J Chem Crystallogr (2011) 41:1328–1334

DOI 10.1007/s10870-011-0098-3

ORIGINAL PAPER

X-Ray Crystallographic Structure and Absolute

Configuration of the Cyclic Di-amino Acid Peptide:
Cyclo(L-HomoCySH-L-HomoCySH)
Andrew P. Mendham • John Spencer • Babur Z. Chowdhry •

Trevor J. Dines • Muhammad Mujahid • Rex A. Palmer •

Graham J. Tizzard • Simon J. Coles

Received: 22 December 2010 / Accepted: 15 April 2011 / Published online: 30 April 2011
Ó Springer Science+Business Media, LLC 2011

Abstract The cyclic di-amino acid peptide cyclo atoms are co-planar with the ring in each case. Ring atom
(L-homoCySH-L-homoCySH) [(3S, 6S)-3, 6-bis(2-sulfa- rms deviations, including the =O groups, are 0.0668,
nylethyl) piperazine-2,5-dione, C8H14N2O2S2, crystallizes 0.0658 and 0.0656 Å in molecules A, B and C, respec-
in the orthorhombic space group P212121 with unit cell tively. Details of the molecular geometry are compared
parameters a = 6.1509(2) Å, b = 18.0217(9) Å, c = with the compound cyclo(Gly-Gly) (Degeilh R, Marsh RE
29.6166(14) Å, V = 3283.0(2) Å3, Z = 12 (3 molecules, Acta Cryst 12:1007, 1959) and in addition some cyclic
A, B and C, per asymmetric unit), Dc = 1.422 g cm-3 and di-amino acid peptides in which the DKP rings have more
a linear absorption coefficient of 0.464 mm-1. The crystal puckered boat conformations.
structure determination was carried out with MoKa X-ray
data measured at 120(2) K. In the final refinement cycle Keywords Cyclic di-amino acid peptide

the data/restraints/parameter ratios were 5595/0/385 and Cyclic dipeptides
X-ray crystal structure

goodness-of-fit on F2 = 1.084. Final R indices for [I [ Absolute configuration
DKP ring conformations
2sigma(I)] were R1 = 0.0746, wR2 = 0.1356 and R indi-
ces (all data) R1 = 0.1092, wR2 = 0.1529. The largest
electron density difference peak and hole were 0.526 and Introduction
-0.445e Å-3. The DKP rings in all three molecules are
essentially, and unusually, planar and the C=O oxygen Cyclo(L-homoCySH-L-homoCySH) [(3S, 6S)-3, 6-bis
(2-sulfanylethyl)piperazine-2,5-dione], Fig. 1 (I), is an
example of a cyclic di-amino acid peptide (CDAP) in
which the amide groups adopt the cis conformation [1];
this is in contrast to linear peptides, the vast majority of
A. P. Mendham (&)
J. Spencer
B. Z. Chowdhry

M. Mujahid which possess amide bonds in the trans conformation.
School of Science, University of Greenwich, Medway Campus, CDAP’s are, structurally, fairly simple molecules and a
Central Avenue, Chatham Maritime, Kent ME4 4TB, UK number of X-ray structures have already been reported for
e-mail: [email protected]
this group of compounds [2]. Structural analyses have
T. J. Dines indicated that the diketopiperazine (DKP) ring adopts
Division of Electronic Engineering and Physics, either a planar (e.g. cyclo(Gly-Gly); [3]) or boat confor-
University of Dundee, Dundee DD1 4HN, UK mation (e.g. cyclo (L-Ala-L-Ala); [4]), in the solid state.
CDAP’s are commonly found in nature [5, 6] and inves-
G. J. Tizzard
S. J. Coles
UK National Crystallographic Service, School of Chemistry, tigations have been conducted on a number of CDAP
University of Southampton, Southampton SO17 1BJ, UK derivatives in relation to pharmacological applications
[7, 8]. Potentially, this group of compounds show promise
R. A. Palmer (&)
for use in diverse areas of chemistry and biology, including
School of Crystallography, Birkbeck College, University
of London, Malet Street, London WC1E 7HX, UK medicinal chemistry [9]. Herein we report the structure of
e-mail: [email protected] compound (I), Fig. 1.

