3274
J. Phys. Chem. B 2007, 111, 3274-3279
Calculations on the Electronic Excited States of Ureas and Oligoureas Mark T. Oakley,† Gilles Guichard,‡ and Jonathan D. Hirst*,† School of Chemistry, UniVersity of Nottingham, UniVersity Park, Nottingham, NG7 2RD, United Kingdom, and CNRS, Institut de Biologie Mole´ culaire et Cellulaire, Laboratoire d’ Immunologie et Chimie The´ rapeutiques, 15 rue Rene´ Descartes, F-67084, Strasbourg Cedex, France ReceiVed: NoVember 28, 2006; In Final Form: January 23, 2007
We report CASPT2 calculations on the electronic excited states of several ureas. For monoureas, we find an electric dipole forbidden n f π* transition between 180 and 210 nm, dependent on the geometry and substituents of the urea. We find two intense πnb f π* transitions between 150 and 210 nm, which account for the absorptions seen in the experimental spectra. The n′ f π* and πb f π* transitions are at wavelengths below 125 nm, which is below the lower limit of the experimental spectra. Parameter sets modeling the charge densities of the electronic transitions have been derived and permit calculations on larger oligoureas, using the exciton matrix method. For glycouril, a urea dimer, both the CASPT2 method and the matrix method yield similar results. Calculations of the electronic circular dichroism spectrum of an oligourea containing eight urea groups indicate that the experimental spectrum cannot be reproduced without the inclusion of electronic excitations involving the side chains. These calculations are one of the first attempts to understand the relationship between the structure and excited states of this class of macromolecule.
Introduction The tendency of polypeptides to form regular secondary structures is well-known and is important for their biological activity. Much research has focused on the synthesis of compounds that are not based on R-peptides, yet still form regular structures.1 Compounds containing amide groups that are separated by two or three carbon atoms (β- and γ-peptides) have received a great deal of attention.1-4 The repeating unit need not be an amide and helical oligoureas have also been synthesized.5-8 These compounds adopt a 2.5-helical structure, i.e., each turn of the helix consists of two residues with a rise of 5 Å, which is stabilized by the formation of two hydrogen bonds between the i and i + 2 urea groups.6 These compounds have antibacterial properties9 and may have other biomedical uses. Electronic circular dichroism (CD) is used widely in the study of polypeptides, because different secondary structural elements have characteristic CD spectra. Much effort has been put into developing methods to calculate the CD spectra of polypeptides, from Moffitt’s original calculation of the spectrum of the R-helix10 to recent studies based on ab initio calculations.11,12 The most frequently used approach is the exciton matrix method,13,14 which treats a protein as a collection of separate chromophores that interact with each other electrostatically. The CD spectra of several types of foldamer have also been reported,5,7,15,16 but the relationship between the spectrum and the secondary structure is not as well understood as it is for R-peptides. Seebach and co-workers have measured the CD spectra of β-peptide foldamers and have also calculated the CD spectra of these compounds using the matrix method.15,16 The matrix method reproduced the experimental spectra but, unlike R-peptides, different types of secondary structure in β-peptides can produce similar CD spectra. The spectra of β-peptides have also been calculated by using the dipole interaction method, which considers only the amide πnb f π* band.17,18 † ‡
The CD spectra of several oligoureas have been recorded, with the most prominent feature being an intense positive band at 203 nm.6,7 The relationship between the CD spectra and structures is less well understood for oligoureas than it is for β-peptides and matrix method calculations could provide some insight. To perform such calculations, we need to know the electronic structure and transition properties of simple ureas. The molecular orbitals involved in the electronic transitions seen in the UV spectra of ureas should be similar to those in amides. Urea has four p orbitals (Figure 1): one bonding (πb), two nonbonding (πnb1, with a node along the CO bond and πnb2, with a node perpendicular to the CO bond), and one antibonding (π*). In the σ system there are three important orbitals (Figure 2): two lone pairs on the oxygen atom (n and n′) and an antibonding σ* orbital. There have been few experimental studies of the UV spectroscopy of ureas. Campbell and Clark recorded polarized vacuum UV spectra of crystalline urea (1a).19 They found a transition at 176 nm with B1 symmetry, which they assigned to the πnb1 f π* excitation, and one at 158 nm with A1 symmetry, assigned to the πnb2 f π* excitation. A third transition at 153 nm with B1 symmetry was later assigned to the n f σ* excitation.20 They were unable to find an n f π* excitation, but this transition is electric dipole forbidden and would be very weak and buried by the π f π* bands. The spectrum of dimethylurea (1b) has only been recorded down to 200 nm, with an absorption centered somewhere below the lower end of the spectrum.21 In the solution-phase spectrum of tetramethylurea (1c) there are two intense absorption bands at 202 and 176 nm.
