Removing the C-terminal protecting group enlarges the crystal size: Z–(Gly–Aib)₂–OH·H₂O

The achiral tetra­peptide monohydrate N-(benzyl­oxycarbon­yl)glycyl-α-amino­isobutyrylglycyl-α-amino­isobutyric acid monohydrate, Z–Gly–Aib–Gly–Aib–OH·H₂O (Z is benzyl­oxycarbonyl, Aib is α-amino­isobutyric acid and Gly is glycine) or C₂₀H₂₈N₄O₇·H₂O, exhibits two conformations related by the symmetry operation of an inversion centre. It adopts only one of two possible intra­molecular hydrogen bonds in a type I (and I′) β-turn and forms a maximum of inter­molecular hydrogen bonds partly mediated by water. The space group, the mol­ecular structure and the crystal packing differ from two already described (Gly–Aib)₂ peptides which vary only in the protecting groups. This structure confirms the high structural flexibility of Gly–Aib peptides and points to a strong relationship between inter­molecular hydrogen bonding and crystal quality and size.

Computing details

Data collection: PROTEUM2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: COOT (Emsley et al., 2010) and SwissPDBViewer (Guex & Peitsch, 1997); software used to prepare material for publication: CHEMDRAW (Mills, 2006), ORTEPIII (Burnett & Johnson, 1996), ORTEP-3 (Farrugia, 2012), POVRAY (Povray, 2004) and pyMOL (DeLano, 2002).

N-(Benzoyloxycarbonyl)glycyl-α-aminoisobutyrylglycyl-α-aminoisobutyric acid

Crystal data

C20H28N4O7·H2O	F(000) = 968
Mr = 454.48	Dx = 1.317 Mg m^−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54181 Å
a = 11.071 (2) Å	Cell parameters from 4668 reflections
b = 18.892 (4) Å	θ = 4.7–79.1°
c = 13.115 (3) Å	µ = 0.86 mm^−1
β = 123.29 (3)°	T = 100 K
V = 2292.9 (10) Å^3	Plate, colorless
Z = 4	1 × 0.8 × 0.4 mm

Data collection

Bruker AXS D8 Venture diffractometer	4559 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.072
ω– and φ–scans	θmax = 79.1°, θmin = 4.7°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −14→11
Tmin = 0.741, Tmax = 1.00	k = 0→24
38548 measured reflections	l = 0→16
4668 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.039	All H-atom parameters refined
wR(F^2) = 0.101	w = 1/[σ^2(Fo^2) + (0.050P)^2 + 0.7223P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max = 0.001
4668 reflections	Δρmax = 0.28 e Å^−3
409 parameters	Δρmin = −0.30 e Å^−3
0 restraints