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were refined anisotropically by full-matrix least squares

methods. CH3 and CH2 protons were set geometrically and
refined in riding mode. The two sulfur hydrogens for one of
the three molecules in the asymmetric unit (molecule A)
were located from a difference electron density map and
were found to refine isotropically with Uiso values of
0.04(2) for H1SA and 0.05(2) for H4SA. No suitable peaks
were found for the sulfur hydrogens on molecules B and C.
The sulfur hydrogens for molecule A were then removed
and 20 cycles of full matrix least squares were performed
Fig. 1 Ring numbering used for DKP survey (see also Table 3).
Codes for compounds used in survey are:(I) cyclo(L-homoCySH-L- on the structure without them. Using AFIX 147 in
homoCySH), R1 = 2-sulfanylethyl, R2 = H; (II) [3] cyclo(Gly-Gly), SHELXL-97 [17, 18] the hydrogen positions were now
R1 = R2 = H; (III) [27] cyclo(L-Met-L-Met), R1 = methionyl, CH2CH2 generated on S1A and S4A on molecule A and refined in
SCH3, R2 = H; (IV) [28] cyclo(L-Glu-L-Glu) R1 = CH2CH2OOH, riding mode. The positions for H1SA and H4SA generated
glutamyl, R2 = H; (V) [29] cyclo(L-Asp-L-Asp) R1 = aspartyl, CH2
COOH, R2 = H; (VI) [30] N,N0 -diacetyl-cyclo(Gly-Gly), R1 = H, in this way were very close to those determined from the
R2 = acetyl difference electron density and refined previously. Conse-
quently the hydrogen positions were generated using the
Experimental same AFIX 147 protocol for H1SB and H2SB in molecule
B, and for H1SC and H2SC in molecule C. As far as could
(I) was synthesized using the method reported by duVig- be judged the six sulfur hydrogen positions generated in
neaud et al [10]. Crystals for X-ray analysis were prepared this way appeared to be in acceptable locations and were
by slow evaporation of a solution of (I) in absolute ethanol. retained as part of the final structure. An extinction
parameter which had been included in the refinement to
Data Collection this point was found to have a value of 0.0(3). The least
squares refinement was therefore repeated excluding the
A colourless crystal fragment of size 0.12 9 0.03 9 extinction parameter. All tables, diagrams and discussions
0.02 mm3 was mounted on a glass fibre and flash frozen to are based on this final refinement protocol. Geometrical
120 K. Intensities were collected, using monochromated calculations were made using the programs PARST and
MoKa radiation, k = 0.71073 Å, on a Nonius Kappa CCD PLATON [20] as implemented in WinGX. In the final
diffractometer, employing / and x scans. Programs used refinement cycles there were 5595 data to 385 parameters,
were: unit cell determination with the program DirAx [11]; resulting in a final Goodness-of-fit on F2 of 1.084 and final
data collection controlled by Collect [12]; data reduction R indices [I [ 2sigma(I)] of R1 = 0.0746, wR2 = 0.1356.
and cell refinement using the program Denzo [13]; an The largest and smallest difference electron density regions
absorption correction was made with SORTAV [14, 15]. were ?0.526e Å-3 and -0.445e Å-3. The Flack [21]
The diffractometer was equipped with an Oxford Cryo- absolute structure parameter = 0.2(1). The crystal struc-
systems ‘‘Cryostreams’’ 700 [16], enabling the data to be ture is therefore determined with the correct absolute
collected at 120 K. The crystals are orthorhombic space configuration and all relevant tables and figures are based
group P212121 with unit cell parameters a = 6.1509(2) Å, on this configuration. Crystal data are summarized in
b = 18.0217(9) Å, c = 29.6166(14) Å, V = 3283.0(2) Å3, Table 1.
Z = 12 (3 molecules, A, B and C, per asymmetric unit),
density (calculated) = 1.422 g cm-3 and a linear absorp-
tion coefficient of 0.464 mm-1. In total 14694 integrated Results and Discussion
reflections were collected, reducing to a data set of 5595
unique with R(int) = 0.0638, and completeness of data (to Figure 1 (I) shows the chemical scheme and Fig. 2 (I) the
theta = 24.99°) of 98.4%. The resolution range was atom numbering for cyclo(L-HomoCySH-L-HomoCySH).
6.020–0.841 Å. There was no significant variation in ORTEP [22] and RASTER3D [23], as implemented in
intensity during the course of data collection. WinGX, were used to prepare Fig. 3a–c for molecule A, B
and C, respectively showing the thermal ellipsoids.
X-ray Structure Analysis
Molecular Geometry
The crystal structure was solved by Direct Methods and
refined using SHELXL-97 [17, 18] implemented in the Bond lengths are determined approximately to ±0.009 Å
WinGX system of programs [19]. Non-hydrogen atoms and bond angles to ±(0.5–0.6°). Corresponding bond

