Download citation
Download citation
link to html
One of the amino H atoms of L-phenyl­alanyl-L-valine, C14H20N2O3, participates in a rare secondary interaction in being accepted by the aromatic ring of the phenyl­alanine side chain. The phenyl group is also a donor in a weak hydrogen bond to the peptide carbonyl group.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270100012762/jz1429sup1.cif
Contains datablocks L-Phe-L-Val, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270100012762/jz1429L-Phe-L-Valsup2.hkl
Contains datablock L-Phe-L-Val

CCDC reference: 156179

Comment top

Dipeptides with two hydrophobic residues (L-Ala, L-Val, L-Leu, L-Ile, L-Met, L-Phe) have a high propensity to form cocrystals with organic solvent molecules (Görbitz, 1999a, and references therein). The resulting structures are characterized by being divided into hydrophobic layers with peptide side chains, and hydrophilic layers with two head-to-tail hydrogen-bonded chains involving the N-terminal amino groups and the C-terminal carboxylate groups. The third amino H atom is accepted by the solvent molecule, which is embedded in the hydrophobic layer. Only one example has been found of a layered hydrophobic dipeptide structure completely devoid of solvent molecules. This is the structure of L-Met-L-Met (Stenkamp & Jensen, 1975), for which we previously stated that `the last amino H atom is not used for hydrogen bonding' (Görbitz & Gundersen, 1996a). A closer inspection, however, reveals that an N—H···S interaction is in fact present [d(H···S) = 2.79 (3), or 2.656 Å with the N—H distance normalized to 1.030 Å], which means that the methionine side chain is a weak hydrogen-bond acceptor.

Unlike most other hydrophobic dipeptides L-Phe-L-Val crystallizes as thin plates. This property sets it apart from the hexagonal needles of L-Ala-L-Val, L-Val-L-Val (Görbitz, 2001) and L-Leu-L-Val.3/4H2O (Görbitz & Gundersen, 1996b), and also from the very hydrophobic needles of the L-Leu/Phe-L-Leu/Phe series, which all form columnar structures (Görbitz, 2001). The structure of the title compound is clearly different in being divided into layers.

The hydrogen-bonding pattern involves two parallel head-to-tail chains, one for each carboxylate oxygen atom, Fig. 2. Within each chain alternate peptide molecules are related by a twofold screw axis. The third and last classical hydrogen bond also generates a chain, perpendicular to the first two, by connecting the peptide bond >N—H with the anti lone pair of O3. The resulting pleated pattern is shared with five other dipeptides: L-Leu-L-Leu.2-methyl-2-propanol solvate (Görbitz, 1999b), L-Ala-L-Phe.2(2-propanol) (Görbitz, 1999a), L-Leu-L-Val.methanol (Görbitz & Torgersen, 1999), L-Val-L-Glu (Eggleston, 1984) and L-Leu-L-Tyr (Krause et al., 1993). The essential third amino H atom is accepted by a solvent molecule in the first three of these structure, and a normal functional group in a side chain in the last two. For L-Phe-Val, in contrast, the edge of the side chain phenyl group is the acceptor, Fig. 2. There are two H···C distances of 2.59 Å (Table 2), with an H···centroid distance of 2.93 Å. This is consistent with the fact that the title compound is only the second hydrophobic dipeptide that grows layered crystals devoid of solvent molecules.

