tert-Butoxycarbonylglycyl-dehydroalanyl-glycine methyl ester (systematic name: methyl {2-[(tert-butoxycarbonylamino)acetamido]prop-2-enamido}acetate) (Boc0-Gly1-ΔAla2-Gly3-OMe), C13H21N3O6, has been structurally characterized by single-crystal X-ray diffraction and by density functional theory (DFT) calculations at the B3LYP/6–311+G** level. The peptide chain in both the solid-state and calculated structures adopts neither β nor γ turns. All amino acid residues in the tripeptide sequence are linked trans to each other. The bond lengths and valence angles of the amino acid units in the crystal structure and gas phase are comparable. However, the conformation of the third glycyl residue (Gly3) is different in the crystalline state and in the gas phase. It is stabilized in the calculated structure by an additional intramolecular short contact between Gly3 NH and methyl ester COMe groups.
Supporting information
CCDC reference: 604222
The title compound was synthesized by the reaction of Boc-Gly-ΔAla (after
activation with N,N'-dicyclohexylcarbodiimide and
1-hydroxybenzotriazole) with Gly-OMe at room temperature for 24 h (Makowski
et al., 1986). Crystals of (I) suitable for X-ray crystal structure
analysis were grown from a CHCl3–MeOH (1:1)–hexane [Please give ratio of
all three components] solution.
The geometry of (I) in the crystal state was used as the starting structure for
full optimization using standard density functional theory (DFT) employing the
B3LYP hybrid function (Becke, 1988; Lee et al., 1988; Becke, 1993) at
the 6–311+G** level of theory, with no imaginary frequencies. The
calculations were carried out using GAUSSIAN03 (Frisch et al.,
2004). H atoms were located in a difference Fourier map and refined freely;
refined C—H and N—H distances are in the ranges ?–? Å and ?–? Å,
respectively [Please complete].
Data collection: CrysAlis CCD (Oxford Diffraction, 2002); cell refinement: CrysAlis RED (Oxford Diffraction, 2002); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 1990); software used to prepare material for publication: SHELXL97.
tert-Butoxycarbonylglycyl-dehydroalanyl-glycine methyl ester
top
Crystal data top
C13H21N3O6 | Z = 2 |
Mr = 315.33 | F(000) = 336 |
Triclinic, P1 | Dx = 1.370 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 8.6343 (14) Å | Cell parameters from 7435 reflections |
b = 8.7713 (14) Å | θ = 3.4–26.0° |
c = 11.2379 (15) Å | µ = 0.11 mm−1 |
α = 110.158 (13)° | T = 100 K |
β = 98.428 (12)° | Cube, colourless |
γ = 100.631 (14)° | 0.51 × 0.48 × 0.46 mm |
V = 764.6 (2) Å3 | |
Data collection top
Oxford Xcalibur diffractometer | 2676 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.022 |
Graphite monochromator | θmax = 26.0°, θmin = 3.4° |
Detector resolution: 1024x1024 with blocks 2x2 pixels mm-1 | h = −6→10 |
ω scans | k = −10→10 |
7435 measured reflections | l = −13→13 |
3000 independent reflections | |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.031 | All H-atom parameters refined |
wR(F2) = 0.082 | w = 1/[σ2(Fo2) + (0.0442P)2 + 0.1565P] where P = (Fo2 + 2Fc2)/3 |
S = 1.08 | (Δ/σ)max < 0.001 |
3000 reflections | Δρmax = 0.23 e Å−3 |
284 parameters | Δρmin = −0.21 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.021 (3) |
Crystal data top
C13H21N3O6 | γ = 100.631 (14)° |
Mr = 315.33 | V = 764.6 (2) Å3 |
Triclinic, P1 | Z = 2 |
a = 8.6343 (14) Å | Mo Kα radiation |
b = 8.7713 (14) Å | µ = 0.11 mm−1 |
c = 11.2379 (15) Å | T = 100 K |
α = 110.158 (13)° | 0.51 × 0.48 × 0.46 mm |
β = 98.428 (12)° | |
Data collection top
Oxford Xcalibur diffractometer | 2676 reflections with I > 2σ(I) |
7435 measured reflections | Rint = 0.022 |
3000 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.031 | 0 restraints |
wR(F2) = 0.082 | All H-atom parameters refined |
S = 1.08 | Δρmax = 0.23 e Å−3 |
3000 reflections | Δρmin = −0.21 e Å−3 |
284 parameters | |
Special details top
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell e.s.d.'s are taken
into account individually in the estimation of e.s.d.'s in distances, angles
and torsion angles; correlations between e.s.d.'s in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s.
planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor
wR and goodness of fit S are based on F2, conventional
R-factors R are based on F, with F set to zero for
negative F2. The threshold expression of F2 >
σ(F2) is used only for calculating R-factors(gt) etc.
and is not relevant to the choice of reflections for refinement.
R-factors based on F2 are statistically about twice as large
as those based on F, and R- factors based on ALL data will be
even larger. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
C1 | 0.63869 (16) | 1.12041 (16) | 0.38517 (12) | 0.0271 (3) | |
C2 | 0.75416 (15) | 1.04655 (17) | 0.18817 (15) | 0.0289 (3) | |
C3 | 0.45946 (15) | 1.02527 (16) | 0.16322 (12) | 0.0233 (3) | |
C4 | 0.60829 (13) | 1.01074 (14) | 0.24325 (11) | 0.0195 (2) | |
O5 | 0.59474 (9) | 0.83523 (10) | 0.22956 (8) | 0.01989 (19) | |
C6 | 0.47197 (12) | 0.74786 (14) | 0.25705 (10) | 0.0163 (2) | |
O7 | 0.35847 (9) | 0.79777 (10) | 0.29474 (7) | 0.01881 (18) | |
N8 | 0.49033 (11) | 0.59243 (12) | 0.23623 (9) | 0.0175 (2) | |
C9 | 0.38542 (13) | 0.47449 (14) | 0.26990 (11) | 0.0184 (2) | |
C10 | 0.23509 (13) | 0.36330 (13) | 0.16559 (11) | 0.0171 (2) | |
O11 | 0.14065 (10) | 0.25943 (10) | 0.18581 (8) | 0.0233 (2) | |
N12 | 0.21658 (11) | 0.39351 (12) | 0.05533 (9) | 0.0173 (2) | |
C13 | 0.08327 (13) | 0.32448 (14) | −0.05007 (10) | 0.0174 (2) | |
C14 | −0.04576 (14) | 0.20692 (16) | −0.06441 (12) | 0.0254 (3) | |
C15 | 0.10913 (12) | 0.40105 (13) | −0.14789 (10) | 0.0161 (2) | |
O16 | 0.24164 (9) | 0.49336 (10) | −0.13541 (7) | 0.01866 (19) | |
N17 | −0.01318 (11) | 0.36630 (12) | −0.24765 (9) | 0.0176 (2) | |
C18 | 0.01102 (14) | 0.44023 (14) | −0.34205 (11) | 0.0193 (2) | |
C19 | 0.12270 (13) | 0.37226 (14) | −0.42596 (10) | 0.0176 (2) | |
O20 | 0.22079 (10) | 0.45815 (11) | −0.45697 (8) | 0.0258 (2) | |
O21 | 0.09356 (10) | 0.20685 (10) | −0.46601 (8) | 0.02215 (19) | |
C22 | 0.18710 (17) | 0.13081 (17) | −0.55562 (13) | 0.0277 (3) | |
H1A | 0.5519 (17) | 1.0885 (17) | 0.4240 (14) | 0.024 (3)* | |
H1B | 0.6533 (16) | 1.2382 (19) | 0.3924 (14) | 0.028 (4)* | |
H1C | 0.7411 (19) | 1.1103 (19) | 0.4333 (15) | 0.035 (4)* | |
H2A | 0.7741 (18) | 1.162 (2) | 0.1904 (15) | 0.033 (4)* | |
H2B | 0.7367 (19) | 0.967 (2) | 0.0967 (17) | 0.039 (4)* | |
H2C | 0.8465 (19) | 1.0376 (19) | 0.2414 (15) | 0.033 (4)* | |
H3A | 0.3694 (17) | 1.0332 (18) | 0.2073 (14) | 0.027 (3)* | |
H3B | 0.4895 (17) | 1.130 (2) | 0.1476 (14) | 0.031 (4)* | |
H3C | 0.4217 (17) | 0.930 (2) | 0.0809 (15) | 0.030 (4)* | |
H8 | 0.5779 (18) | 0.5710 (18) | 0.2120 (14) | 0.026 (3)* | |