University of Nottingham. E-mail:
[email protected] Institut de Biologie Mole´culaire et Cellulaire.
10.1021/jp067890a CCC: $37.00 © 2007 American Chemical Society Published on Web 03/03/2007
Electronic Excited States of Ureas and Oligoureas
J. Phys. Chem. B, Vol. 111, No. 12, 2007 3275 Computational Methods
Figure 1. The πb, πnb1, πnb2, and π* molecular orbitals of urea.
Figure 2. The n′, n, and σ* molecular orbitals of urea.
There have been several calculations of the excited states of urea.22-24 The most recent involved the use of several types of coupled cluster calculations on urea25 and the best results were obtained by using the CCR(3)/daug-cc-pVTZ method,26 a coupled cluster response approach with a doubly augmented correlation-consistent triple-ζ basis set. In these calculations, the three lowest energy valence transitions were located between 190 and 195 nm and corresponded to excitations to the σ* orbital. None of these transitions was seen in the experimental spectrum. The electric dipole forbidden n f π* transition was next at 185 nm (f < 0.001) and the πnb1 f π* and πnb2 f π* transitions appeared at 159 (f ) 0.130) and 164 nm (f ) 0.047). Polarized vacuum UV spectra of glycouril (3), a diurea, have also been reported.20 These spectra give further insight into the nature of the urea chromophore and also provide information about the coupling between ureas. Calculations using the independent systems model (closely related to the matrix method) and the experimental transition properties of urea reproduced the experimental spectrum of glycouril well, showing that it behaves as two electrostatically coupled urea chromophores. The cyclic urea 2-imidazolidinone (2) is a good model of the urea chromophore in glycouril, but its UV spectrum has not been recorded. We present calculations on the excited states of several simple ureas using high-level quantum chemical calculations with the aim of reproducing their experimental spectra and providing model systems for matrix method calculations. Glycouril is an interesting case, because it is small enough to be amenable to ab initio calculations, but it also contains two urea groups so it can be subjected to matrix method calculations. Previously, both of these approaches were used to calculate the UV spectrum of the cyclic diamides.27,28 These calculations revealed that the coupling between the amides was mainly electrostatic, and similar calculations on glycouril can be used to study the coupling between ureas. Compound 4 is an oligourea that has a published CD spectrum and has also had a series of threedimensional structures determined by NMR spectroscopy. We present the CD spectra of these structures calculated using the matrix method. A greater understanding of the electronic structure of oligoureas should be helpful in interpreting the optical spectroscopy of these interesting foldamers.
The geometries of compounds 1a-c and 2 were optimized at the MP2/6-31G(d) level using Q-Chem.29 Frequency calculations were performed to characterize the structures as minima or higher order stationary points. The monoureas, 1a-c, each have three conformations to be considered: one with C2V symmetry where the nitrogen atoms are planar and two where the nitrogen atoms are pyramidal with Cs and C2 symmetry. The excited-state properties were calculated with MOLCAS.30 Transition energies were generated by using the complete active space self-consistent field (CASSCF) method31 with the CASPT2 correction for electron correlation32 and transition dipole moments were calculated by using the RASSI method.33 The effect of the basis set on the transition properties was studied by performing calculations on the C2V structure of urea, using a range of ANO basis sets.34 These included a set contracted to 4s3p1d for C, O, and N atoms and 2s1p for H atoms and a larger basis set contracted to 5s4p2d1f/3s2p1d. In addition, a basis set contracted to 4s3p1d/2s1p was augmented with a set of off-atom diffuse functions (1s1p1d) to model the Rydberg orbitals.35 All of the calculations on the other monoureas were performed with the 4s3p1d/2s1p basis set augmented with diffuse functions. The calculations on glycouril were performed with the 4s3p1d/2s1p basis set with no diffuse functions. The active space for these calculations must include all orbitals that are involved in the excitations. Calculations on compounds 1a-c and 2 were all carried out by using the orbitals shown in Figures 1 and 2, plus one or two additional unoccupied orbitals that were needed to aid the convergence of the CASSCF calculations. In this investigation, we are only interested in the valence states of ureas so, in all calculations, any Rydberg orbitals lying below the valence orbitals were deleted. Details of the active space used for each compound are presented in the appropriate tables. We use the notation (i1,i2,i3,i4;j1,j2,j3,j4) to describe the active space, where in is the number of closed orbitals of a given symmetry and jn is the number of active plus closed orbitals of the same symmetry. The indices, n, are the symmetry labels from MOLCAS (for C2V, 1 ) a1, 2 ) b1, 3 ) b2, 4 ) a2; for C2, 1 ) a, 2 ) b; for Cs, 1 ) a′, 2 ) a′′). The CD spectra of oligoureas were generated by using the matrix method,13 which treats the system as a collection of coupled chromophores. In the matrix method, a Hamiltonian matrix is constructed in which the diagonal elements are the transition energies of the isolated chromophores and the offdiagonal elements are the electrostatic coupling between them. These couplings are the integrals of coulomb interactions between the transition densities; the latter are approximated by collections of point charges for computational expediency. Diagonalization of this matrix gives the coupled transition energies and a set of eigenvalues that can be used to generate the transition dipole moments of the macromolecule. Parameters describing the transition densities of the urea chromophore were generated from the transition properties of the C2V structures of urea and dimethylurea. For technical reasons, these parameters are based on ab initio calculations using the C2V structure, but with a C1 symmetric wave function, which have transition properties close to those run in C2V symmetry. For each transition density, the associated electrostatic potential was generated with MOLPRO,36 and 48 point charges were fitted to reproduce the potential for each transition, with eight charges arranged at the corners of a cube with edges of length 0.1 au around each of the urea C, O, and N atoms and the two H atoms in the R2 position. These parameters are available as Supporting Information.