Lately, much interest has been focused on the role of aromatic rings as hydrogen-bond acceptors (Desiraju & Steiner, 1999). A range of different donors can participate in X—H···Ph interactions, among them the positively charged amino group. It is, however, used very infrequently, as only eleven —NH3+··· Ph H-bonds were found in the 866 structures in the Cambridge Structural Database (Allen & Kennard, 1993) that contain both groups. Six of them (Bakshi et al., 1999; Bock et al., 1997; Steiner et al., 1997; Duatti et al., 1991), as well as one in a recently reported structure (Steiner & Mason, 2000), occur in special systems with tetraphenylborate anions as acceptors. The H atoms involved are often located more or less directly above the ring center with comparatively short H···centroid distances down to 2.13 Å. Weaker interactions in which the H atom is shifted closer to the ring edge (H···centroid distances in the range 2.39 to 2.96 Å) are found in the structures of L-Tyr-L-Val hydrate (Ramakrishnan et al., 1984), L-Tyr-L-Leu hydrate (Ramakrishnan & Viswamitra, 1988), pressinoic acid (a disulfide-linked hexapeptide constituting the cyclic moiety of Vasopressin; Langs et al., 1986), a peptide derivative containing phenylglycine (Coudert et al., 1996) and DL-o-tyrosine hydrochloride (Mostad et al., 1977). The —NH3+···Ph hydrogen bond found in the title structure is thus the sixth observed for a neutral acceptor. The rarity of this type of interaction can be explained by the fact that the amino group prefers to participate, whenever possible, in more traditional H bonds to strong acceptors, while the aromatic groups are more likely to be involved in interactions with weaker X—H donors.

When the peptide carbonyl group does not accept H atoms from N—H or O—H donors, as in the present structure, it is frequently observed to participate in weaker Cα—H···Oδb C interactions. Such a contact is also present here, but it is very long (Table 2), and the aromatic ring is donor in a shorter and more prominent hydrogen bond (Fig. 2).

In addition to their participation in hydrogen bonds as donors and acceptors, the phenyl rings are also engaged in aromatic stacking. A typical `herring-bone' pattern is generated by rings related by a twofold screw axis parallel to the 5.1 Å a axis. The centroid separation and interplanar angle are 5.68 Å and 67.3°, respectively. The shortest H···C distances for C(ar)—H···C(ar) contacts are 3.0 Å both for molecules related by the twofold screw and for molecules related by translation along the a axis. In conclusion, the phenyl group of L-Phe-L-Val is involved in intermolecular interactions to a much higher degree than usually observed in peptide structures.

Experimental top

L-Phe-L-Val was obtained from Sigma and used as received. Plate-shaped crystals were grown by slow evaporation of an aqueous solution of the peptide at 276 K.

Refinement top

Isotropic refinement of H atoms bonded to N, other H atoms were placed geometrically and refined with constraints to keep all C—H distances and C—C—H angles on one C atom the same. Free rotation of methyl groups was permitted. Uiso values were 1.2Ueq of the carrier atom, or 1.5Ueq for methyl groups. Intensities were measured for 1120 Friedel pairs. The absolute structure could not be established; the value for the Flack x parameter was 0.4 (8) (Flack, 1983). Friedel pairs were therefore merged in the final refinements.

NH3+···phenyl interactions in the Cambridge Structural Database (CSD version 5.19, April 2000, Allen & Kennard, 1993) were identified by searching for structures with at least one H···C distance < 2.8 Å. Additionally, the centroid—C···H angle was constrained to be in the range 60–120° to avoid hits for groups such as Ph—OH where the hydroxylic O atom is the true acceptor. Two structures with such interactions were still returned by the search and were subsequently rejected. A search for structures using an H···centroid distance < 3.1 Å as the only search criterion produced the same results.