H9A | 0.3497 (16) | 0.5323 (17) | 0.3446 (14) | 0.021 (3)* | |
H9B | 0.4463 (16) | 0.4000 (17) | 0.2900 (13) | 0.022 (3)* | |
H12 | 0.2932 (16) | 0.4678 (17) | 0.0479 (13) | 0.019 (3)* | |
H14A | −0.1327 (18) | 0.1679 (19) | −0.1421 (15) | 0.031 (4)* | |
H14B | −0.0581 (18) | 0.1575 (19) | −0.0008 (15) | 0.033 (4)* | |
H17 | −0.1094 (18) | 0.3104 (18) | −0.2529 (14) | 0.026 (4)* | |
H18A | 0.0535 (16) | 0.5606 (18) | −0.3003 (13) | 0.021 (3)* | |
H18B | −0.0929 (17) | 0.4159 (18) | −0.3998 (14) | 0.027 (3)* | |
H22A | 0.1760 (17) | 0.1631 (18) | −0.6300 (15) | 0.030 (4)* | |
H22B | 0.1436 (19) | 0.010 (2) | −0.5822 (16) | 0.039 (4)* | |
H22C | 0.302 (2) | 0.167 (2) | −0.5113 (15) | 0.037 (4)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0311 (7) | 0.0204 (6) | 0.0241 (6) | 0.0007 (5) | 0.0008 (5) | 0.0068 (5) |
C2 | 0.0217 (6) | 0.0264 (7) | 0.0420 (8) | 0.0027 (5) | 0.0115 (5) | 0.0173 (6) |
C3 | 0.0230 (6) | 0.0235 (6) | 0.0239 (6) | 0.0046 (5) | 0.0044 (5) | 0.0107 (5) |
C4 | 0.0186 (5) | 0.0148 (5) | 0.0239 (6) | 0.0015 (4) | 0.0043 (4) | 0.0076 (4) |
O5 | 0.0166 (4) | 0.0161 (4) | 0.0274 (4) | 0.0029 (3) | 0.0073 (3) | 0.0085 (3) |
C6 | 0.0140 (5) | 0.0181 (5) | 0.0132 (5) | 0.0006 (4) | −0.0002 (4) | 0.0048 (4) |
O7 | 0.0163 (4) | 0.0204 (4) | 0.0198 (4) | 0.0047 (3) | 0.0054 (3) | 0.0073 (3) |
N8 | 0.0141 (4) | 0.0178 (5) | 0.0206 (5) | 0.0036 (4) | 0.0051 (4) | 0.0071 (4) |
C9 | 0.0187 (5) | 0.0178 (5) | 0.0192 (6) | 0.0038 (4) | 0.0041 (4) | 0.0085 (4) |
C10 | 0.0176 (5) | 0.0161 (5) | 0.0192 (5) | 0.0063 (4) | 0.0066 (4) | 0.0067 (4) |
O11 | 0.0229 (4) | 0.0232 (4) | 0.0239 (4) | 0.0003 (3) | 0.0047 (3) | 0.0122 (4) |
N12 | 0.0144 (4) | 0.0188 (5) | 0.0172 (5) | 0.0006 (4) | 0.0040 (3) | 0.0069 (4) |
C13 | 0.0164 (5) | 0.0190 (5) | 0.0159 (5) | 0.0052 (4) | 0.0048 (4) | 0.0048 (4) |
C14 | 0.0196 (6) | 0.0313 (7) | 0.0230 (6) | −0.0017 (5) | 0.0016 (5) | 0.0130 (5) |
C15 | 0.0158 (5) | 0.0154 (5) | 0.0167 (5) | 0.0059 (4) | 0.0071 (4) | 0.0035 (4) |
O16 | 0.0155 (4) | 0.0203 (4) | 0.0202 (4) | 0.0034 (3) | 0.0057 (3) | 0.0078 (3) |
N17 | 0.0148 (5) | 0.0206 (5) | 0.0173 (5) | 0.0031 (4) | 0.0047 (3) | 0.0073 (4) |
C18 | 0.0197 (5) | 0.0187 (6) | 0.0202 (6) | 0.0054 (4) | 0.0035 (4) | 0.0084 (5) |
C19 | 0.0184 (5) | 0.0194 (5) | 0.0149 (5) | 0.0031 (4) | −0.0003 (4) | 0.0088 (4) |
O20 | 0.0270 (4) | 0.0252 (4) | 0.0266 (5) | 0.0018 (3) | 0.0089 (3) | 0.0130 (4) |
O21 | 0.0289 (4) | 0.0187 (4) | 0.0229 (4) | 0.0078 (3) | 0.0121 (3) | 0.0094 (3) |
C22 | 0.0365 (7) | 0.0291 (7) | 0.0250 (6) | 0.0161 (6) | 0.0151 (5) | 0.0120 (5) |
Geometric parameters (Å, º) top
