can be seen that the hydrogen atom yielding the highest interaction energy is that between the quinone O(8) and the baseN(15). A weaker interaction was also established between the quinone O(7) and the base H(25). It is remarkable that the various basesdid not induce differences in the position of the minima in the O-H scale,but only in the energy diflerence between the minima and in the height of the potential energy barrier. It is well known that the relative height of the two minima is sensitive to the pK, value of the proton donor and of the conjugated acid of the acceptor [lo]. In Table 1 are reported the heat of formatilon and the hydrogen bonding energy at the two minima of each calculated total energy vs. the O-H distance. The hydrogen bonding energy is defined as the difference between the algebraic sum of the heat
395
,.‘, O-H Fig. 3. Total distances.
energy
of the DHpQ-pyridine
DISTANCE adduct
(A)
as a function
of formation pertaining to each component of the adduct and the heat of formation of the adduct, calculated at the given O-H distance. The calculated hydrogen bond energies relative to systems in the geometry corresponding to the deepest minimum of the total energy curve, are within weak bond limits. In this case no correlation was found with the base pK, values. On the contrary, a good
of O(X)-H(lO)
distance
and optimized
geometries
at the indicated
linear correlation between bonding energy and pl;, was observed for O-H distances suitable to formation of proton-transfer adducts (Fig. 4). The amount of these adducts. which were observed to form in solution, was an increasing function of the N-base pK,. The values of the hydrogen bond enthalpy (Table 1) are all positive, but it should be recalled that the present AM1 calculations
398 Table 1 Interaction N-base
4-CN Pyridine 4-Me 3,4-Me Imidazole N(Meh 2,6-Me
M. Bossa et al./J.
energies
(E, Kcalmol-i) PK,
1.80 5.28 6.00 6.50 7.20 9.70
a AH(OH ‘. N) and AH(Ostable configurations. AH(DHpQ)
of hydrogen
Mol.
Struct.
bonds
(Theochem)
between
DHpQ
and acceptor
(B)
PHPQ
AH
AH
AH
f64.85 +32.04 +24.16 +17.23 +50.84 f39.33 t19.54
-53.06 -85.88 -93.76 -100.7 -67.07 -78.58 -98.38
-55.36 -88.47 -92.50 -103.1 -70.04 -81.12 -101.5
(OH..
+ B)
HN+) are the total energies = ~ 117.92 kcalmol-’
395-401
N-bases
N)”
(B) (0..
E(1)
HN+)’
E(3)
AH -2.30 -2.60 -1.26 -2.43 -2.96 -2.54 -3.10
of the DHpQ-N-base
deal with structures and energies in gas phase, while solvation or environment effects are known to be an important factor in determining the relative height of the two minima and it is questionable whether AM1 can deal with this problem. As far as the comparison is concerned of the p& effect on hydrogen bonded and proton transfer adducts, it must be considered that in the latter compounds the proton is at the
‘0,
330 11995)
interaction
-30.36 -61.51 -76.49 -83.56 -52.42 -65.99 -74.86 calculated
t22.69 f18.30 -t17.27 +17.12 t14.65 +12.58 ~23.52
for O-H
bonding distance of the nitrogen the influence of the base pK, stronger.
distances
atom, 50 that is pres\.tmably
3.2. Atomic charges Table 2 compares the atomic charges and some of the C-O distances at the given optimized geometry of free DHpQ (1). of some DHpQ-pyridine
4-CN
\
\
\
\
\
\
\ ‘0 py 3,4-k
4-Me\ 79
\
\
\
Imid 0 ‘1
I-N#e>z
I
I 2
I 4
I
6
I 8
\
\
p
\ I
10
PK, Fig. 4. Variation
of hydrogen
bonds
calculated
energy
ot‘the two
in the DHpQ-N-base
adducts
as a function
of the base ph.,
M. Bossa et al./J.
Mol.
Struct.