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. The structure of L-Phe-L-Val with the atomic numbering indicated. Displacement ellipsoids are shown at the 50% probability level, and H atoms are shown as spheres of arbitrary size. The molecular conformation is semi-extended; all bond lengths and bond angles are normal.
[Figure 2] Fig. 2. The hydrogen bonding in a hydrophilic layer. The view direction is approximately parallel to the z axis (only one face of the unit cell is shown). Peptide main chains and the three classical hydrogen bonds between them are shown in black. The L-Phe side chain and the hydrogen bonds associated with it are shown in a grey halftone. The L-Leu side chain and all H atoms not directly involved in hydrogen bonding have been removed for clarity.
L-Phenylalanyl-L-valine top
Crystal data top
C14H20N2O3Dx = 1.293 Mg m3
Mr = 264.32Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 6612 reflections
a = 5.0955 (3) Åθ = 2.5–27.8°
b = 13.2155 (7) ŵ = 0.09 mm1
c = 20.1670 (11) ÅT = 150 K
V = 1358.04 (13) Å3Plate, colourless
Z = 40.60 × 0.60 × 0.05 mm
F(000) = 568
Data collection top
Siemens SMART CCD
diffractometer
1741 independent reflections
Radiation source: fine-focus sealed tube1655 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.014
Detector resolution: 8.3 pixels mm-1θmax = 27.8°, θmin = 2.5°
Sets of exposures each taken over 0.3° ω rotation scansh = 66
Absorption correction: empirical (using intensity measurements)
(SADABS; Sheldrick, 1996)
k = 1717
Tmin = 0.947, Tmax = 0.995l = 1926
8290 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.028H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.070 w = 1/[σ2(Fo2) + (0.0395P)2 + 0.2794P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.007
1741 reflectionsΔρmax = 0.19 e Å3
200 parametersΔρmin = 0.17 e Å3
0 restraintsAbsolute structure: see below
Primary atom site location: structure-invariant direct methods
Crystal data top
C14H20N2O3V = 1358.04 (13) Å3
Mr = 264.32Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.0955 (3) ŵ = 0.09 mm1
b = 13.2155 (7) ÅT = 150 K
c = 20.1670 (11) Å0.60 × 0.60 × 0.05 mm
Data collection top
Siemens SMART CCD
diffractometer
1741 independent reflections
Absorption correction: empirical (using intensity measurements)
(SADABS; Sheldrick, 1996)
1655 reflections with I > 2σ(I)
Tmin = 0.947, Tmax = 0.995Rint = 0.014
8290 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0280 restraints
wR(F2) = 0.070H atoms treated by a mixture of independent and constrained refinement
S = 1.06Δρmax = 0.19 e Å3
1741 reflectionsΔρmin = 0.17 e Å3
200 parametersAbsolute structure: see below
Special details top