C1—C4 | 1.5048 (17) | C10—O11 | 1.2122 (13) |
C1—H1A | 0.966 (14) | C10—N12 | 1.3473 (14) |
C1—H1B | 0.990 (15) | N12—C13 | 1.3940 (14) |
C1—H1C | 1.002 (16) | N12—H12 | 0.874 (14) |
C2—C4 | 1.5115 (16) | C13—C14 | 1.3188 (16) |
C2—H2A | 0.984 (16) | C13—C15 | 1.4950 (15) |
C2—H2B | 0.995 (17) | C14—H14A | 0.975 (15) |
C2—H2C | 0.956 (16) | C14—H14B | 0.964 (16) |
C3—C4 | 1.5090 (16) | C15—O16 | 1.2317 (13) |
C3—H3A | 0.982 (14) | C15—N17 | 1.3281 (14) |
C3—H3B | 0.989 (16) | N17—C18 | 1.4417 (14) |
C3—H3C | 0.969 (16) | N17—H17 | 0.866 (15) |
C4—O5 | 1.4739 (13) | C18—C19 | 1.5052 (16) |
O5—C6 | 1.3288 (13) | C18—H18A | 0.967 (14) |
C6—O7 | 1.2181 (13) | C18—H18B | 0.967 (15) |
C6—N8 | 1.3450 (15) | C19—O20 | 1.1993 (14) |
N8—C9 | 1.4347 (14) | C19—O21 | 1.3240 (14) |
N8—H8 | 0.871 (15) | O21—C22 | 1.4441 (14) |
C9—C10 | 1.5196 (16) | C22—H22A | 0.968 (16) |
C9—H9A | 0.947 (14) | C22—H22B | 0.981 (17) |
C9—H9B | 0.973 (14) | C22—H22C | 0.984 (16) |
| | | |
C4—C1—H1A | 112.0 (8) | H9A—C9—H9B | 108.6 (11) |
C4—C1—H1B | 107.8 (8) | O11—C10—N12 | 124.81 (10) |
H1A—C1—H1B | 111.2 (12) | O11—C10—C9 | 120.22 (10) |
C4—C1—H1C | 109.3 (9) | N12—C10—C9 | 114.95 (9) |
H1A—C1—H1C | 108.1 (12) | C10—N12—C13 | 127.46 (10) |
H1B—C1—H1C | 108.4 (12) | C10—N12—H12 | 118.5 (9) |
C4—C2—H2A | 109.5 (9) | C13—N12—H12 | 114.0 (9) |
C4—C2—H2B | 110.9 (9) | C14—C13—N12 | 125.94 (11) |
H2A—C2—H2B | 109.1 (13) | C14—C13—C15 | 124.30 (10) |
C4—C2—H2C | 108.6 (9) | N12—C13—C15 | 109.74 (9) |
H2A—C2—H2C | 108.5 (13) | C13—C14—H14A | 119.2 (9) |
H2B—C2—H2C | 110.2 (13) | C13—C14—H14B | 122.6 (9) |
C4—C3—H3A | 113.4 (8) | H14A—C14—H14B | 118.2 (12) |
C4—C3—H3B | 107.4 (8) | O16—C15—N17 | 121.43 (10) |
H3A—C3—H3B | 107.3 (12) | O16—C15—C13 | 120.12 (10) |
C4—C3—H3C | 110.8 (9) | N17—C15—C13 | 118.45 (9) |
H3A—C3—H3C | 108.1 (12) | C15—N17—C18 | 118.66 (9) |
H3B—C3—H3C | 109.8 (12) | C15—N17—H17 | 122.0 (9) |
O5—C4—C1 | 109.25 (9) | C18—N17—H17 | 119.0 (9) |
O5—C4—C3 | 110.65 (9) | N17—C18—C19 | 114.34 (9) |
C1—C4—C3 | 112.36 (10) | N17—C18—H18A | 111.1 (8) |
O5—C4—C2 | 102.05 (9) | C19—C18—H18A | 107.7 (8) |
C1—C4—C2 | 111.44 (10) | N17—C18—H18B | 107.8 (8) |
C3—C4—C2 | 110.61 (10) | C19—C18—H18B | 106.9 (9) |
C6—O5—C4 | 122.19 (8) | H18A—C18—H18B | 108.9 (12) |
O7—C6—O5 | 126.23 (10) | O20—C19—O21 | 124.61 (10) |
O7—C6—N8 | 124.15 (10) | O20—C19—C18 | 123.44 (10) |
O5—C6—N8 | 109.62 (9) | O21—C19—C18 | 111.86 (9) |
C6—N8—C9 | 122.44 (9) | C19—O21—C22 | 115.14 (9) |
C6—N8—H8 | 116.6 (9) | O21—C22—H22A | 111.5 (9) |
C9—N8—H8 | 120.3 (9) | O21—C22—H22B | 104.8 (10) |