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.91510 (12)	0.60100 (6)	0.66995 (11)	0.0262 (2)
C2	0.82738 (14)	0.59247 (7)	0.54389 (12)	0.0324 (3)
H2	0.7715 (19)	0.6306 (10)	0.4937 (16)	0.043 (4)*
C3	0.81965 (15)	0.52745 (8)	0.49107 (13)	0.0369 (3)
H3	0.759 (2)	0.5219 (9)	0.4043 (18)	0.047 (5)*
C4	0.90377 (15)	0.47116 (7)	0.56388 (13)	0.0345 (3)
H4	0.9015 (19)	0.4268 (10)	0.5279 (17)	0.046 (4)*
C5	0.99308 (13)	0.47969 (7)	0.68879 (13)	0.0316 (3)
H5	1.0532 (18)	0.4418 (9)	0.7376 (16)	0.039 (4)*
C6	0.99697 (12)	0.54395 (7)	0.74216 (11)	0.0281 (2)
H6	1.0589 (16)	0.5506 (8)	0.8303 (15)	0.028 (3)*
C7	0.92781 (12)	0.67156 (7)	0.72778 (12)	0.0311 (3)
H71	0.9808 (19)	0.7048 (9)	0.7087 (16)	0.042 (4)*
H72	0.9747 (17)	0.6669 (8)	0.8173 (16)	0.036 (4)*
O1	0.78399 (8)	0.69950 (4)	0.67513 (7)	0.02663 (18)
C	0.77474 (12)	0.76241 (6)	0.72001 (10)	0.0231 (2)
O	0.87817 (9)	0.79412 (5)	0.80316 (8)	0.0315 (2)
N_1	0.63674 (10)	0.78368 (5)	0.65919 (9)	0.0243 (2)
H_1	0.5738 (18)	0.7590 (9)	0.5988 (16)	0.036 (4)*
CA_1	0.58847 (12)	0.84412 (6)	0.69493 (10)	0.0229 (2)
H1_1	0.6718 (16)	0.8736 (8)	0.7473 (13)	0.024 (3)*
H2_1	0.5197 (16)	0.8696 (8)	0.6260 (13)	0.024 (3)*
C_1	0.52482 (11)	0.82100 (5)	0.76766 (9)	0.0202 (2)
O_1	0.58635 (8)	0.77711 (4)	0.85064 (7)	0.02327 (17)
N_2	0.39913 (10)	0.85166 (5)	0.73553 (8)	0.02074 (19)
H_2	0.3624 (16)	0.8828 (8)	0.6776 (14)	0.027 (3)*
CA_2	0.33258 (11)	0.84259 (6)	0.80569 (10)	0.0218 (2)
CL_2	0.17287 (13)	0.86401 (6)	0.72210 (11)	0.0277 (2)
HL1_2	0.1232 (17)	0.8366 (8)	0.6411 (15)	0.033 (4)*
HL2_2	0.1232 (17)	0.8552 (9)	0.7626 (15)	0.035 (4)*
HL3_2	0.1663 (18)	0.9160 (9)	0.7035 (16)	0.038 (4)*
CG_2	0.41139 (14)	0.88721 (7)	0.92197 (11)	0.0291 (2)
HR1_2	0.5125 (17)	0.8737 (8)	0.9740 (14)	0.030 (4)*
HR2_2	0.3682 (17)	0.8822 (8)	0.9691 (15)	0.035 (4)*
HR3_2	0.4087 (19)	0.9374 (10)	0.8996 (16)	0.042 (4)*
C_2	0.33395 (11)	0.76408 (6)	0.83906 (9)	0.0207 (2)
O_2	0.36516 (8)	0.74711 (4)	0.94202 (7)	0.02521 (18)
N_3	0.28872 (9)	0.71699 (5)	0.74955 (8)	0.02072 (19)
H_3	0.2580 (15)	0.7299 (7)	0.6761 (14)	0.022 (3)*
CA_3	0.27346 (11)	0.64293 (6)	0.76864 (10)	0.0227 (2)
H1_3	0.1930 (17)	0.6240 (8)	0.6920 (14)	0.030 (4)*
H2_3	0.2520 (16)	0.6373 (8)	0.8324 (14)	0.029 (3)*
C_3	0.40426 (11)	0.59681 (5)	0.80928 (9)	0.0203 (2)
O_3	0.39119 (8)	0.53137 (4)	0.81109 (7)	0.02305 (17)
N_4	0.52906 (9)	0.62726 (5)	0.84320 (8)	0.02029 (19)
H_4	0.5363 (16)	0.6733 (9)	0.8423 (13)	0.028 (4)*
CA_4	0.65831 (11)	0.58452 (5)	0.88070 (10)	0.0211 (2)
CL_4	0.79178 (12)	0.63223 (6)	0.95471 (11)	0.0263 (2)
HL1_4	0.7997 (16)	0.6515 (8)	1.0278 (14)	0.028 (3)*
HL2_4	0.8799 (18)	0.6048 (8)	0.9776 (15)	0.036 (4)*
HL3_4	0.7875 (17)	0.6695 (9)	0.9041 (15)	0.034 (4)*
CG_4	0.64769 (13)	0.55466 (6)	0.76802 (11)	0.0269 (2)
HR1_4	0.5609 (18)	0.5230 (8)	0.7211 (15)	0.034 (4)*