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Table 1 Crystal data and

Identification code 2008src1129 CCDC799784
structure refinement for cyclo(L-
homoCySH-L-homoCySH) Empirical formula C8H14N2O2S2
[2008src1129] Formula weight 234.33
Temperature 120(2) K
Wavelength 0.71073 Å
Crystal system Orthorhombic
Space group P212121
Unit cell dimensions a = 6.1509(2) Å a = 90°
b = 18.0217(9) Å b = 90°
c = 29.6166(14) Å c = 90°
Volume 3283.0(2) Å3
Z 12 (3 independent molecules/asymmetric unit)
Dc 1.422 g cm-3
Absorption coefficient 0.464 mm-1
F(000) 1488
Crystal Needle; colourless
Crystal size 0.12 9 0.03 9 0.02 mm3
h range for data collection 3.38–24.99°
F(000) 1488
Crystal size 0.12 9 0.03 9 0.02 mm3
Theta range for data collection 3.38–24.99°.
Index ranges -7 B h B 7, -21 B k B 21, -35 B l B 33
Reflections collected 14694
Independent reflections 5595 [R (int) = 0.0638]
Completeness to theta = 24.99° 98.4%
Max. and min. transmission 0.9908 and 0.9464
Refinement method Full-matrix least-squares on F2
Data/restraints/parameters 5595/0/385
Goodness-of-fit on F2 1.084
Final R indices [I [ 2sigma (I)] R1 = 0.0746, wR2 = 0.1356
R indices (all data) R1 = 0.1092, wR2 = 0.1529
Absolute structure parameter 0.2(1)
Largest diff. peak and hole 0.526 and -0.445e Å-3

lengths across the three molecules are in good agreement angle: N–C–Ca & 119.4°, N–Ca–C 112.5°, and Ca–N–
with the expected C2 symmetry. There is a slightly wider C & 127.2°. In the two sulfanylethyl side chains there is a
variation in the corresponding bond angles. slightly wider variation of values e.g., C(1A)–C(11A)–
C(12A) = 114.2(5)°, C(4A)–C(41A)–C(42A) = 111.5(5)°.
Bond Lengths
DKP Ring Conformations and Planarity
All bonds lengths in the DKP rings are consistent with
The absolute ring torsion angles are all small, with a
accepted values in peptides [24] and, C–C and C–S bonds
maximum of 18.0°, and average values of 6.2°, 10.2° and
in the sulfanylethyl side chains are also normal [25].
5.1° in molecules A, B and C, respectively (see Table 3
(IA, B, C)). The DKP rings A, B and C, including the =O
Bond Angles atoms are essentially planar with rms deviations of 0.0668,
0.0658 and 0.0656 Å, respectively. In all cases the two
Except for those indicated by an asterisk in Table 2, bond opposite side chains are on the same side of the ring plane,
angles in the DKP rings are consistent with accepted values thus maintaining the pseudo C2 (2) symmetry associated
in peptides [24]. There are three distinct types of ring bond with other features of the molecular geometry.

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presumably because they are too long. This simplification

leaves three almost identical H-bonded ribbons, of which
the one for molecule A is shown in Fig. 4, the other two in
molecules B and C being remarkably similar .

Fig. 2 Schematic chemical structure and atom numbering for

cyclo(L-homoCySH-L-homoCySH)
Comparison With Cyclo(Gly-Gly) and Other DKP’s

Comparison With Cyclo(Gly-Gly)

The crystal structure of the compound cyclo(Gly-Gly)