3276 J. Phys. Chem. B, Vol. 111, No. 12, 2007
Oakley et al. TABLE 2: The Transition Properties of the C2W Structure of Urea with Different Basis Sets 4s3p1d n f π* πnb1 f π* πnb2 f π* n′ f π* πb f π*
Figure 3. A typical structure of oligourea 4.
TABLE 1: Energies of the Conformations of Ureas Relative to the C2 Conformer compd
C2 energy/au
C2V/kJ mol-1
Cs/kJ mol-1
O-C-N-R2 dihedral/deg
1a 1b 1c
-224.6193 -302.9492 -381.2570
4.5 3.6 44.0
4.7 2.9 40.1
146 151 137
CASSCF calculations on glycouril comprising all of the orbitals used in the calculations on the monoureas would lead to an active space that is too large, so the πb and n′ orbitals were removed from the active space and the off-atom diffuse orbitals were also omitted. Calculations on 2-imidazolidinone were also performed with this smaller group of orbitals for comparison. All of these calculations used the published crystal structure of glycouril.37 The CD spectra of a set of 20 structures of oligourea 4, derived from NMR spectra measured in deuterated methanol and 280 K,7 were calculated with use of urea parameters from urea and dimethylurea. The parameters for the aromatic side chains were based on ab initio calculations on phenol previously used as a model for the side chain in tyrosine.38 These parameters include transitions to the 1Lb, 1La, 1Ba, and 1Bb states at 274 (f ) 0.008), 216 (f ) 0.026), 196 (f ) 0.807), and 192 nm (f ) 0.699). Results and Discussion For the monoureas, the structure with C2 symmetry is the global energy minimum. The C2V structure is a second-order transition state corresponding to the simultaneous inversion of both nitrogen atoms (infrared frequencies and intensities are provided in the Supporting Information). In both urea and dimethylurea the difference in energy between all three structures is small (Table 1). In tetramethylurea, the steric effect of the two extra methyl groups leads to the C2 structure being the most stable by more than 40 kJ mol-1 (Table 1). Moving away
4s3p1d + diffuse
5s4p2d1f
exptl19
E/nm
f
E/nm
f
E/nm
f
E/nm
f
184 164 156 109 101
0.000 0.366 0.361 0.040 0.007
181 157 153 108 100
0.000 0.366 0.361 0.040 0.010
189 179 166 112 106
0.000 0.322 0.369 0.039 0.001
n/a 176 158 n/a n/a
n/a 0.205 0.227 n/a n/a
from C2V symmetry has a substantial effect on the n f π* transition, which shifts to a longer wavelength by 10-25 nm and increases in intensity. However, changes to the geometry make much smaller differences to the other transitions (Table 3). The choice of basis set has some effect on the calculated transition energies (Table 2). The πnb1fπ* transition has the largest basis set dependence, with the 5s4p2d1f basis set close to the experimental energy and the other two basis sets overestimating the energy by a significant margin. The energy of the πnb2 f π* transition varies much less with the basis set and, in this case, using the 5s4p2d1f basis set gives the worst results. There are no experimental values with which to compare the other three transition energies. The best compromise between the completeness of the basis set and the computational resources required is obtained with the 4s3p1d basis set with additional diffuse functions. The experimental UV spectrum19 of urea was obtained by polarized reflection spectroscopy from single crystals. By using this method, the spectra along each of the crystal axes can be recorded, which allows the symmetry of the transitions to be determined. In the crystal phase, urea adopts a C2V structure, so the experimental spectrum can be compared to the calculated C2V spectrum. Intermolecular interactions can have a substantial effect on excitations in the crystal phase. Campbell and Clark have accounted for this by making a model spectrum of urea, which reproduces the experimental spectrum after an exciton mixing calculation. We compare our calculated spectrum to this model spectrum. It is worth noting that we are comparing calculated gas-phase vertical excitations with experimental crystal phase measurements so perfect