Refinement. Refinement of F2 against ALL reflections. Three sets of exposures with the detector set at 2θ = 29°, crystal-to-detector distance 4.98 cm. Coverage of the unique set is over 99% complete to 50° in 2θ.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.5596 (2)1.07008 (8)0.21997 (5)0.0242 (2)
O20.5899 (2)0.72025 (8)0.15491 (5)0.0239 (2)
O30.2533 (2)0.80860 (8)0.19606 (6)0.0255 (3)
N11.0499 (3)1.14886 (9)0.25933 (7)0.0211 (3)
H11.101 (5)1.1594 (16)0.2148 (11)0.042 (3)*
H21.207 (5)1.1684 (17)0.2863 (10)0.042 (3)*
H30.900 (5)1.1920 (17)0.2705 (11)0.042 (3)*
N20.7887 (3)0.93278 (9)0.18387 (6)0.0176 (3)
H40.928 (4)0.8961 (13)0.1878 (8)0.021*
C10.9784 (3)1.04015 (10)0.26960 (7)0.0185 (3)
H111.127 (3)0.9977 (9)0.2607 (2)0.022*
C20.8939 (3)1.02917 (11)0.34262 (7)0.0224 (3)
H211.0308 (18)1.0583 (4)0.3711 (4)0.027*
H220.732 (2)1.0683 (5)0.34970 (12)0.027*
C30.8462 (3)0.92060 (12)0.36335 (7)0.0216 (3)
C41.0154 (3)0.87242 (13)0.40747 (8)0.0279 (4)
H411.166 (3)0.9089 (8)0.4251 (4)0.033*
C50.9716 (4)0.77240 (14)0.42664 (9)0.0338 (4)
H511.092 (3)0.7392 (8)0.4577 (7)0.041*
C60.7581 (4)0.72006 (13)0.40189 (8)0.0324 (4)
H610.7277 (8)0.6508 (15)0.4152 (3)0.039*
C70.5875 (4)0.76703 (13)0.35799 (8)0.0289 (4)
H710.434 (3)0.7291 (8)0.3399 (4)0.035*
C80.6308 (3)0.86708 (12)0.33918 (8)0.0240 (3)
H810.511 (3)0.8994 (7)0.3093 (6)0.029*
C90.7546 (3)1.01527 (10)0.22163 (7)0.0175 (3)
C100.5870 (3)0.89933 (10)0.13670 (7)0.0173 (3)
H1010.449 (3)0.9512 (9)0.13481 (8)0.021*
C110.7038 (3)0.88703 (11)0.06712 (7)0.0215 (3)
H1110.847 (3)0.8358 (10)0.06924 (8)0.026*
C120.8199 (4)0.98715 (14)0.04261 (9)0.0321 (4)
H1210.891 (3)0.9780 (3)0.0041 (6)0.046 (4)*
H1220.968 (2)1.0087 (6)0.0732 (5)0.046 (4)*
H1230.6781 (18)1.0411 (7)0.0424 (6)0.046 (4)*
C130.4937 (4)0.84887 (14)0.01943 (8)0.0324 (4)
H1310.5701 (11)0.8418 (10)0.0257 (5)0.045 (4)*
H1320.346 (2)0.8980 (7)0.0181 (5)0.045 (4)*
H1330.428 (2)0.7820 (9)0.0348 (4)0.045 (4)*
C140.4661 (3)0.80059 (10)0.16447 (7)0.0184 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0178 (5)0.0220 (5)0.0327 (6)0.0042 (5)0.0023 (5)0.0064 (4)
O20.0234 (5)0.0163 (5)0.0321 (6)0.0032 (4)0.0010 (5)0.0023 (4)
O30.0187 (5)0.0230 (5)0.0349 (6)0.0003 (5)0.0043 (5)0.0041 (5)
N10.0195 (7)0.0167 (5)0.0271 (7)0.0023 (5)0.0015 (6)0.0030 (5)
N20.0139 (6)0.0159 (5)0.0231 (6)0.0010 (5)0.0020 (5)0.0021 (5)
C10.0160 (7)0.0152 (6)0.0245 (7)0.0002 (6)0.0006 (6)0.0020 (5)
C20.0225 (7)0.0222 (7)0.0225 (7)0.0007 (6)0.0004 (6)0.0040 (6)
C30.0205 (7)0.0238 (7)0.0206 (6)0.0023 (6)0.0045 (6)0.0028 (6)
C40.0244 (8)0.0357 (9)0.0235 (7)0.0033 (8)0.0006 (7)0.0003 (7)
C50.0341 (9)0.0369 (9)0.0305 (8)0.0095 (9)0.0027 (8)0.0080 (7)
C60.0373 (9)0.0249 (8)0.0351 (8)0.0035 (8)0.0127 (8)0.0043 (7)
C70.0276 (8)0.0267 (8)0.0324 (8)0.0029 (7)0.0077 (7)0.0033 (7)
C80.0212 (7)0.0261 (8)0.0247 (7)0.0011 (6)0.0016 (6)0.0003 (6)
C90.0163 (7)0.0157 (6)0.0205 (6)0.0012 (6)0.0007 (6)0.0005 (5)
C100.0153 (7)0.0153 (6)0.0213 (6)0.0008 (6)0.0023 (6)0.0002 (5)
C110.0206 (7)0.0209 (6)0.0231 (7)0.0007 (6)0.0000 (6)0.0004 (6)
C120.0350 (10)0.0302 (8)0.0312 (8)0.0039 (8)0.0042 (8)0.0066 (7)
C130.0338 (10)0.0386 (9)0.0249 (7)0.0014 (9)0.0052 (7)0.0040 (7)
C140.0165 (6)0.0177 (6)0.0210 (6)0.0011 (6)0.0048 (6)0.0000 (5)
Geometric parameters (Å, º) top
O1—C91.2298 (19)C5—C61.383 (3)
O2—C141.2500 (17)C5—H510.9805
O3—C141.2623 (19)C6—C71.387 (2)
N1—C11.4964 (18)C6—H610.9661
N1—H10.95 (2)C7—C81.393 (2)
N1—H21.00 (2)C7—H710.9987
N1—H30.98 (2)C8—H810.9567