Fig. 1 (II), was published in 1959 by Degeilh and Marsh
[3]. It is of interest to compare the molecular structure of
(I), presented here, where the R groups on the Ca‘s are
sulfanylethyls, with that of (II) where both R groups are
–H. Table 2 compares the corresponding ring bond lengths,
bond angles and peptide x angles for the two structures.
Standard peptide values are also included [24]. Ring tor-
sion angles can be found in Table 3. Note: (1) molecule
(II) as determined by Degeilh and Marsh [3] is required by
the space group to be located on a crystallographic center
of symmetry, which means, as can be seen in Tables 2 and
4 (see next section), that the geometrical parameters across
the molecule are exactly equal; (2) the esd’s given in [3]
are unrealistically small and have been omitted. In general
the corresponding bond lengths round the rings follow the
same trends in (IA, B, C)) and (II), Fig. 1, the actual values
generally match very well and with standard values [24].
The external ring bond angles involving the O= group also
agree well. The ring bond angle values between (I) and (II)
follow similar trends but differ noticeably in some instan-
ces either from each other or from standard values. These
Fig. 3 a Cyclo(L-homoCySH-L-homoCySH), molecule A. Drawn are indicated by an asterisk in Table 2 and occur when the
with Ortep/Raster [22, 23]. Thermal ellipsoids are shown at 50% central atom is either N or C(O). Bond angles where Ca is
probability. b Cyclo(L-homoCySH-L-homoCySH), molecule B. the central atom generally agree much better. The planarity
Drawn with Ortep/Raster [22, 23]. Thermal ellipsoids are shown at
of the DKP ring in (II) [3] is explained by Degeilh and
50% probability. c Cyclo(L-homoCySH-L-homoCySH), molecule C.
Drawn with Ortep/Raster [22, 23]. Thermal ellipsoids are shown at Marsh as a conjugative effect throughout the ring. The
50% probability planarity of the DKP ring in (II) is unexpected and is quite
unusual in this type of compound and is discussed in the
Side Chain Conformations next section.

The sulfanylethyl side chains on each side of the molecule Comparison With Other DKP’s
have the following conformations: coiled/extended;
extended/extended; extended/coiled, in molecules A, B and It is of interest to investigate factors which may determine
C, respectively. whether the DKP ring is planar, as in structures (I) reported
here, and (II) [3], or puckered as in other cyclic di-amino
Crystal Packing acid peptides structures as for example in the selected
references [27–30], discussed below. We discuss here the
The crystal packing is governed by S–H–O and N–H–O following structures as shown in Fig. 1: (I) cyclo(L-homo-
hydrogen bonds (Table 4 and Fig. 3a–c drawn with CySH-L-homoCySH) (this report) with three molecules
MERCURY [26]). Unusually, not all potential H bonds are A, B and C per asymmetric unit; (II) cyclo(Gly-Gly) [3];
formed. MERCURY does not include S(4A)–H(4SA)


(III) [27] cyclo(L-methionyl-L-methionyl); (IV) [28]
O(3C) and S(4C)–H(4SC)


O(3A) interactions (Table 4), cyclo(L-Glu-L-Glu) with 2 polymorphs A and B; (V) [29]

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Table 2 Ring bond lengths [Å] and angles [°] and x [°] for (IA), (IB), (IC) and (II) [9]
(IA) (IB) (IC) (II) Standard value [24] Peptide notation

Bond lengths [Å]

C(1)–N(2) 1.475(8) 1.456(8) 1.450(7) 1.449 1.458 Ca–N
N(2)–C(3) 1.314(8) 1.312(8) 1.328(7) 1.326 1.329 N–C(O)
C(3)–C(4) 1.524(9) 1.512(8) 1.529(8) 1.499 1.525# C(O)–Ca
C(4)–N(5) 1.468(8) 1.461(7) 1.453(7) 1.449 1.458 Ca–N
N(5)–C(6) 1.318(7) 1.340(8) 1.338(8) 1.326 1.329 N–C(O)
C(1)–C(6) 1.508(8) 1.513(8) 1.508(8) 1.499 1.525# Ca–C(O)
C(6)–O(6) 1.246(7) 1.242(8) 1.240(7) 1.239 1.231 C(O)=O
C(3)–O(3) 1.244(7) 1.249(7) 1.236(7) 1.239 1.231 C(O)=O
# 1.516 for Gly
Bond angles [°]
N(2)–C(1)–C(6) 112.5(5) 112.2(5) 113.2(5) 115.1* 111.2 N–Ca–C(O)
C(3)–N(2)–C(1) 127.0(5)* 127.7(5)* 128.1(5)* 126.0* 121.7 C(O)–N–Ca
N(2)–C(3)–C(4) 120.1(6)* 119.1(6)* 118.4(5)* 118.9* 116.2 N–C(O)–Ca
N(5)–C(4)–C(3)* 111.7(5) 112.8(5) 113.1(5) 115.1* 111.2 N–Ca–C(O)
C(6)–N(5)–C(4)* 127.9(5)* 125.5(5)* 127.3(5)* 126.0* 121.7 C(O)–N–Ca
N(5)–C(6)–C(1) 119.6(5)* 119.6(6)* 119.1(5)* 118.9 116.2 N–C(O)–Ca
N(2)–C(3)–O(3) 122.5(6) 122.5(6) 123.5(6) 122.6 123.0 N–C(O)=O
C(4)–C(3)–O(3) 117.4(6) 118.1(5) 118.1(5) 118.5 120.8 Ca–C(O)=O
C(1)–C(6)–O(6) 117.8(5) 119.2(6) 118.3(6) 118.5 120.8 Ca–C(O)=O
N(5)–C(6)–O(6) 122.6(6) 121.2(6) 122.4(5) 122.6 123.0 N–C(O)=O
x torsion angles [°]
H(2)–N(2)–C(3)–O(3) 0.6 7.2 1.6 2.0 0.0
H(5)–N(5)–C(6)–O(6) -1.7 9.4 0.9 1.6 0.0
Except for those indicated by an asterisk (*) bond angles in the DKP rings are consistent with accepted values in peptides [24]