N8—C9—C10 | 116.01 (9) | H22A—C22—H22B | 111.1 (13) |
N8—C9—H9A | 109.8 (8) | O21—C22—H22C | 109.7 (9) |
C10—C9—H9A | 106.9 (8) | H22A—C22—H22C | 108.1 (12) |
N8—C9—H9B | 108.5 (8) | H22B—C22—H22C | 111.6 (13) |
C10—C9—H9B | 106.8 (8) | | |
| | | |
C1—C4—O5—C6 | 67.61 (12) | C10—N12—C13—C15 | 176.28 (10) |
C3—C4—O5—C6 | −56.60 (13) | C14—C13—C15—O16 | −170.24 (11) |
C2—C4—O5—C6 | −174.33 (10) | N12—C13—C15—O16 | 8.49 (13) |
C4—O5—C6—O7 | 0.50 (16) | C14—C13—C15—N17 | 9.42 (16) |
C4—O5—C6—N8 | −179.88 (9) | N12—C13—C15—N17 | −171.84 (9) |
O7—C6—N8—C9 | −6.82 (16) | O16—C15—N17—C18 | −0.52 (15) |
O5—C6—N8—C9 | 173.55 (9) | C13—C15—N17—C18 | 179.82 (9) |
C6—N8—C9—C10 | 88.99 (13) | C15—N17—C18—C19 | 69.74 (13) |
N8—C9—C10—O11 | 179.49 (10) | N17—C18—C19—O20 | −140.05 (11) |
N8—C9—C10—N12 | −2.04 (14) | N17—C18—C19—O21 | 43.13 (13) |
O11—C10—N12—C13 | 5.83 (18) | O20—C19—O21—C22 | −1.55 (16) |
C9—C10—N12—C13 | −172.56 (10) | C18—C19—O21—C22 | 175.23 (9) |
C10—N12—C13—C14 | −5.01 (19) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N8—H8···O16i | 0.87 (2) | 1.97 (2) | 2.834 (1) | 173 (1) |
N17—H17···O7ii | 0.87 (2) | 2.10 (2) | 2.944 (1) | 167 (1) |
C1—H1B···O20iii | 0.99 (2) | 2.48 (2) | 3.434 (2) | 161 (1) |
C14—H14A···O7ii | 0.98 (2) | 2.54 (2) | 3.439 (2) | 154 (1) |
C18—H18A···O11ii | 0.97 (1) | 2.68 (1) | 3.240 (2) | 117.6 (9) |
C18—H18B···O20iv | 0.97 (2) | 2.49 (2) | 3.259 (1) | 137 (1) |
C22—H22A···O11v | 0.97 (2) | 2.49 (2) | 3.459 (2) | 177 (1) |
Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x, −y+1, −z; (iii) −x+1, −y+2, −z; (iv) −x, −y+1, −z−1; (v) x, y, z−1. |
Experimental details
Crystal data |
Chemical formula | C13H21N3O6 |
Mr | 315.33 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 100 |
a, b, c (Å) | 8.6343 (14), 8.7713 (14), 11.2379 (15) |
α, β, γ (°) | 110.158 (13), 98.428 (12), 100.631 (14) |
V (Å3) | 764.6 (2) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.51 × 0.48 × 0.46 |
|
Data collection |
Diffractometer | Oxford Xcalibur diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7435, 3000, 2676 |
Rint | 0.022 |
(sin θ/λ)max (Å−1) | 0.617 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.031, 0.082, 1.08 |
No. of reflections | 3000 |
No. of parameters | 284 |
H-atom treatment | All H-atom parameters refined |
Δρmax, Δρmin (e Å−3) | 0.23, −0.21 |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N8—H8···O16i | 0.87 (2) | 1.97 (2) | 2.834 (1) | 173 (1) |
N17—H17···O7ii | 0.87 (2) | 2.10 (2) | 2.944 (1) | 167 (1) |
C1—H1B···O20iii | 0.99 (2) | 2.48 (2) | 3.434 (2) | 161 (1) |
C14—H14A···O7ii | 0.98 (2) | 2.54 (2) | 3.439 (2) | 154 (1) |