Table 2 Electronic charges (atomic units) of some atoms and some interatomic distances (A) calculated in correspondence of OH. B structures and, further below. of OHBf structures Q(7)
O(8)
O(9)
O(11)
C(WO(7)
C(4)--O(8)
DHPQ
-0.27
-0.23
-0.27
-0.23
1.24
1.36
4-CN Pyridine N(Mcb 3H20
-0.29 -0.28 -0.28 -0.32
-0.23 -0.23 -0.23 -0.23
-0.27 -0.28 -0.28 -0.27
PO.23 -0.23 -0.23 -0.22
1.24 1.23 1.24 1.24
1.36 I .36 1.36 1.36
4-CN Pyridine NW)2 3Hz0
-0.41 -0.40 -0.40 -0.46
-0.52 -0.51 -0.50 -0.52
-0.38 -0.38 -0.39 -0.35
-0.24 -0.24 -0.25 -0.23
1.25 1.25 1.25 1.25
I .27 1.27 1.27 I .28
hydrogen bonded complexes (2), and of the proton transfer complexes (3). O-H distances are those at the minima of the potential energy curves (seeFig. 3, where the base is pyridine). At the lowest minimum, atomic charges and interatomic distances almost coincide with those of free DHpQ, while a major perturbation of both charges and geometry is caused by the formation of the proton transfer complex. Substantially similar variations were obtained, whatever the bound base. The above results offer a reasonable explanation of the coincidence of the visible band position when the base is varied. The two C-O bonds of proton-transfer adducts
(Theochcml
330 (1995)
395-401
399
have an equal length and the proton. which is at the bonding distance of the pyridine nitrogen, is bifurcated and almost equidistant from the two oxygen atoms. The X-ray structure determination of the adduct of 4-dimethylaminopyridine confirmed this result [ll]. A secondary hydrogen bond i< formed between the carbonyl oxygen and the pyridine C-2 proton (Fig. 3). A peculiar case is that of the complexes of 2,6dimethylpyridine which was analysed to determine the spectroscopic properties of an N-base which. in principle, was considered incapable of acting as ;I bidentate DHpQ ligand becauseof the two methy I groups at C(16) and C(20). The spectrum of this adduct does not differ from that of the other base\ in CH2C12. This somewhat surprising finding can be explained by referring to Fig. 5 where arc reported two optimized geometries of the DHpQ adduct with O(8)-H(lO) distances respectivelq equal to l.OA and 3.0 A. The first structure is that of the adduct in the deepestwell of the energy vs. O-H distance plot, the other is the adduct in one of the secondary minima found when the electronic densities of the DHpQ atoms are comparable with those of the other OP ... HB adducts. In this case, however, the geometry is substantially different, though the pyridine ring is roughly maintained parallel to the quinone ring by the presence of a C-H.. .O interaction of one hydrogen atom of a methyl group with the
2.10 __--
I
,* 3.28
0.44 = 097 A Fig. 5. Optimized
geometries
A
of the DHpQ-2,6-dimethylpyridine
% adduct
Q-H=3.0 at O(8)-H(lO)
A distances
of l.OA
and 3.O.k
400
M.
Basso
et al.,!J.
Mol.
Strucr.
(Theochemj
in DHpQ
- 3Hz0
330
(IY9S)
395-401
f
Fig. 6. Total
energy
as a function
of O(K)-H(
10) distance
carbonyl O(7). The H ..- 0 distance is within the range of this type of bonds (2.04-2.40 8> [12,13]. By inspection of the net atomic charges and geometries of the proton transfer adduct it is possible to trace the origin of the greater stabilization observed with increasing base pK, in the charge left on the base nitrogen. Al1 other parameters (charges and distances) being roughly the same, the nitrogen net charge varies from -0.052 atomic units of elec-
cluster and optimized
geometries
at the indicated
tric charge for the 4-cyanopyridine -0.1121 in the 4-dimethylaminopyridine. 3.3. DHpQ-I-I20
dl>tances.
adduct
to
interaction
The samespectral features were produced by the DHpQ interaction with N-bases or in aqueous medium. This is of particular interest in relation to the behaviour of TPQ in BSAO. TPQ can be
M. Bossa et al.:J.
Mol.