Table 3 DKP ring torsion angles for eleven cyclic di-peptide molecules
DKP Ring s (8) (IA) (IB) (IC) (II) (III) (IVP1) (IVP2) (VA) (VB) (VIA) (VIB)

s1 -1.8(9) 2.2(9) 2.1(9) 1.33 9.6(2) 4.2(3) 4.3(2) 1.3(6) 3.6(6) 3.3(2) 5.4(2)
s2 -0.7(9) 7.4(10) 1.0(9) -1.33 1.8(3) 11.2(3) 4.3(2) 5.5(6) 4.1(6) 4.8(2) 8.1(2)
s3 10.0(8) -13.1(9) 5.7(9) 1.29 -32.9(2) -30.6(3) -34.9(2) -34.1(5) -36.9(6) -46.4(2) -49.1(2)
s4 9.1(8) -18.0(8) 6.8((9) -1.29 -25.5(2) -37.6(3) -34.9(2) -37.9(6) -37.4(6) -47.7(2) -51.8(2)
s5 -8.6(8) 8.1(9) -7.2(8) -1.19 26.1(2) 22.1(3) 29.7(2) 30.3(5) 32.3(5) 41.8(2) 41.2(2)
s6 -7.5(8) 13.0(8) -8.1(8) 1.19 19.1(2) 28.8(3) 29.7(2) 33.8(5) 32.8(6) 43.1(2) 43.9(2)
See Fig. 1 for ring atom numbering scheme
[Codes for torsion angles: s1 = C4–C3–N2–C1; s2 = C1–C6–N5–C4
s3 = C3–N2–C1–C6; s4 = C6–N5–C4–C3; s5 = N2–C1–C6–N5; s6 = N5–C4–C3–N2]
Notes: In (I) there are three independent molecules A, B and C. In (IV) there are two different polymorphic crystal forms P1 and P2. In (V) in the
two crystallographically independent molecules A and B the diketopiperazine ring takes on the same boat conformation with corresponding
atoms forming the boat and pseudo symmetry C2v (mm2). Molecule (I) A and B is cyclo(L-homoCySH-L-homoCySH), this report; molecule (II)
is cyclo(Gly-Gly) [9]; molecule (III) is cyclo(L-Met-L-Met) [27]; molecule (IV) is cyclo(L-Glu-L-Glu) with 2 polymorphs A and B [28]; molecule
(V) is cyclo(L-Asp-L-Asp) with 2 molecules A and B per asymmetric unit [29]; molecule (VI) is N,N0 -diacetyl-cyclo(Gly-Gly) with two
molecules A and B per asymmetric unit [30]. In structures (I)–(VI) the peptide R1 groups are L-homoCySH, H, L-methionyl, L-glutamyl,
L-aspartyl, and H, respectively. In (VI) the amide N’s are modified by acetylation

cyclo(L-aspartyl-L-aspartyl) with 2 molecules A and B per H, L-methionyl, L-glutamyl, L-aspartyl, and CH3CO, respec-
asymmetric unit; (VI) [30] N,N0 -diacetyl-cyclo(Gly-Gly) tively. In (VI) the amide N’s are modified by acetyla-
with two molecules A and B per asymmetric unit. In tion. Structures (I) and (II) have planar DKP rings
structures (I)–(VI) the peptide R1 groups are L-homoCySH, whereas the DKP rings in (III), (IV), (V) and (VI) display

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Table 4 Hydrogen bonds for cyclo(L-homoCySH-L-homoCySH)

[2008src1129] [Å and °]
D–H


A d(D–H) d(H


A) d(D


A) \(DHA)