agreement between the two should not be expected. In our calculations, all of the atoms are located in the xy-plane, with the C-O bond pointing along the y-axis. The n f π* transition occurs at 181 nm, but it is electric dipole forbidden and has an oscillator strength (f) of zero, so one would not expect it to be observable. In the experimental spectrum, there are two bands at 176 (f ) 0.205) and 158 nm (f ) 0.227), which were assigned to the πnb1 f π* and πnb2 f π* transitions, respectively. In the calculated spectrum these occur at 157 and 153 nm, i.e., there is good agreement for the πnb2 f π* transition, but less so for the πnb1 f π* transition. The directions of the calculated transition dipole moments of these two excitations (Table 4) are consistent with those in the experimental measurements. The energies of the first three transitions from our calculations are close to those calculated with the CCR(3)/daug-cc-pVTZ method.25 The next peak in the experimental spectrum occurs at 153 nm (f ) 0.088). This transition has B2 symmetry and was assigned to an n f σ* transition. The next two transitions in the calculated spectrum are n′ f π* and πb f π*, which are both of much higher energy than the experimental transition and also have the wrong symmetry. We have been unable to locate the n f σ* transition, which leads us to believe that the n f σ* is a very high-energy transition, as it is in amides.
Electronic Excited States of Ureas and Oligoureas
J. Phys. Chem. B, Vol. 111, No. 12, 2007 3277
TABLE 3: Energies (E) and Oscillator Strengths (f) of the Electronic Transitions of Urea C2V (7,4,0,0;9,6,3,2) n f π* πnb1 f π* πnb2 f π* n′ f π* πb f π*
C2 (7,4;10,9)
Cs (7,4;12,7)
E/nm
f
E/nm
f
E/nm
f
E/nm
181 157 153 108 100
0.000 0.366 0.361 0.040 0.010
197 161 154 113 107
0.004 0.247 0.339 0.052 0.002
196 161 161 113 105
0.005 0.290 0.373 0.029 0.036
185 159 164 n/a n/a
TABLE 4: Properties of the Electronic Transitions in the C2W Structure of Urea electric transition dipole moment/debye n f π* πnb1 f π* πnb2 f π* n′ f π* πb f π*
magnetic transition dipole moment/ Bohr magneton
x
y
z
x
y
z
0.00 3.37 0.00 0.00 0.00
0.00 0.00 -3.60 0.00 -0.36
0.00 0.00 0.00 -0.96 0.00
0.00 0.00 0.00 1.55 0.00
0.74 0.00 0.00 0.00 0.00
0.00 0.11 0.00 0.00 0.00
TABLE 5: Energies (E) and Oscillator Strengths (f) of the Electronic Transitions of Dimethylurea C2V (10,7,1,1;12,9,4,3) C2 (11,8;14,13) Cs (11,8;15,12) E/nm n f π* πnb1 f π* πnb2 f π* n′ f π* πb f π*
f
179 177 158 n/a 108
0.000 0.358 0.302 n/a 0.000
E/nm
f
E/nm
f
191 183 157 n/a 113
0.004 0.321 0.282 n/a 0.002
190 177 164 113 111
0.004 0.321 0.303 0.025 0.011
TABLE 6: Properties of the Electronic Transitions in the C2W Structure of Dimethylurea. electric transition dipole moment/debye n f π* πnb1 f π* πnb2 f π* πb f π*
coupled cluster25
magnetic transition dipole moment/Bohr magneton
x
y
z
x
y
z
0.00 3.23 0.00 0.00
0.00 0.00 -3.15 -0.53
0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00
-0.88 0.00 0.00 0.00
0.00 -0.05 0.00 0.00
The methyl groups on the nitrogen atoms in di- and tetramethylurea have a substantial effect on the excited states. The addition of two methyl groups to urea to make dimethylurea has the greatest effect on the πnb1 f π* transition, which shifts to a lower energy by 20 nm (Table 5). The transition dipole moments of all excitations are similar those in urea (Table 6). The addition of two more methyl groups to make tetramethylurea shifts all of the transitions to a lower energy by 10-30 nm (Table 7). The differences between the spectra of urea and 2-imidazolidinone are relatively small, with the n f π* transition 8 nm higher in energy and the πnb f π* transition 8 nm lower in energy in 2-imidazolidinone than the corresponding transitions in urea (Table 8). The use of a smaller active space leads to only a small change in the transition properties of 2-imidazolidinone, justifying the use of this active space for calculations on glycouril. There are four absorptions in the experimental UV spectrum of glycouril at 183 (f ) 0.26), 166 (f ) 0.49), 156 (f ) 0.12), and 151 nm (f ) 0.24), which were assigned to πnb1 f π*, πnb2 f π*, πnb2 f π*, and n f σ* excitations, respectively. The matrix method calculations give six excitations corresponding to the in- and out-of-phase combinations of the pairs of n f π*, πnb1 f π*, and πnb2 f π* excitations in the urea chromophore (Table 9). The n f π* excitations occur at 182 nm, but they are electric dipole forbidden, as in urea. The inphase combination of πnb1 f π* excitations is at 169 nm,