Struct.
envisaged to form a proton transfer complex either with a basic protein residue or with water. Whatever the real situation, these interactions should provide the same perturbation on the quinone chromophore in order to induce same spectral properties. DHpQ was again used as a model and its complexes with water were analyzed by AMl. The AM1 reliability in dealing with hydrogen bonded systems involving water has been questioned, since the method tends to maximize the number of oxygen lone pairs, which are involved in hydrogen bonds. However, AM1 was considered useful in the treatment of large clusters of hydrogen bonded molecules, where saturation of all available lone pairs is attained [14]. Thus three water moleculeswere, one at a time, coordinated to DHpQ and the geometry was optimized after each addition. The final geometry is shown in Fig. 6. As expected, plenty of bifurcated hydrogen bonds were formed. Only one was linear, that between the quinone hydroxyl and 0(15) of the nearby water molecule (0.982A). The presence of water did not produce any charge polarization with respect to the isolated quinone and the geometry was identical to that at the deepestminimum of the total energy vs. O-H distance plot. When the O-H distance was forced to increase, the system tended to form, after a potential barrier, a second minimum, which was determined by resorting to an initial constraint on water coordinates in order to avoid optimization failure for O(S)-H(lO) distances around 1.8OA. The results were used for global optimization. The geometry corresponding to the O-H distance of 1.7OA shows the DHpQ monoanion hydrogen bonded to H30+, the other water molecules being in a general position, as a prelude to their removal from around O(8) and O(7). The charge distribution on DHpQ monoanion (Table 2) is comparable to that previously
(Theochem)
330 11995)
395-401
401
given for a proton transfer complex. When H,O’ was allowed to lose one of its protons towards the bulk of the solvent, reverting the system to DHpQ- . H20, the already described association [3] was obtained. The charge distribution was much less affected than in the bare anion. The emerging picture is that the DHpQ monoanion is hydrogen bonded to a water molecule, with a proton relaying from the bulk of the solution through a chain of hydrogen bonds.
References [l] S.M. Janes. D. Mu, D. Wemmer. A.J. Smith. S. Kaur. D. Maltby, A.L. Burligame and J.P. Klinman, Science. 248 (1990) 981. [2] J.Z. Pedersen, S. El-sherbini. A. Finazzi-Agro and G Rotilio, Biochemistry, 31 (1992) 8. [3] M. Bossa, M. Brahimi, G.O. Morpurgo and L. Morpurgo, J. Mol. Struct. (Theochem), in press. [4] M. Bossa, G.O. Morpurgo and L. Morpurgo. submitted. [5] P. Schuster, G. Zundel and C. Sandorfy, The Hydrogen Bond. North-Holland, Amsterdam, 1976, Vols. 1, 2, 3. [6] MOPAC: A General Molecular Orbital Package, QCPE: 455, 3rd edn. version 2. [7] Dewar Research Group and J.J.P. Stewart, QCPE Bull., 6 (1986) 24a. [8] J.J.P. Stewart, QCPE Bull., 7 (1987). [9] M.J.S. Dewar, E.G. Zoebisch, E.F. Healy and J.J.P. Stewart. J. Am. Chem. Sot.. 107 (1985) 3902. [lo] G.M. Barrow, Spectrochim. Acta, 16 (1960) 799. [l l] M. Bossa, M. Colapietro, G.O. Morpurgo and G. Portalone, in preparation. [12] G.A. Jeffrey and W. Saenger. Hydrogen bonding 111 Biological Structures, Springer-Verlag, Berlin, 199 I, Ch. 10, p. 156. [13] J.J. Dannenberg and E.M. Erleth, Int. J. Quantum Chem., 44 (1992) 869. [14] O.N. Ventura, E.L. Coitino, A. Lledhs and J. Bertran, J. Mol. Struct.. 187 (1989) 55.