N2—C91.3411 (18)C10—C111.5329 (19)
N2—C101.4686 (18)C10—C141.5479 (19)
N2—H40.86 (2)C10—H1010.9837
C1—C91.531 (2)C11—C131.525 (2)
C1—C21.541 (2)C11—C121.531 (2)
C1—H110.9580C11—H1110.9974
C2—C31.514 (2)C12—H1211.0150
C2—H210.9823C12—H1221.0150
C2—H220.9823C12—H1231.0150
C3—C41.393 (2)C13—H1310.9945
C3—C81.394 (2)C13—H1320.9945
C4—C51.395 (2)C13—H1330.9945
C4—H410.9715
C1—N1—H1109.9 (13)C8—C7—H71120.0
C1—N1—H2111.5 (12)C7—C8—C3120.73 (16)
H1—N1—H2105 (2)C7—C8—H81119.6
C1—N1—H3109.8 (13)C3—C8—H81119.6
H1—N1—H3110.4 (19)O1—C9—N2124.61 (14)
H2—N1—H3110.3 (16)O1—C9—C1119.49 (12)
C9—N2—C10121.45 (13)N2—C9—C1115.89 (13)
C9—N2—H4120.8 (12)N2—C10—C11110.68 (12)
C10—N2—H4117.7 (12)N2—C10—C14107.34 (11)
N1—C1—C9107.46 (12)C11—C10—C14113.35 (12)
N1—C1—C2106.90 (11)N2—C10—H101108.5
C9—C1—C2112.05 (12)C11—C10—H101108.5
N1—C1—H11110.1C14—C10—H101108.5
C9—C1—H11110.1C13—C11—C12110.69 (14)
C2—C1—H11110.1C13—C11—C10109.85 (13)
C3—C2—C1113.45 (12)C12—C11—C10110.72 (13)
C3—C2—H21108.9C13—C11—H111108.5
C1—C2—H21108.9C12—C11—H111108.5
C3—C2—H22108.9C10—C11—H111108.5
C1—C2—H22108.9C11—C12—H121109.5
H21—C2—H22107.7C11—C12—H122109.5
C4—C3—C8118.61 (15)H121—C12—H122109.5
C4—C3—C2120.66 (15)C11—C12—H123109.5
C8—C3—C2120.72 (14)H121—C12—H123109.5
C3—C4—C5120.73 (17)H122—C12—H123109.5
C3—C4—H41119.6C11—C13—H131109.5
C5—C4—H41119.6C11—C13—H132109.5
C6—C5—C4119.99 (17)H131—C13—H132109.5
C6—C5—H51120.0C11—C13—H133109.5
C4—C5—H51120.0H131—C13—H133109.5
C5—C6—C7119.97 (16)H132—C13—H133109.5
C5—C6—H61120.0O2—C14—O3125.64 (13)
C7—C6—H61120.0O2—C14—C10117.34 (13)
C6—C7—C8119.97 (17)O3—C14—C10117.00 (12)
C6—C7—H71120.0
N1—C1—C9—N2128.94 (13)C4—C5—C6—C70.0 (3)
C1—C9—N2—C10178.82 (12)C5—C6—C7—C80.4 (2)
C9—N2—C10—C14109.57 (14)C6—C7—C8—C30.8 (2)
N2—C10—C14—O280.87 (15)C4—C3—C8—C70.9 (2)
N2—C10—C14—O397.69 (15)C2—C3—C8—C7179.68 (14)
N1—C1—C2—C3173.05 (13)C10—N2—C9—O11.0 (2)
C1—C2—C3—C4110.58 (16)N1—C1—C9—O151.21 (17)
N2—C10—C11—C1259.34 (16)C2—C1—C9—O165.93 (17)
N2—C10—C11—C13178.09 (13)C2—C1—C9—N2113.93 (14)
C9—C1—C2—C369.48 (17)C9—N2—C10—C11126.25 (14)
C1—C2—C3—C870.01 (19)C14—C10—C11—C1357.44 (17)
C8—C3—C4—C50.6 (2)C14—C10—C11—C12179.99 (14)
C2—C3—C4—C5179.97 (15)C11—C10—C14—O241.65 (18)
C3—C4—C5—C60.1 (2)C11—C10—C14—O3139.78 (13)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···C6i0.95 (2)2.59 (2)3.523 (2)170.4 (17)
N1—H1···C7i0.95 (2)2.59 (2)3.384 (2)142.2 (18)
N1—H2···O2i1.00 (2)1.72 (2)2.6926 (18)164 (2)
N1—H3···O3ii0.98 (2)1.85 (2)2.7662 (17)154 (2)
N2—H4···O3iii0.86 (2)2.03 (2)2.8907 (17)179.2 (18)
C1—H11···O1iii0.962.543.151 (2)122
C7—H71···O1iv1.002.423.132 (2)127
Symmetry codes: (i) x+2, y+1/2, z+1/2; (ii) x+1, y+1/2, z+1/2; (iii) x+1, y, z; (iv) x+1, y1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC14H20N2O3
Mr264.32
Crystal system, space groupOrthorhombic, P212121
Temperature (K)150
a, b, c (Å)5.0955 (3), 13.2155 (7), 20.1670 (11)
V3)1358.04 (13)
Z4
Radiation typeMo Kα
µ (mm1)0.09
Crystal size (mm)0.60 × 0.60 × 0.05
Data collection
DiffractometerSiemens SMART CCD
diffractometer
Absorption correctionEmpirical (using intensity measurements)
(SADABS; Sheldrick, 1996)
Tmin, Tmax0.947, 0.995
No. of measured, independent and
observed [I > 2σ(I)] reflections
8290, 1741, 1655
Rint0.014
(sin θ/λ)max1)0.657
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.028, 0.070, 1.06
No. of reflections1741
No. of parameters200
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.19, 0.17
Absolute structureSee below