f 0.000 0.130 0.047 n/a n/a
exptl19 E/nm
f
n/a 176 158 n/a n/a
n/a 0.205 0.227 n/a n/a
substantially higher in energy than the experimental value. The parameters used in this calculation are based on the CASPT2 calculations on urea, which also give the πnb1 f π* too high an energy (Table 3). The out-of-phase combination is at 170 nm, but it has an oscillator strength of zero. The in- and outof-phase combinations of πnb2 f π* excitations are at 160 and 158 nm, and correspond to the experimental transitions at 166 and 156 nm, respectively. The splitting between pairs of transitions is rather small, with the n f π* transitions split by less than 0.1 nm, the πnb1 f π* transitions by 2.0 nm, and the πnb2 f π* transitions by 1.2 nm. Analysis of the Hamiltonian matrix reveals more details about the coupling between the urea groups. There are large couplings between the πnb2 f π* transitions (341 cm-1) and a slightly smaller coupling between πnb1 f π* (234 cm-1) transitions. There are also small couplings (-16 cm-1) between the n f π* and πnb2 f π* transitions on the same urea group. All of the other matrix elements are zero. In the ab initio calculations, we have to consider a total of 12 transitions. The six lowest energy transitions correspond to the transitions generated by the matrix method. The other six transitions do not correspond to simple in- and out-of-phase combinations of the urea excitations and would be chargetransfer transitions in a less symmetrical system. The properties of the n f π* and πnb2 f π* transitions from the ab initio calculations are in good agreement with those from the matrix method calculations and experimental measurements. These calculations place the in-phase combination of πnb1 f π* transitions at a wavelength 30 nm shorter than the experimental value, which is a rather large difference but it is consistent with the high calculated energy of the πnb1 f π* seen in urea (Table 3). A noteworthy difference between the matrix method and CASPT2 calculations is the larger splitting between the pairs of transitions (2.3 nm for n f π* and 3.5 nm for πnb2 f π*). The splitting between πnb1 f π* transitions is substantially larger at 11.6 nm. The distance between the nitrogen atoms on different urea groups is only 2.43 Å, which is less than the sum of their van der Waals radii and close enough for effects other than electrostatic coupling to influence the transitions. The πnb1 orbitals are localized mainly on the urea nitrogen atoms so one would expect the matrix method to perform less well on transitions involving these orbitals. The other six transitions occur at wavelengths of 141 nm or shorter, beyond the shortest wavelengths recorded in the experimental spectra, and none of them has a substantial oscillator strength. The experimental CD spectra of 4 and other oligoureas possess an intense positive band at 203 nm. Our calculations on urea and dimethylurea place the n f π* transition between 176 and 201 nm, depending on the substituents and geometry of the urea, so this is a possible source of the experimental band. The intense πnb1 f π* and πnb2 f π* are at wavelengths shorter than 181 nm in both the experimental and calculated spectra, so these are unlikely to be the cause of the 203 nm band. The calculated CD spectrum of 4 (averaged over all 20 structures) is presented in Figure 4. When using only transitions from the backbone urea chromophores, the intense band seen at 203 nm
3278 J. Phys. Chem. B, Vol. 111, No. 12, 2007
Oakley et al.