C18—H18A···O11ii | 0.97 (1) | 2.68 (1) | 3.240 (2) | 117.6 (9) |
C18—H18B···O20iv | 0.97 (2) | 2.49 (2) | 3.259 (1) | 137 (1) |
C22—H22A···O11v | 0.97 (2) | 2.49 (2) | 3.459 (2) | 177 (1) |
Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x, −y+1, −z; (iii) −x+1, −y+2, −z; (iv) −x, −y+1, −z−1; (v) x, y, z−1. |
Comparison of selected geometric data for (I) (Å, °) from X-ray and
calculated (DFT) data topDistance or Angle | X-ray | DFT |
C6-N8 | 1.345 (2) | 1.377 |
N8-C9 | 1.435 (1) | 1.449 |
C9-C10 | 1.520 (2) | 1.535 |
C10-O11 | 1.212 (1) | 1.219 |
C10-N12 | 1.347 (1) | 1.367 |
N12-C13 | 1.394 (1) | 1.398 |
C13-C14 | 1.319 (2) | 1.341 |
C13-C15 | 1.495 (2) | 1.513 |
C15-O16 | 1.232 (1) | 1.228 |
C15-N17 | 1.328 (1) | 1.355 |
N17-C18 | 1.442 (1) | 1.451 |
O11-C10-N12 | 124.8 (1) | 124.88 |
O11-C10-C9 | 120.2 (1) | 119.98 |
N12-C10-C9 | 114.95 (9) | 115.14 |
C10-N12-C13 | 127.5 (1) | 128.05 |
C14-C13-N12 | 125.9 (1) | 125.97 |
C14-C13-C15 | 124.3 (1) | 124.30 |
N12-C13-C15 | 109.74 (9) | 109.70 |
O16-C15-N17 | 121.4 (1) | 122.17 |
O16-C15-C13 | 120.1 (1) | 120.26 |
N17-C15-C13 | 118.45 (9) | 117.57 |
C15-N17-C18 | 118.66 (9) | 120.57 |
N17-C18-C19 | 114.34 (9) | 113.79 |
O5-C6-N8-C9 ω0 | 173.55 (9) | 169.68 |
C6-N8-C9-C10 ϕ1 | 89.0 (1) | 116.90 |
N8-C9-C10-N12 ψ1 | -2.0 (1) | -14.38 |
C9-C10-N12-C13 ω1 | -172.6 (1) | -179.52 |
C10-N12-C13-C15 ϕ2 | 176.3 (1) | 179.97 |
N12-C13-C15-N17 ψ2 | -171.84 (9) | -166.48 |
O16-C15-N17-C18 | -0.5 (2) | 0.09 |
C13-C15-N17-C18 ω2 | 179.82 (9) | 179.78 |
C15-N17-C18-C19 ϕ3 | 69.7 (1) | 176.84 |
N17-C18-C19-O20 | -140.0 (1) | -176.61 |
N17-C18-C19-O21 ψ3 | 43.1 (1) | 3.88 |
Intramolecular hydrogen-bonding and short-contact geometry in (I) (Å, °)
*X-ray, **DFT. topD-H···A | D-H | H···A | D···A | D-H···A |
N12-H12···O16* | 0.87 (1) | 2.14 (1) | 2.602 (1) | 112 (1) |
** | 1.02 | 2.12 | 2.63 | 109 |
N12-H12···N8* | 0.87 (1) | 2.29 (1) | 2.718 (1) | 110 (1) |
** | 1.02 | 2.30 | 2.73 | 108 |
C1-H1A···O7* | 0.97 (1) | 2.56 (1) | 3.109 (2) | 116 (1) |
** | 1.09 | 2.46 | 3.052 | 113 |
C3-H3A···O7* | 0.98 (1) | 2.57 (1) | 2.949 (2) | 103.1 (9) |
** | 1.09 | 2.46 | 3.049 | 113 |
C14-H14B···O11* | 0.96 (2) | 2.29 (2) | 2.867 (2) | 118 (1) |
** | 1.08 | 1.26 | 2.910 | 117 |
N17-H17···O21** | 1.01 | 2.19 | 2.628 | 105 |