Computer programs: SMART (Bruker, 1998), SAINT (Bruker, 1998), SAINT, SHELXTL (Sheldrick, 1997), SHELXTL.

Selected geometric parameters (Å, º) top
O1—C91.2298 (19)N1—C11.4964 (18)
O2—C141.2500 (17)N2—C91.3411 (18)
O3—C141.2623 (19)
N1—C1—C9—N2128.94 (13)N1—C1—C2—C3173.05 (13)
C1—C9—N2—C10178.82 (12)C1—C2—C3—C4110.58 (16)
C9—N2—C10—C14109.57 (14)N2—C10—C11—C1259.34 (16)
N2—C10—C14—O280.87 (15)N2—C10—C11—C13178.09 (13)
N2—C10—C14—O397.69 (15)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···C6i0.95 (2)2.59 (2)3.523 (2)170.4 (17)
N1—H1···C7i0.95 (2)2.59 (2)3.384 (2)142.2 (18)
N1—H2···O2i1.00 (2)1.72 (2)2.6926 (18)164 (2)
N1—H3···O3ii0.98 (2)1.85 (2)2.7662 (17)154 (2)
N2—H4···O3iii0.86 (2)2.03 (2)2.8907 (17)179.2 (18)
C1—H11···O1iii0.962.543.151 (2)122
C7—H71···O1iv1.002.423.132 (2)127
Symmetry codes: (i) x+2, y+1/2, z+1/2; (ii) x+1, y+1/2, z+1/2; (iii) x+1, y, z; (iv) x+1, y1/2, z+1/2.
 

Follow Acta Cryst. C
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds