Crystal structure of monoclinic calcium pyro­phosphate dihydrate (m-CPPD) involved in inflammatory reactions and osteoarthritis

Pure monoclinic calcium pyrophosphate dihydrate (m-CPPD) has been synthesized and characterized by synchrotron powder X-ray diffraction and neutron diffraction. Rietveld refinement of complementary diffraction data has, for the first time, allowed the crystal structure of m-CPPD to be solved. The monoclinic system P2₁/n was confirmed and unit-cell parameters determined: a = 12.60842 (4), b = 9.24278 (4), c = 6.74885 (2) Å and β = 104.9916 (3)°. Neutron diffraction data especially have allowed the precise determination of the position of H atoms in the structure. The relationship between the m-CPPD crystal structure and that of the triclinic calcium pyrophosphate dihydrate (t-CPPD) phase as well as other pyrophosphate phases involving other divalent cations are discussed by considering the inflammatory potential of these phases and/or their involvement in different diseases. These original structural data represent a key step in the understanding of the mechanisms of crystal formation involved in different types of arthritis and to improve early detection of calcium pyrophosphate (CPP) phases in vivo.

S1. Experimental

S1.1. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1.

S2. Results and discussion

Computing details

For both compounds, program(s) used to solve structure: TOPAS; program(s) used to refine structure: FULLPROF; molecular graphics: DIAMOND; software used to prepare material for publication: PLATON.

Figures

(XRD) Calcium Pyrophosphate Dihydrate

Crystal data

O7P2·2(H2O)·2(Ca)	Z = 4
Mr = 290.13	Dx = 2.537 Mg m^−3
Monoclinic, P21/n	Synchrotron radiation, λ = 0.724420 Å
Hall symbol: -P 2yn	µ = 2.36 mm^−1
a = 12.60842 (4) Å	T = 291 K
b = 9.24278 (4) Å	Particle morphology: needles
c = 6.74885 (2) Å	white
β = 104.9916 (3)°	cylinder, 25 × 7 mm
V = 759.72 (1) Å^3

Data collection

2-circle diffractometer	Data collection mode: transmission
Radiation source: Cristal beamline, Soleil Synchrotron	Scan method: step
Si(111) crystal monochromator	2θmin = 0.020°, 2θmax = 49.996°, 2θstep = 0.004°

Refinement

Rp = 4.148	Profile function: pseudo-Voigt
Rwp = 5.344	104 parameters
Rexp = 2.079	0 restraints
RBragg = 5.053	H-atom parameters not refined
χ^2 = 6.606	Background function: interpolated
12495 data points	Preferred orientation correction: none

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

	x	y	z	Uiso*/Ueq
Ca1	0.3766 (2)	0.6189 (4)	0.3299 (4)	0.0315 (11)*
Ca2	0.6437 (2)	0.6269 (4)	0.2124 (4)	0.0210 (10)*
O1	0.3590 (5)	0.6195 (10)	0.6714 (9)	0.013 (2)*
O2	0.4571 (5)	0.6486 (9)	1.0491 (10)	0.026 (3)*
O3	0.3352 (6)	0.8528 (11)	0.8419 (11)	0.024 (3)*
O4	0.5685 (5)	0.6421 (9)	0.5156 (10)	0.004 (2)*
O5	0.6953 (5)	0.8431 (9)	0.6968 (10)	0.005 (2)*
O6	0.6610 (6)	0.6109 (10)	0.8757 (10)	0.027 (3)*
O7	0.5169 (6)	0.8007 (5)	0.7804 (11)	0.0151 (18)*
OW1	0.3988 (5)	0.8723 (12)	0.3264 (11)	0.040 (3)*
OW2	0.6273 (5)	0.8774 (12)	0.2648 (11)	0.032 (3)*
P1	0.4078 (3)	0.7232 (6)	0.8397 (6)	0.0261 (12)*
P2	0.6136 (3)	0.7244 (6)	0.7109 (5)	0.0279 (14)*
H1	0.343 (5)	0.934 (7)	0.358 (10)	0.06333*
H2	0.452 (5)	0.905 (7)	0.273 (11)	0.06333*
H3	0.624 (6)	0.980 (9)	0.221 (13)	0.06333*
H4	0.668 (5)	0.909 (5)	0.446 (10)	0.06333*

Geometric parameters (Å, º)