TABLE 7: Energies (E) and Oscillator Strengths (f) of the Electronic Transitions of Tetramethylurea C2V (13,10,2,2;15,12,5,4) E/nm n f π* πnb1 f π* πnb2 f π* n′ f π* πb f π*
C2 (15,12;18,17)
f
187 196 178 n/a 116
E/nm
0.000 0.256 0.342 n/a 0.069
212 212 175 n/a 124
TABLE 8: Energies (E) and Oscillator Strengths (f) of the Electronic Transitions of 2-Imidazolidinone large active space (10,6,1,1;12,8,4,3)
small active space (11,6,2,1;11,8,4,3)
E/nm
f
E/nm
176 173 156 104
0.000 0.230 0.389 0.003
n f π* πnb1 f π* πnb2 f π* πb f π*
177 178 153 n/a
f 0.000 0.223 0.350 n/a
TABLE 9: Transitions of Glycouril from Matrix Method Calculations transition dipole moment/debye n f π* n f π* πnb1 f π* πnb1 f π* πnb2 f π* πnb2 f π*
exptl20
f 0.006 0.208 0.287 n/a 0.015
exptl19
Cs (15,12;20,16) E/nm
f
E/nm
f
207 202 181 117 120
0.012 0.272 0.311 0.000 0.010
n/a 202 176 n/a n/a
n/a n/a n/a n/a n/a
by using only the backbone chromophores, there is little difference between each of the spectra. However, when the side chain chromophores are included (Figure 5), there is much more variation, with the changes caused by different orientations of the aromatic side chains. Analysis of the Hamiltonian matrix elements shows that the coupling between the urea chromophores is not very strong, with the coupling between πnb f π* excitations generally less than 100 cm-1. The coupling between urea and side chain chromophore is even smaller. By far the largest couplings occur between neighboring side chains, especially between the 1Ba and 1Bb states, where the coupling can be as high as 800 cm-1. Conclusions
E/nm
f
x
y
z
E/nm
f
182 182 171 169 160 158
0.000 0.000 0.000 0.574 0.458 0.130
0.00 0.00 0.00 0.00 3.94 0.00
0.00 -0.02 0.00 -4.54 0.00 0.00
0.00 0.00 0.00 0.00 0.00 2.09
n/a n/a n/a 183 166 156
n/a n/a n/a 0.26 0.49 0.12
We have shown that CASSCF/CASPT2 calculations are capable of reproducing most of the experimental UV transitions of simple ureas and a urea dimer, although the source of the absorption at 153 nm in urea still remains a mystery. We have also shown that the matrix method provides a good model of the coupling between urea chromophores in glycouril. The
TABLE 10: Transitions of Glycouril from CASSCF/ CASPT2 Calculations transition dipole moment/debye A2 B2 A2 B1 A1 B2 B2 A2 A2 A1 B2 B1
n f π* n f π* πnb1 f π* πnb2 f π* πnb2 f π* πnb1 f π* πnb1 f π* n f π* πnb1 f π* πnb2 f π* n f π* πnb2 f π*
E/nm
f
184 182 165 158 155 153 141 135 133 132 132 131
0.000 0.006 0.000 0.668 0.204 0.452 0.007 0.000 0.000 0.000 0.004 0.019
x
y
z
0.00 0.00 0.00 0.00 0.50 0.00 0.00 0.00 0.00 4.74 0.00 0.00 0.00 0.00 -2.59 0.00 -3.84 0.00 0.00 -0.46 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 -0.05 0.00 -0.34 0.00 0.72 0.00 0.00
exptl20 E/nm
f
n/a n/a n/a 166 156 183 n/a n/a n/a n/a n/a n/a
n/a n/a n/a 0.49 0.12 0.26 n/a n/a n/a n/a n/a n/a
in the experimental spectrum is missing. The calculated CD spectrum using the urea chromophore consists of a very weak negative band centered at 189 nm from n f π*, a weak positive band at 167 nm, and a weak negative band at 149 nm. Using dimethylurea as a model shifts these peaks to 199, 176, and 153 nm and leads to a slightly lower intensity for all of them. Analysis of the eigenvectors shows that each band can be assigned almost exclusively to the n f π*, πnb1 f π*, and πnb2 f π* transitions, respectively. Conventional CD spectrometers would not detect most of these bands, because they cannot record spectra at wavelengths shorter than 178 nm. According to these calculations, the intense positive band seen at 203 nm in the experimental CD spectra of oligoureas does not come from transitions of the urea chromophore. When the aromatic side groups are included, there is an intense positive peak at 202 nm, which is in good agreement with the wavelength and intensity of the experimental band. When the CD spectrum of each of the 20 structures is calculated
Figure 4. Calculated CD spectrum of 4, using urea chromophore (blue), dimethylurea chromophore (red), and dimethylurea chromophore with side chains (green).
Figure 5. Calculated spectra of 20 structures of 4.