The α,β-dehydroamino acids in peptides have been found to be responsible for the formation of derivatives of natural peptides with interesting biological activities (Jain & Chauhan, 1996). This is mainly based on the presence of a Cα═Cβ double bond, which gives not only a specific chemical property, but also an inherent conformational preference. Therefore, α,β-dehydroamino acid residues attract much interest as a significant element in secondary structure design (helices, sheets and turns) in peptides. Apart from the presence of the Cα═Cβ bond, which introduces steric repulsions, an important role is also played by intramolecular N—H···O, N—H···N and C—H···O hydrogen bonds and N—H···π-electron cross conjugation (Sigh & Kaur, 1997; Venkatachalam, 1968; Perczel et al., 1996; Vass et al., 2003).
The title methyl ester, Boc0–Gly1–ΔAla2–Gly3–OMe, (I), represents an example of a peptide with a rigid central amino acid (ΔAla) placed between two flexible glycine residues. Dehydroalanine (ΔAla) is the simplest and most widespread α,β-dehydroamino acid. The insertion of such a small molecule into a peptide chain may significantly change its properties, e.g. the insertion of a ΔAla residue into the chains of the tripeptides Gly-ΔAla-Gly and Gly-ΔAla-Phe or the tetrapeptides Gly-ΔAla-Phe-Gly and Gly-Gly-ΔAla-Phe has an influence on the binding abilities of these peptide ligands towards copper(II) ions (Świ\,atek-Kozłowska et al., 2000). Another example is the Gly-ΔAla-Gly-Phe-pNA tetrapeptide, which acts as a substrate of dipeptidyl-peptidase (cathepsin C), representing comparable activity to their classical counterparts (Makowski et al., 2001).
ΔAla adopts an almost planar conformation, with a trans orientation for the ϕ and ψ torsion angles, and induces an inverse γ turn in the preceding residue. Similar effects were observed for linear dehydroalanine-containing peptides in solution or in the crystal state. It seems that dehydroalanine exerts a powerful conformational influence independently of other constraints (Palmer et al., 1992). A number of theoretical calculations have been devoted to the conformational preferences of ΔAla (e.g. Crisma et al., 1999; Füzéry & Csizmadia, 2000; Rzeszotarska et al., 2002; Siodłak et al., 2004; Broda et al., 2005). All these studies provide evidence that the fully extended conformation (C5) is preferred by the ΔAla residue, with the ϕ, ψ and ω backbone torsion angles very close to the trans orientation. This structure is stabilized by two types of intramolecular hydrogen bonds: Ni—H···Oi═Ci, with a five-membered ring C5 form, and CBi+1—H···Oi═Ci, giving rise to a six-membered ring system. The conformational map calculated for Ac-ΔAla-NHMe reveals four minima located at values of the ϕ and ψ angles of around 180 or 0°. The lowest-energy conformer presents the fully extended structure, with ϕ and ψ torsion angles of 180 and 169°, respectively.
