Crystal structure and packing energy calculations of (+)-6-amino­penicillanic acid

The X-ray single-crystal structure of (2S,5R,6R)-6-amino-3,3-dimethyl-7-oxo-4-thia-1-aza­bicyclo­[3.2.0]heptane-2-carb­oxy­lic acid, commonly known as (+)-6-amino­penicillanic acid (C₈H₁₂N₂O₃S) and a precursor of a variety of semi-synthetic penicillins, has been determined from synchrotron data at 150 K. The structure represents an ordered zwitterion and the crystals are nonmerohedrally twinned. The crystal structure is composed of a three-dimensional network built by three charge-assisted hydrogen bonds between the ammonium and carboxyl­ate groups. The complementary analysis of the crystal packing by the PIXEL method brings to light the nature and ranking of the energetically most stabilizing inter­molecular inter­action energies. In accordance with the zwitterionic nature of the structure, PIXEL lattice energy calculations confirm the predominance of the Coulombic term (-379.1 kJ mol^-1) ahead of the polarization (-141.4 kJ mol^-1), dispersion (-133.7 kJ mol^-1) and repulsion (266.3 kJ mol^-1) contributions.

Computing details

Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008a); program(s) used to refine structure: SHELXL2012 (Sheldrick, 2008a); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: publCIF (Westrip, 2010).

(2S,5R,6R)-6-Amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Crystal data

C8H12N2O3S	Dx = 1.502 Mg m^−3
Mr = 216.26	Synchrotron radiation, λ = 0.71075 Å
Orthorhombic, P212121	Cell parameters from 2730 reflections
a = 6.1954 (4) Å	θ = 2.4–25.6°
b = 10.4543 (7) Å	µ = 0.32 mm^−1
c = 14.7654 (9) Å	T = 150 K
V = 956.33 (11) Å^3	Block, colourless
Z = 4	0.08 × 0.06 × 0.04 mm
F(000) = 456

Data collection

Bruker SMART APEXII CCD area-detector diffractometer	2130 independent reflections
Radiation source: fine-focus sealed tube	1966 reflections with I > 2σ(I)
Silicon monochromator	Rint = 0.043
ω scans	θmax = 25.6°, θmin = 2.4°
Absorption correction: multi-scan (TWINABS; Sheldrick, 2008b)	h = −7→7
Tmin = 0.643, Tmax = 0.745	k = −12→12
2130 measured reflections	l = −17→17

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.029	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.073	w = 1/[σ^2(Fo^2) + (0.034P)^2 + 0.1358P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max < 0.001
2130 reflections	Δρmax = 0.21 e Å^−3
142 parameters	Δρmin = −0.20 e Å^−3
0 restraints	Absolute structure: Flack x parameter determined using 678 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons & Flack, 2004)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.06 (6)

Special details

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. From TWINABS: 6566 data (1807 unique) involve domain 1 only, mean I/σ 12.9; 6634 data (1806 unique) involve domain 2 only, mean I/σ 13.4; 590 data (349 unique) involve 2 domains, mean I/σ 21.2. The quoted R_int value (0.043) comes from scaling all single and composite reflections involving both domains. R_int = 0.039 from scaling all singles of domain 2. R_int = 0.0554 from scaling single and composite reflections of domain 1. For the generation of an HKLF5 file, all observations containing domain 2 were chosen. Data were merged in TWINABS according to point group 222; single reflections that also occur in composites were included for merging.

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

	x	y	z	Uiso*/Ueq
N1	0.7032 (4)	0.5375 (2)	0.71283 (16)	0.0181 (5)
C2	0.6065 (5)	0.5155 (2)	0.80083 (18)	0.0172 (6)
H2	0.4597	0.4774	0.7927	0.021*
C3	0.5848 (5)	0.6508 (3)	0.84665 (19)	0.0174 (6)
S4	0.79266 (11)	0.75459 (7)	0.79121 (5)	0.01909 (19)
C5	0.8738 (5)	0.6344 (2)	0.70872 (19)	0.0180 (6)
H5	1.0223	0.5997	0.7188	0.022*
C6	0.8143 (5)	0.6525 (3)	0.60750 (18)	0.0196 (6)
H6	0.9168	0.6046	0.5677	0.023*
C7	0.6148 (5)	0.5693 (3)	0.6307 (2)	0.0211 (6)
C8	0.7478 (5)	0.4232 (2)	0.85603 (18)	0.0170 (6)
O9	0.6525 (4)	0.34077 (19)	0.90362 (13)	0.0211 (5)
O10	0.9474 (3)	0.4377 (2)	0.84992 (15)	0.0249 (5)
C11	0.6248 (6)	0.6501 (3)	0.94842 (19)	0.0241 (7)
H11A	0.7699	0.6170	0.9607	0.036*
H11B	0.5175	0.5954	0.9781	0.036*
H11C	0.6126	0.7374	0.9720	0.036*
C12	0.3620 (5)	0.7053 (3)	0.8262 (2)	0.0237 (7)
H12A	0.3524	0.7927	0.8498	0.036*
H12B	0.2516	0.6520	0.8551	0.036*
H12C	0.3387	0.7063	0.7606	0.036*
N13	0.7738 (5)	0.7812 (2)	0.57153 (17)	0.0185 (5)
H13A	0.883 (7)	0.841 (4)	0.594 (3)	0.048 (12)*
H13B	0.630 (8)	0.810 (4)	0.586 (3)	0.044 (11)*
H13C	0.781 (7)	0.776 (4)	0.511 (3)	0.049 (12)*
O14	0.4475 (4)	0.5422 (2)	0.59357 (15)	0.0317 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0218 (12)	0.0164 (11)	0.0160 (11)	−0.0014 (9)	−0.0010 (10)	−0.0006 (10)
C2	0.0179 (15)	0.0160 (13)	0.0178 (15)	−0.0017 (11)	−0.0014 (12)	0.0026 (11)
C3	0.0174 (16)	0.0162 (13)	0.0186 (15)	−0.0009 (11)	−0.0004 (11)	0.0017 (12)
S4	0.0185 (3)	0.0183 (3)	0.0205 (3)	−0.0030 (3)	0.0005 (3)	−0.0029 (3)
C5	0.0182 (14)	0.0170 (13)	0.0188 (14)	−0.0004 (11)	−0.0003 (13)	0.0010 (12)
C6	0.0256 (17)	0.0181 (13)	0.0149 (14)	−0.0005 (13)	0.0020 (12)	−0.0028 (11)
C7	0.0278 (17)	0.0171 (14)	0.0185 (15)	−0.0027 (12)	−0.0014 (13)	−0.0027 (11)
C8	0.0204 (17)	0.0148 (12)	0.0158 (13)	0.0001 (11)	−0.0005 (11)	−0.0027 (11)
O9	0.0225 (12)	0.0224 (10)	0.0185 (10)	−0.0028 (8)	−0.0016 (9)	0.0067 (8)
O10	0.0175 (12)	0.0265 (11)	0.0308 (12)	0.0036 (8)	0.0013 (9)	0.0069 (10)
C11	0.0306 (18)	0.0232 (14)	0.0186 (15)	0.0056 (14)	−0.0005 (13)	−0.0012 (12)
C12	0.0193 (16)	0.0222 (14)	0.0295 (16)	0.0023 (11)	0.0012 (14)	0.0049 (13)
N13	0.0201 (14)	0.0200 (12)	0.0153 (12)	−0.0017 (10)	0.0002 (11)	0.0002 (9)
O14	0.0369 (14)	0.0318 (12)	0.0265 (12)	−0.0142 (11)	−0.0123 (10)	0.0039 (10)

Geometric parameters (Å, º)

N1—C7	1.372 (4)	C6—H6	1.0000
N1—C2	1.449 (4)	C7—O14	1.206 (4)
N1—C5	1.466 (4)	C8—O10	1.249 (4)
C2—C8	1.537 (4)	C8—O9	1.259 (3)
C2—C3	1.574 (4)	C11—H11A	0.9800
C2—H2	1.0000	C11—H11B	0.9800
C3—C11	1.523 (4)	C11—H11C	0.9800
C3—C12	1.524 (4)	C12—H12A	0.9800
C3—S4	1.872 (3)	C12—H12B	0.9800
S4—C5	1.820 (3)	C12—H12C	0.9800
C5—C6	1.551 (4)	N13—H13A	0.98 (5)
C5—H5	1.0000	N13—H13B	0.96 (5)
C6—N13	1.469 (4)	N13—H13C	0.90 (4)
C6—C7	1.550 (4)
C7—N1—C2	131.8 (3)	C7—C6—H6	110.8
C7—N1—C5	94.8 (2)	C5—C6—H6	110.8
C2—N1—C5	116.4 (2)	O14—C7—N1	133.5 (3)
N1—C2—C8	109.8 (2)	O14—C7—C6	135.8 (3)
N1—C2—C3	106.2 (2)	N1—C7—C6	90.7 (2)
C8—C2—C3	112.6 (2)	O10—C8—O9	126.0 (3)
N1—C2—H2	109.4	O10—C8—C2	116.7 (2)
C8—C2—H2	109.4	O9—C8—C2	117.3 (2)
C3—C2—H2	109.4	C3—C11—H11A	109.5
C11—C3—C12	110.2 (2)	C3—C11—H11B	109.5
C11—C3—C2	113.9 (2)	H11A—C11—H11B	109.5
C12—C3—C2	109.2 (2)	C3—C11—H11C	109.5
C11—C3—S4	108.8 (2)	H11A—C11—H11C	109.5
C12—C3—S4	108.6 (2)	H11B—C11—H11C	109.5
C2—C3—S4	105.91 (18)	C3—C12—H12A	109.5
C5—S4—C3	94.75 (13)	C3—C12—H12B	109.5
N1—C5—C6	87.3 (2)	H12A—C12—H12B	109.5
N1—C5—S4	104.49 (19)	C3—C12—H12C	109.5
C6—C5—S4	119.68 (19)	H12A—C12—H12C	109.5
N1—C5—H5	113.9	H12B—C12—H12C	109.5
C6—C5—H5	113.9	C6—N13—H13A	110 (3)
S4—C5—H5	113.9	C6—N13—H13B	111 (2)
N13—C6—C7	117.3 (3)	H13A—N13—H13B	111 (3)
N13—C6—C5	120.0 (2)	C6—N13—H13C	107 (3)
C7—C6—C5	84.8 (2)	H13A—N13—H13C	110 (4)
N13—C6—H6	110.8	H13B—N13—H13C	107 (3)
C7—N1—C2—C8	152.5 (3)	C3—S4—C5—C6	109.4 (2)
C5—N1—C2—C8	−82.8 (3)	N1—C5—C6—N13	129.5 (3)
C7—N1—C2—C3	−85.4 (3)	S4—C5—C6—N13	24.3 (4)
C5—N1—C2—C3	39.3 (3)	N1—C5—C6—C7	10.88 (19)
N1—C2—C3—C11	−143.5 (3)	S4—C5—C6—C7	−94.3 (2)
C8—C2—C3—C11	−23.2 (3)	C2—N1—C7—O14	−35.0 (5)
N1—C2—C3—C12	92.9 (3)	C5—N1—C7—O14	−167.3 (4)
C8—C2—C3—C12	−146.8 (2)	C2—N1—C7—C6	144.6 (3)
N1—C2—C3—S4	−23.9 (2)	C5—N1—C7—C6	12.3 (2)
C8—C2—C3—S4	96.4 (2)	N13—C6—C7—O14	46.8 (5)
C11—C3—S4—C5	128.3 (2)	C5—C6—C7—O14	168.0 (4)
C12—C3—S4—C5	−111.7 (2)	N13—C6—C7—N1	−132.8 (2)
C2—C3—S4—C5	5.46 (19)	C5—C6—C7—N1	−11.6 (2)
C7—N1—C5—C6	−12.3 (2)	N1—C2—C8—O10	39.8 (3)
C2—N1—C5—C6	−154.3 (2)	C3—C2—C8—O10	−78.4 (3)
C7—N1—C5—S4	107.7 (2)	N1—C2—C8—O9	−140.7 (2)
C2—N1—C5—S4	−34.3 (3)	C3—C2—C8—O9	101.2 (3)
C3—S4—C5—N1	14.16 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N13—H13A···O10^i	0.98 (4)	1.68 (4)	2.647 (3)	170 (4)
N13—H13B···O9^ii	0.96 (5)	1.79 (5)	2.738 (4)	169 (4)
N13—H13C···O9^iii	0.90 (4)	2.04 (4)	2.825 (3)	145 (4)
N13—H13C···O14^iv	0.90 (4)	2.66 (4)	3.242 (3)	124 (3)
C6—H6···O9^iii	1.00	2.53	3.018 (3)	110

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