S(4A)–H(4SA)


O(3C)#1 1.17 2.50 3.647(5) 157.8

N(5A)–H(5A)


O(3A)#1 0.88 2.00 2.879(6) 173.7
N(2A)–H(2A)


O(6A)#2 0.88 1.99 2.871(7) 174.5
N(5B)–H(5B)


O(3B)#2 0.88 1.99 2.838(6) 161.1
N(2B)–H(22 N)


O(6B)#1 0.88 1.98 2.848(6) 167.7
N(5C)–H(5C)


O(3C)#1 0.88 1.97 2.851(6) 173.9
N(2C)–H(2C)


O(6C)#2 0.88 1.98 2.860(6) 173.5
Symmetry transformations used to generate equivalent atoms
#1 x ? 1, y, z; #2 x - 1, y, z

Fig. 5 Cyclo(Gly-Gly) [3] (drawn with Accelrys Visualizer [31]

showing the highly planar DKP ring

Supplementary Material

Crystallographic data (excluding structure factors) for the

structure reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supple-
mentary publication nos. CCDC 799784. Copies of avail-
able material can be obtained, free of charge via www.
Fig. 4 Cyclo(L-homoCySH-L-homoCySH), H-bond ribbon involving ccdc.cam.ac.uk/conts/retrieving.html or on application to
molecule A. Drawn with MERCURY [26]. Corresponding ribbons for the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ,
molecules B and C are very similar UK (fax: ?44-(0) 1223-336033 or e-mail: teched @
chemcrys.cam.ac.uk).

boat conformations. DKP ring torsion angles for these

eleven molecules are shown in Table 3. From the data in
Table 3 it can be seen that the values of both s1 = C4–C3– References
N2–C1 and s2 = C1–C6–N5–C4 are small in all 11 mol-
ecules listed here. 1. Bowman RL, Kellerman M, Johnson WC Jr (1983) Biopolymers
22:1045
These are the two peptide group torsion angles, x in
2. Ramnaryan K, Ramakrishnan C (1987) J Biosci 12(4):331
protein structure notation, and their values are consistent 3. Degeilh R, Marsh RE (1959) Acta Cryst 12:1007
with those of a typical cis peptide where the amide group is 4. Sletten E (1970) J Am Chem Soc 92:172
roughly flat. It is worth noting that x is consistent with this 5. Prasad C (1995) Peptides 16:151
6. Hernandez IJC, Macedo ML, Berlinck RGS, Ferreira AG, God-
pattern even in molecules V(A and B) where R2, normally
inho MJL (2004) J Braz Chem Soc 15:441
H, is modified by acetylation [30]. In molecules I(A, B and 7. Braun SC, Milne PJ, Naude R, Van de Venter M (2004) Anti-
C), reported here, where R1 = homoCySH, and molecule cancer Res 24:1713
(II) [9] where R1 = H, all six ring torsion angles are small, 8. Milne PJ, Hunt AL, Rostoll K, Van der Walt JJ, Graz CJM (1998)
J Pharm Pharmacol 50:1331
the overall DKP ring being roughly flat. This is more
9. Wang S, Golec J, Miller W, Milutinovic S, Folkes A, Williams S,
acceptable in (II), Fig. 5 [31], where the planarity of the Brooks T, Hardman K, Charlton P, Wren S, Spencer J (2002)
DKP ring was explained by Degeilh and Marsh [3] as Bioorg Med Chem Lett 12:2367; and references cited
extended conjugation, than in I which is chemically similar 10. duVigneaud V, Patterson WI, Hunt M (1938) J Biol Chem
126:217
to molecules (III), (IV, P1 and P2), and (V, A and B)
11. Duisenberg AJM (1992) J Appl Cryst 25:92
where R1, as in (I) itself, is in each case a typical protein 12. Hooft R (1998) Collect: data collection software. Nonius BV
side group and (VI, A and B) where the amide N’s are 13. Otwinowski Z, Minor W (1997) methods in enzymology. In:
modified by acetylation. It may therefore be of interest to Carter Jr CW, Sweet RM (eds) Macromolecular crystallography,
part A, vol 276. Academic Press, London, pp 307–326
further investigate reasons why the DKP ring in molecules
14. Blessing RH (1995) Acta Cryst A51:33
I (A, B and C) are unusually and, perhaps, unexpectedly 15. Blessing RH (1997) J Appl Cryst 30:421
planar. 16. Cosier J, Glazer MJ (1986) J Appl Cryst 19:105

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