The conformation of (I) in the crystal structure, with the atom-numbering scheme, is shown in Fig. 1. This conformation is stabilized by both inter- and intramolecular hydrogen bonds and short contacts, and details of these are given in Tables 1 and 3. The similar tripeptide Boc-Gly-ΔPhe-Gly-OMe forms a type IIβ turn, with an intramolecular N—H···O hydrogen bond between the third and first peptide units. The C1α···C3α distance is 5.387 (4) Å (Główka, 1988). The analogous distance in (I) is 7.038 (2) Å, which is insufficient for considering the secondary structure of (I) as a β turn. Additionally, the 1←4 (C10) and 1←3 (C7) intramolecular hydrogen bonds, which are characteristic for β and γ turns, respectively, are not present.
The calculated conformation of (I) is shown in Fig. 2. This is the lowest-energy conformation of this compound in the gas phase. On the basis of the hydrogen-bonding backbone and the values of the ϕ and ψ torsion angles, the conformation of (I) in the gas phase could not be assigned to either β or γ turns. Table 2 lists the bond lengths and angles of the title compound in the crystal structure and calculated by the DFT method. All bond distances and valence angles are in good agreement with those observed in other peptides containing the ΔAla and Gly residues (Crisma et al., 1999; Rzeszotarska et al., 2002; Ajo et al., 1979; Palmer et al., 1992; Padmanabhan et al., 1992; Piazzesi et al., 1993). There are no significant differences between the bond lengths and angles of this tripeptide in the solid state and in the calculated structure; the differences do not exceed 0.04 Å for bond distances and 2° for bond angles.
In both the solid state and gas phase, the Gly1-ΔAla2 fragment of (I) adopts the fully extended conformation, with ϕ and ψ angles of around 180 and -170°, respectively. The planarity of this fragment is stabilized by intramolecular C14—H14B···O11, N12—H12···O16 and N12—H12···N8 hydrogen bonds and short contacts. Additionally, the co-planarity of the Gly1-ΔAla2 residue favours π-conjugation of the C13═C14 double bond with neighbouring amide bonds.
The differences between both the solid state and the gas phase of (I) become clearly visible when the torsion angles and intermolecular hydrogen bonds are considered. There are two places in the structure where these differences are particularly marked. One of these is the Gly1 residue. The value of ϕ1 which characterizes this residue increases from 89.0 (1)° in the crystal structure to 116° in the gas phase. More significant differences in conformation are observed in the Gly3 residue. The value of the C15—N17—C18—C19 torsion angle which characterizes this residue in the crystal structure is 69.7 (1)°, while in the gas phase this angle increases by more than 100° to 176.84°, due to the fact that the Gly3 and OMe residues become nearly coplanar. This conformational change is stabilized by an intramolecular N17—H17···O21 short contact (Table 3) observed only in the calculated structure.
Because of many competitive intermolecular hydrogen bonds, in the crystal structure of (I) there is a relatively large rotation of the N17—C18 bond (over 100°) and a slightly lower rotation of the C18—C19 bond. A relatively strong N17—H17···O7ii hydrogen bond (which causes the molecules to arrange in a head-to-tail fashion) is present in the crystal structure of (I), as well as two others, C18—H18A···O11ii and C18—H18B···O20iv. Apart from these hydrogen bonds, there are also other intermolecular interactions, but only these hydrogen bonds cause the non-planarity of this residue in the crystal structure.
In similar compounds which contain the Gly-OMe residue, such as ethyl (4-bromo-1H-pyrrole-2-carboxamido)acetate (Zeng, 2005), N-(tert-butoxycarbonylglycyl-(Z)-α,β-dehydrophenylalanylglycyl-(E)-α,β- dehydrophenylalanyl)glycine methyl ester dihydrate (Makowski et al., 2006), 4,5-bis[(ethoxyglycyl)carbonyl]-1H-imidazole and 4-ethoxycarbonyl-5-([(methoxyglycyl)carbonyl]-1H-imidazole (Baures et al., 2003) and tert-butoxycarbonyl-glycyl-dehydrophenylalanyl-glycine methyl ester (Główka, 1988), the analogous torsion angles are -66.67, 135.24, 94.62, -92.24 and 71.67°, respectively. This indicates that this fragment is usually twisted in the crystal structure.
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