Electronic Excited States of Ureas and Oligoureas calculated spectrum of oligourea 4 consists only of weak highenergy bands when only the urea chromophores are used and it is only with the inclusion of side-chain transitions that the intense band at 203 nm is seen. The most intense bands caused by the urea groups occur at wavelengths shorter than 185 nm, the lowest wavelength at which the experimental CD spectra of oligoureas have been recorded. The lower limit can be extended by a few nm by recording the spectra at higher concentrations and using short path length cells, but the only way to see the predicted bands at much shorter wavelengths is to use synchrotron radiation CD, which can record CD spectra down to 160 nm.39 Another area of potential further study relates to the barrier to the rotation around the C-N bonds, which is substantially lower in ureas than in amides.40 It is possible that some of the urea groups in oligoureas are in cis/trans or cis/cis conformations instead of the trans/trans conformation used in our calculations and that this could have a significant effect on the resulting CD spectra. We will investigate this in future studies. Acknowledgment. We thank Owen Bowyer for his efforts on some preliminary calculations and the Engineering and Physical Sciences Research Council (EPSRC) for funding (grant number GR/T09224). We are also grateful for support from the EU NoE BIOPATTERN (contract no FP6-508803). Supporting Information Available: Coordinates and energies of monoureas and parameters used to calculate the CD spectra. This material is available free of charge via the Internet at http://pubs.acs.org. References and Notes (1) Cheng, R. P. Curr. Opin. Struct. Biol. 2004, 14, 512-520. (2) Cheng, R. P.; Gellman, S. H.; DeGrado, W. F. Chem. ReV. 2001, 101, 3219-3232. (3) Guichard, G. In Pseudopeptides in Drug DeVelopment; Nielsen, P. E., Ed.; Wiley-VCH Verlag: Weinheim, Germany, 2004; pp 33-120. (4) Seebach, D.; Beck, A. K.; Bierbaum, D. J. Chem. BiodiVersity 2004, 1, 1111-1239. (5) Hemmerlin, C.; Marraud, M.; Rognan, D.; Graff, R.; Semetey, V.; Briand, J. P.; Guichard, G. HelV. Chim. Acta 2002, 85, 3692-3711. (6) Semetey, V.; Rognan, D.; Hemmerlin, C.; Graff, R.; Briand, J. P.; Marraud, M.; Guichard, G. Angew. Chem., Int. Ed. 2002, 41, 1893-1895. (7) Violette, A.; Averlant-Petit, M. C.; Semetey, V.; Hemmerlin, C.; Casimir, R.; Graff, R.; Marraud, M.; Briand, J. P.; Rognan, D.; Guichard, G. J. Am. Chem. Soc. 2005, 127, 2156-2164. (8) Burgess, K.; Linthicum, D. S.; Shin, H. W. Angew. Chem., Int. Ed. Engl. 1995, 34, 907-909. (9) Violette, A.; Fournel, S.; Lamour, K.; Chaloin, O.; Frisch, B.; Briand, J. P.; Monteil, H.; Guichard, G. Chem. Biol. 2006, 13, 531-538. (10) Moffitt, W. J. Chem. Phys. 1956, 25, 467-478. (11) Hirst, J. D.; Colella, K.; Gilbert, A. T. B. J. Phys. Chem. B 2003, 107, 11813-11819. (12) Oakley, M. T.; Bulheller, B. M.; Hirst, J. D. Chirality 2006, 18, 340-347. (13) Bayley, P. M.; Nielsen, E. B.; Schellman, J. A. J. Phys. Chem. 1969, 73, 228-243. (14) Goux, W. J.; Hooker, T. M. J. Am. Chem. Soc. 1980, 102, 70807087.
J. Phys. Chem. B, Vol. 111, No. 12, 2007 3279 (15) Daura, X.; Bakowies, D.; Seebach, D.; Fleischhauer, J.; van Gunsteren, W. F.; Kruger, P. Eur. Biophys. J. 2003, 32, 661-670. (16) Glattli, A.; Daura, X.; Seebach, D.; van Gunsteren, W. F. J. Am. Chem. Soc. 2002, 124, 12972-12978. (17) Bode, K. A.; Applequist, J. Macromolecules 1997, 30, 2144-2150. (18) Applequist, J.; Bode, K. A.; Appella, D. H.; Christianson, L. A.; Gellman, S. H. J. Am. Chem. Soc. 1998, 120, 4891-4892. (19) Campbell, B. F.; Clark, L. B. J. Am. Chem. Soc. 1989, 111, 81318136. (20) Xu, S.; Clark, L. B. J. Am. Chem. Soc. 1995, 117, 4379-4386. (21) Otoikhian, A.; Simoyi, R. H.; Petersen, J. L. Chem. Res. Toxicol. 2005, 18, 1167-1177. (22) Elbert, S. T.; Davidson, E. R. Int. J. Quantum Chem. 1974, 8, 857892. (23) Del Bene, J. E.; Worth, G. T.; Marchese, F. T.; Conrad, M. E. Theor. Chim. Acta 1975, 36, 195-206. (24) Ditchfield, R.; Del Bene, J. E.; Pople, J. A. J. Am. Chem. Soc. 1972, 94, 703-&. (25) Sa´nchez de Mera´s, A.; Cuesta, I. G.; Koch, H. Chem. Phys. Lett. 2001, 348, 469-476. (26) Christiansen, O.; Koch, H.; Jørgensen, P. J. Chem. Phys. 1995, 103, 7429-7441. (27) Hirst, J. D.; Persson, B. J. J. Phys. Chem. A 1998, 102, 75197524. (28) Besley, N. A.; Brienne, M. J.; Hirst, J. D. J. Phys. Chem. B 2000, 104, 12371-12377. (29) Kong, J.; White, C. A.; Krylov, A. I.; Sherrill, C. D.; Adamson, R. D.; Furlani, T. R.; Lee, M. S.; Lee, A. M.; Gwaltney, S. R.; Adams, T. R.; Ochsenfeld, C.; Gilbert, A. T. B.; Kedziora, G. S.; Rassolov, V. A.; Maurice, D. R.; Nair, N.; Shao, Y.; Besley, N. A.; Maslen, P. E.; Dombroski, J. P.; Daschel, H.; Zhang, W.; Korambath, P. P.; Baker, J.; Byrd, E. F. C.; Voorhis, T. V.; Oumi, M.; Hirata, S.; Hsu, C.-P.; Ishikawa, N.; Florian, J.; Warshel, A.; Johnson, B. G.; Gill, P. M. W.; Head-Gordon, M.; Pople, J. A. J. Comput. Chem. 2001, 21, 1532-1548. (30) Andersson, K.; Barysz, M.; Bernhardsson, A.; Blomberg, M. R. A.; Carissan, Y.; Cooper, D. L.; Cossi, M.; Fleig, T.; Fu¨lscher, M. P.; Gagliardi, L.; de Graaf, C.; Hess, B. A.; Karlstro¨m, G.; Lindh, R.; Malmqvist, P.-Å.; Neogra´dy, P.; Olsen, J.; Roos, B. O.; Schimmelpfennig, B.; Schu¨tz, M.; Seijo, L.; Serrano-Andre´s, L.; Siegbahn, P. E. M.; Stålring, J.; Thorsteinsson, T.; Veryazov, V.; Wierzbowska, M.; Widmark, P.-O.; MOLCAS, version 5.2; Lund University, 2001. (31) Roos, B. O. Int. J. Quantum Chem. 1980, 17, 175-189. (32) Roos, B. O.; Andersson, K. Chem. Phys. Lett. 1995, 245, 215223. (33) Malmqvist, P.-Å.; Roos, B. O. Chem. Phys. Lett. 1989, 155, 189194. (34) Widmark, P. O.; Malmqvist, P. A.; Roos, B. O. Theor. Chim. Acta 1990, 77, 291-306. (35) Roos, B. O.; Fu¨lscher, M. P.; Malmqvist, P.-Å.; Mercha´n, M.; Serrano-Andre´s, L. In Quantum Mechanical Electronic Structure Calculations with Chemical Accuracy; Langhoff, S. R., Ed.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1995; pp 357-438. (36) Amos, R. D.; Bernhardsson, A.; Berning, A.; Celani, P.; Cooper, D. L.; Deegan, M. J. O.; Dobbyn, A. J.; Eckert, F.; Hampel, C.; Hetzer, G.; Knowles, P. J.; Korona, T.; Lindh, R.; Lloyd, A. W.; McNicholas, S. J.; Manby, F. R.; Meyer, W.; Mura, M. E.; Nicklass, A.; Palmieri, P.; Pitzer, R.; Rauhut, G.; Schu¨tz, M.; Schumann, U.; Stoll, H.; Stone, A. J.; Tarroni, R.; Thorsteinsson, T.; Werner., H.-J.; Molpro, a package of ab initio programs, version 2002.1; University of Birmingham: Birmingham, UK, 2002. (37) Xu, S.; Gantzel, P. K.; Clark, L. B. Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 1994, 50, 1988-1989. (38) Rogers, D. M.; Hirst, J. D. Biochemistry 2004, 43, 11092-11102. (39) Miles, A. J.; Wallace, B. A. Chem. Soc. ReV. 2006, 35, 39-51. (40) Haushalter, K. A.; Lau, J.; Roberts, J. D. J. Am. Chem. Soc. 1996, 118, 8891-8896.
