Cyclo(l-tyrosyl-l-tryptophanyl) dimethylformamide solvate

Carl Henrik Görbitz; Lars Male Hartviksen

doi:10.1107/S1600536808000640

. 2008 Jan 11;64(Pt 2):o436. doi: 10.1107/S1600536808000640

Cyclo(l-tyrosyl-l-tryptophanyl) dimethylformamide solvate

Carl Henrik Görbitz ^a,^*, Lars Male Hartviksen ^a

PMCID: PMC2960427 PMID: 21201463

Abstract

The structure of the title compound [systematic name: (3S,6S)-3-(4-hydroxybenzyl)-6-(1H-indol-3-ylmethyl)piperazine-2,5-dione dimethylformamide solvate], C₂₀H₁₉N₃O₃·C₃H₇NO, contains hydrogen-bonded tapes typical for diketopiperazines. The structure is stabilized by strong intermolecular interactions of the types O—H⋯O and N—H⋯O involving the dipeptide and the solvent molecules. The absolute configuration was known from the starting materials.

Related literature

For related structures, see: Morris et al. (1974 ▶); Grant et al. (1999 ▶); Suguna et al. (1984 ▶); Lin & Webb (1973 ▶); Razak et al., (2000 ▶); Luo & Palmore (2002 ▶); Görbitz (1987 ▶); Görbitz & Hartviksen (2006 ▶). Solvent inclusion: Görbitz & Hersleth (2000 ▶). Cambridge Structural Database: Allen (2002 ▶).

Experimental

Crystal data

C₂₀H₁₉N₃O₃·C₃H₇NO
M _r = 422.48
Monoclinic,
a = 6.1923 (2) Å
b = 15.3873 (5) Å
c = 11.3780 (3) Å
β = 96.661 (1)°
V = 1076.81 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 105 (2) K
0.80 × 0.65 × 0.20 mm

Data collection

Siemens SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.800, T _max = 0.982
9514 measured reflections
2786 independent reflections
2454 reflections with I > 2σ(I)
R _int = 0.038

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.122
S = 1.15
2786 reflections
297 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT-Plus (Bruker, 2001 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL (Bruker, 2000 ▶); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808000640/pv2058sup1.cif

e-64-0o436-sup1.cif^{(21.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808000640/pv2058Isup2.hkl

e-64-0o436-Isup2.hkl^{(136.8KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1ⁱ	0.96 (3)	1.94 (3)	2.902 (3)	174 (3)
N2—H2⋯O3ⁱⁱ	0.87 (3)	2.01 (3)	2.884 (3)	178 (3)
N3—H3⋯O1ⁱⁱⁱ	0.81 (4)	2.16 (4)	2.851 (3)	144 (3)
O2—H4⋯O1D	1.04 (5)	1.59 (5)	2.606 (3)	163 (4)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

The purchase of the diffractometer was made possible through support from the Research Council of Norway (NFR).

supplementary crystallographic information

Comment

The title compound, (3S,6S)-3-(4-hydroxsybenzyl)-6 -(1H-indol-3-yl)methylpiperazine-2,5-dione dimethylformamide solvate, (I), was obtained as the result of an attempt to crystallize the corresponding linear dipeptide Tyr-Trp from a dimethylformamide solution. In our laboratory we have previously observed similar cyclization reactions taking place for several other dipeptides including Asp-Ala (Görbitz, 1987), Ile-Ile (Görbitz & Hartviksen, 2006) and Val-Leu (unpublished results).

The crystal structure of (I) contains straight hydrogen-bonded tapes as seen in Fig. 2. A search in the Cambridge Structural Database (CSD; Version 5.28 of November 2006; Allen 2002) revealed 59 examples of such tapes (unperturbed e.g. by additional cyclic connections between the two C^α-atoms). The periodicity of this pattern, usually corresponding to a unit-cell parameter, shows a quite narrow distribution with 54 out of 59 observations in the range 6.06 to 6.26 Å, with 6.19 Å observed for (I) being close to the 6.16 Å average value. The full range observed in the CSD is from 6.01 to 6.57 Å, with the upper limit being represented by a distinct outlier (piperazine-2,5-dione:2,5-dihydroxyterephatlic acid 1:1, Luo & Palmore, 2002).

The carbonyl O atom of the cocrystallized dimethylformamide (DMF) solvent molecule accepts a H atom from the Tyr hydroxyl group, but the DMF molecule is also involved in a number of weaker hydrogen bonds (Table 2 and Fig. 2). This is in line with previous findings that DMF molecules are often more heavily involved in intermolecular interactions than one traditionally would expect (Görbitz & Hersleth, 2000).

From the 20 naturally occurring amino acids one can construct 210 different cyclic dipeptides (as opposed to 400 linear dipeptides). Single crystal structural studies have been presented for 20 of them, including four structures with Tyr or Trp residues: cyclo(Gly-Trp) (Morris et al., 1974), cyclo(Trp-Trp) DMSO solvate (Grant et al., 1999), cyclo(Leu-Tyr) hydrate (Suguna et al., 1984), and cyclo(Ser-Tyr) hydrate (Lin & Webb, 1973). From a conformational point of view these four peptides resemble (I) as well as each other, and all except cyclo(Trp-Trp) crystallize in the P2₁ space group. Nevertheless, each cyclic dipeptide has its own unique packing arrangement, also when all other compounds with a diketopiperazine moiety are considered.

Experimental

The corresponding linear peptide Tyr-Trp was obtained from Bachem. Crystals of the cyclic analogue resulting from ring closure were obtained by slow evaporation of a solution of Tyr-Trp in dimethylformamide.