P1—O1	1.492 (9)	Ca1—OW1	2.360 (12)
P1—O2	1.551 (8)	Ca1—O1	2.372 (7)
P1—O3	1.510 (11)	Ca1—O2^ii	2.386 (8)
P1—O7	1.688 (9)	Ca1—O4	2.429 (6)
P2—O4	1.501 (8)	Ca1—O6^iii	2.514 (9)
P2—O5	1.525 (9)	Ca1—O4^iii	2.648 (9)
P2—O6	1.533 (9)	Ca2—O2^ii	2.334 (6)
P2—O7	1.581 (9)	Ca2—O6^ii	2.343 (8)
OW1—H1	0.97 (7)	Ca2—O3^iv	2.353 (8)
OW1—H2	0.89 (7)	Ca2—OW2	2.359 (12)
OW2—H3	0.99 (8)	Ca2—O1^iii	2.412 (10)
OW2—H4	1.23 (6)	Ca2—O4	2.472 (8)
Ca1—O5^i	2.257 (6)
O1—P1—O3	112.7 (6)	O4—P2—O7	109.9 (4)
O1—P1—O2	113.4 (4)	O5—P2—O6	113.3 (5)
O1—P1—O7	107.0 (4)	O5—P2—O7	106.4 (4)
O2—P1—O3	116.4 (5)	O6—P2—O7	106.0 (4)
O2—P1—O7	104.2 (4)	P1—O7—P2	128.3 (5)
O3—P1—O7	101.5 (4)	H4—OW2—H3	93 (5)
O4—P2—O5	114.7 (5)	H2—OW1—H1	123 (6)
O4—P2—O6	106.2 (4)
O3—P1—P2—O5	22.7 (7)	O6—P1—P2—O2	−16.7 (5)
O1—P1—P2—O4	9.3 (5)

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

(neutrondiffraction) Calcium Pyrophosphate Dihydrate

Crystal data

O7P2·2(H2O)·2(Ca)	Z = 4
Mr = 290.13	under primary vacuum
Monoclinic, P21/n	Dx = 2.552 Mg m^−3
Hall symbol: -P 2yn	Constant Wavelength Neutron Diffraction radiation, λ = 2.423000 Å
a = 12.5840 (14) Å	T = 291 K
b = 9.2184 (10) Å	Particle morphology: needles
c = 6.7372 (7) Å	white
β = 104.949 (11)°	cylinder, 50 × 8 mm
V = 755.09 (15) Å^3

Data collection

Linear multidetector diffractometer	Scan method: continuous
Radiation source: nuclear reactor, PYRRHIAS diffractometer Orphee reactor	2θmin = 7.019°, 2θmax = 86.919°, 2θstep = 0.100°
Data collection mode: transmission

Refinement

Rp = 1.417	Profile function: pseudo-Voigt
Rwp = 1.964	104 parameters
Rexp = 0.891	0 restraints
RBragg = 6.903	Only H-atom coordinates refined
χ^2 = 4.857	Background function: interpolated
800 data points	Preferred orientation correction: none

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

	x	y	z	Uiso*/Ueq
Ca1	0.3766 (2)	0.6189 (4)	0.3299 (4)	0.01267*
Ca2	0.6437 (2)	0.6269 (4)	0.2124 (4)	0.01267*
O1	0.3590 (5)	0.6195 (10)	0.6714 (9)	0.01267*
O2	0.4571 (5)	0.6486 (9)	1.0491 (10)	0.01267*
O3	0.3352 (6)	0.8528 (11)	0.8419 (11)	0.01267*
O4	0.5685 (5)	0.6421 (9)	0.5156 (10)	0.01267*
O5	0.6953 (5)	0.8431 (9)	0.6968 (10)	0.01267*
O6	0.6610 (6)	0.6109 (10)	0.8757 (10)	0.01267*
O7	0.5169 (6)	0.8007 (5)	0.7804 (11)	0.01267*
OW1	0.3988 (5)	0.8723 (12)	0.3264 (11)	0.01267*
OW2	0.6273 (5)	0.8774 (12)	0.2648 (11)	0.01267*
P1	0.4078 (3)	0.7232 (6)	0.8397 (6)	0.01267*
P2	0.6136 (3)	0.7244 (6)	0.7109 (5)	0.01267*
H1	0.343 (5)	0.934 (7)	0.358 (10)	0.01267*
H2	0.452 (5)	0.905 (7)	0.273 (11)	0.01267*
H3	0.624 (6)	0.980 (9)	0.221 (13)	0.01267*
H4	0.668 (5)	0.909 (5)	0.446 (10)	0.01267*