HR2_4	0.6407 (16)	0.5929 (8)	0.7164 (15)	0.031 (4)*
HR3_4	0.7331 (17)	0.5274 (8)	0.7913 (14)	0.032 (4)*
C_4	0.67139 (11)	0.52487 (5)	0.96621 (9)	0.0206 (2)
O_4	0.70097 (8)	0.46385 (4)	0.95883 (7)	0.02433 (18)
OH_4	0.65837 (9)	0.54952 (4)	1.05407 (7)	0.02381 (17)
HH_4	0.659 (2)	0.5166 (10)	1.1003 (18)	0.048 (5)*
O_5	1.15983 (11)	0.76722 (7)	1.00148 (9)	0.0449 (3)
H1_5	1.079 (2)	0.7743 (10)	0.9430 (19)	0.050 (5)*
H2_5	1.216 (2)	0.7601 (10)	0.9773 (18)	0.051 (5)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0209 (5)	0.0309 (6)	0.0276 (6)	0.0003 (4)	0.0138 (5)	−0.0011 (4)
C2	0.0322 (6)	0.0347 (6)	0.0261 (6)	0.0083 (5)	0.0134 (5)	0.0035 (5)
C3	0.0390 (7)	0.0408 (7)	0.0281 (7)	0.0036 (5)	0.0166 (6)	−0.0034 (5)
C4	0.0379 (7)	0.0294 (6)	0.0410 (7)	−0.0008 (5)	0.0248 (6)	−0.0034 (5)
C5	0.0272 (5)	0.0277 (6)	0.0396 (7)	0.0004 (4)	0.0182 (5)	0.0075 (5)
C6	0.0216 (5)	0.0347 (6)	0.0260 (6)	−0.0023 (4)	0.0117 (5)	0.0042 (5)
C7	0.0207 (5)	0.0349 (6)	0.0322 (7)	0.0023 (4)	0.0110 (5)	−0.0045 (5)
O1	0.0211 (4)	0.0311 (4)	0.0255 (4)	0.0018 (3)	0.0114 (3)	−0.0041 (3)
C	0.0235 (5)	0.0270 (5)	0.0200 (5)	−0.0004 (4)	0.0128 (4)	0.0010 (4)
O	0.0231 (4)	0.0329 (4)	0.0301 (4)	−0.0009 (3)	0.0092 (4)	−0.0060 (3)
N_1	0.0215 (4)	0.0279 (5)	0.0216 (5)	0.0006 (4)	0.0105 (4)	−0.0037 (4)
CA_1	0.0238 (5)	0.0222 (5)	0.0241 (5)	0.0004 (4)	0.0140 (5)	0.0012 (4)
C_1	0.0208 (5)	0.0189 (5)	0.0188 (5)	−0.0027 (4)	0.0095 (4)	−0.0023 (4)
O_1	0.0214 (4)	0.0218 (4)	0.0224 (4)	0.0001 (3)	0.0094 (3)	0.0037 (3)
N_2	0.0227 (4)	0.0211 (4)	0.0186 (4)	0.0024 (3)	0.0114 (4)	0.0039 (3)
CA_2	0.0241 (5)	0.0228 (5)	0.0211 (5)	0.0026 (4)	0.0140 (4)	0.0018 (4)
CL_2	0.0258 (5)	0.0263 (5)	0.0328 (6)	0.0068 (4)	0.0172 (5)	0.0063 (5)
CG_2	0.0361 (6)	0.0293 (6)	0.0250 (6)	−0.0014 (5)	0.0187 (5)	−0.0031 (5)
C_2	0.0166 (4)	0.0259 (5)	0.0203 (5)	0.0030 (4)	0.0106 (4)	0.0037 (4)
O_2	0.0254 (4)	0.0325 (4)	0.0187 (4)	0.0030 (3)	0.0127 (3)	0.0055 (3)
N_3	0.0205 (4)	0.0221 (4)	0.0183 (4)	0.0012 (3)	0.0098 (4)	0.0034 (3)
CA_3	0.0207 (5)	0.0231 (5)	0.0235 (5)	−0.0016 (4)	0.0116 (4)	0.0016 (4)
C_3	0.0231 (5)	0.0216 (5)	0.0162 (5)	−0.0004 (4)	0.0108 (4)	0.0015 (4)
O_3	0.0266 (4)	0.0198 (4)	0.0225 (4)	−0.0025 (3)	0.0133 (3)	0.0007 (3)
N_4	0.0206 (4)	0.0183 (4)	0.0211 (4)	0.0009 (3)	0.0109 (4)	0.0023 (3)
CA_4	0.0215 (5)	0.0206 (5)	0.0211 (5)	0.0013 (4)	0.0115 (4)	0.0019 (4)
CL_4	0.0221 (5)	0.0245 (5)	0.0295 (6)	−0.0012 (4)	0.0124 (5)	0.0026 (4)
CG_4	0.0322 (6)	0.0286 (5)	0.0243 (5)	0.0026 (5)	0.0183 (5)	0.0019 (5)
C_4	0.0190 (5)	0.0215 (5)	0.0174 (5)	−0.0004 (4)	0.0076 (4)	−0.0005 (4)
O_4	0.0270 (4)	0.0201 (4)	0.0224 (4)	0.0020 (3)	0.0114 (3)	−0.0003 (3)
OH_4	0.0324 (4)	0.0207 (4)	0.0205 (4)	0.0010 (3)	0.0159 (3)	0.0016 (3)
O_5	0.0254 (5)	0.0882 (8)	0.0185 (4)	0.0093 (5)	0.0105 (4)	0.0008 (5)

Geometric parameters (Å, º)

C1—C6	1.3920 (17)	CB_2—HB2_2	0.966 (17)
C1—C2	1.3927 (19)	CB_2—HB3_2	1.004 (17)
C1—C7	1.5016 (17)	CG_2—HG1_2	0.972 (16)
C2—C3	1.3896 (19)	CG_2—HG2_2	0.971 (17)
C2—H2	0.943 (18)	CG_2—HG3_2	0.987 (18)
C3—C4	1.391 (2)	C_2—O_2	1.2383 (13)
C3—H3	0.958 (19)	C_2—N_3	1.3323 (14)
C4—C5	1.382 (2)	N_3—CA_3	1.4474 (14)
C4—H4	0.955 (19)	N_3—H_3	0.862 (15)
C5—C6	1.3902 (18)	CA_3—C_3	1.5143 (15)
C5—H5	0.948 (17)	CA_3—H1_3	0.974 (16)
C6—H6	0.976 (16)	CA_3—H2_3	0.993 (15)
C7—O1	1.4435 (14)	C_3—O_3	1.2466 (13)
C7—H71	0.981 (18)	C_3—N_4	1.3278 (14)
C7—H72	0.994 (17)	N_4—CA_4	1.4727 (13)
O1—C	1.3548 (14)	N_4—H_4	0.874 (16)
C—O	1.2200 (15)	CA_4—CG_4	1.5248 (15)
C—N_1	1.3395 (15)	CA_4—CB_4	1.5374 (16)
N_1—CA_1	1.4436 (14)	CA_4—C_4	1.5395 (15)
N_1—H_1	0.851 (18)	CB_4—HB1_4	0.983 (16)
CA_1—C_1	1.5281 (15)	CB_4—HB2_4	0.995 (16)
CA_1—H1_1	0.968 (15)	CB_4—HB3_4	0.950 (17)
CA_1—H2_1	0.935 (15)	CG_4—HG1_4	1.005 (16)
C_1—O_1	1.2338 (13)	CG_4—HG2_4	0.964 (16)
C_1—N_2	1.3438 (14)	CG_4—HG3_4	0.968 (16)
N_2—CA_2	1.4707 (13)	C_4—O_4	1.2168 (13)
N_2—H_2	0.865 (16)	C_4—OH_4	1.3219 (14)
CA_2—CG_2	1.5287 (16)	OH_4—HH_4	0.87 (2)
CA_2—CB_2	1.5376 (16)	O_5—H1_5	0.81 (2)
CA_2—C_2	1.5441 (15)	O_5—H2_5	0.85 (2)
CB_2—HB1_2	1.029 (16)
C6—C1—C2	119.17 (11)	HB1_2—CB_2—HB2_2	109.8 (13)
C6—C1—C7	119.88 (11)	CA_2—CB_2—HB3_2	109.4 (10)
C2—C1—C7	120.88 (11)	HB1_2—CB_2—HB3_2	108.4 (13)
C3—C2—C1	120.40 (12)	HB2_2—CB_2—HB3_2	108.3 (13)
C3—C2—H2	119.3 (11)	CA_2—CG_2—HG1_2	111.2 (9)
C1—C2—H2	120.3 (11)	CA_2—CG_2—HG2_2	111.7 (10)
C2—C3—C4	119.92 (13)	HG1_2—CG_2—HG2_2	107.9 (13)
C2—C3—H3	120.0 (11)	CA_2—CG_2—HG3_2	109.0 (10)
C4—C3—H3	120.1 (11)	HG1_2—CG_2—HG3_2	107.3 (13)
C5—C4—C3	119.91 (12)	HG2_2—CG_2—HG3_2	109.7 (14)
C5—C4—H4	119.7 (11)	O_2—C_2—N_3	122.21 (10)
C3—C4—H4	120.4 (11)	O_2—C_2—CA_2	120.73 (10)
C4—C5—C6	120.20 (12)	N_3—C_2—CA_2	116.82 (9)
C4—C5—H5	119.6 (10)	C_2—N_3—CA_3	121.07 (9)
C6—C5—H5	120.2 (10)	C_2—N_3—H_3	121.5 (9)
C5—C6—C1	120.33 (12)	CA_3—N_3—H_3	117.1 (9)
C5—C6—H6	121.0 (9)	N_3—CA_3—C_3	115.92 (9)
C1—C6—H6	118.6 (9)	N_3—CA_3—H1_3	107.7 (9)
O1—C7—C1	108.06 (9)	C_3—CA_3—H1_3	108.0 (9)
O1—C7—H71	107.5 (10)	N_3—CA_3—H2_3	110.7 (9)
C1—C7—H71	110.1 (10)	C_3—CA_3—H2_3	105.5 (9)
O1—C7—H72	108.7 (9)	H1_3—CA_3—H2_3	108.9 (12)
C1—C7—H72	111.2 (9)	O_3—C_3—N_4	122.25 (10)
H71—C7—H72	111.1 (14)	O_3—C_3—CA_3	118.61 (9)
C—O1—C7	116.08 (9)	N_4—C_3—CA_3	119.14 (9)
O—C—N_1	126.10 (11)	C_3—N_4—CA_4	121.07 (9)
O—C—O1	124.15 (10)	C_3—N_4—H_4	120.8 (10)
N_1—C—O1	109.75 (10)	CA_4—N_4—H_4	118.1 (10)
C—N_1—CA_1	123.26 (10)	N_4—CA_4—CG_4	109.59 (9)
C—N_1—H_1	118.3 (11)	N_4—CA_4—CB_4	108.08 (9)
CA_1—N_1—H_1	118.4 (11)	CG_4—CA_4—CB_4	111.40 (10)
N_1—CA_1—C_1	110.88 (9)	N_4—CA_4—C_4	109.28 (8)
N_1—CA_1—H1_1	107.9 (8)	CG_4—CA_4—C_4	111.19 (9)
C_1—CA_1—H1_1	107.9 (8)	CB_4—CA_4—C_4	107.20 (9)
N_1—CA_1—H2_1	110.1 (9)	CA_4—CB_4—HB1_4	111.9 (9)
C_1—CA_1—H2_1	110.0 (9)	CA_4—CB_4—HB2_4	109.2 (9)
H1_1—CA_1—H2_1	110.1 (12)	HB1_4—CB_4—HB2_4	110.6 (13)
O_1—C_1—N_2	122.79 (10)	CA_4—CB_4—HB3_4	109.3 (10)
O_1—C_1—CA_1	121.48 (9)	HB1_4—CB_4—HB3_4	110.5 (13)
N_2—C_1—CA_1	115.73 (9)	HB2_4—CB_4—HB3_4	105.2 (13)
C_1—N_2—CA_2	122.80 (9)	CA_4—CG_4—HG1_4	110.6 (9)
C_1—N_2—H_2	118.4 (10)	CA_4—CG_4—HG2_4	109.7 (9)
CA_2—N_2—H_2	118.2 (10)	HG1_4—CG_4—HG2_4	109.6 (13)
N_2—CA_2—CG_2	110.63 (9)	CA_4—CG_4—HG3_4	110.4 (9)
N_2—CA_2—CB_2	107.34 (9)	HG1_4—CG_4—HG3_4	108.5 (13)
CG_2—CA_2—CB_2	111.68 (10)	HG2_4—CG_4—HG3_4	108.0 (13)
N_2—CA_2—C_2	111.03 (8)	O_4—C_4—OH_4	124.47 (10)
CG_2—CA_2—C_2	109.61 (9)	O_4—C_4—CA_4	123.87 (10)
CB_2—CA_2—C_2	106.47 (9)	OH_4—C_4—CA_4	111.43 (9)
CA_2—CB_2—HB1_2	110.9 (9)	C_4—OH_4—HH_4	113.3 (12)
CA_2—CB_2—HB2_2	109.9 (9)	H1_5—O_5—H2_5	109.3 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N_4—H_4···O_1	0.87 (2)	2.026 (16)	2.8910 (13)	171 (1)
N_1—H_1···O_2^i	0.85 (2)	2.090 (18)	2.8441 (18)	148 (2)
N_2—H_2···O_4^ii	0.87 (2)	2.160 (16)	3.0193 (13)	173 (1)
OH_4—HH_4···O_3^iii	0.87 (2)	1.79 (2)	2.6132 (11)	159 (2)
O_5—H1_5···O	0.81 (2)	1.99 (2)	2.8005 (19)	178 (2)
O_5—H2_5···O_2^iv	0.85 (2)	1.96 (2)	2.8046 (14)	173 (2)
N_3—H_3···O_5^v	0.86 (2)	1.921 (16)	2.7591 (16)	163 (1)

Symmetry codes: (i) x, −y+3/2, z−1/2; (ii) −x+1, y+1/2, −z+3/2; (iii) −x+1, −y+1, −z+2; (iv) x+1, y, z; (v) x−1, −y+3/2, z−1/2.