Despite the worldwide public health impact of malaria, neither the mechanism by which the Plasmodium parasite detoxifies and sequesters haem, nor the action of current antimalarial drugs is well understood. The haem groups released from the digestion of the haemoglobin of infected red blood cells are aggregated into an insoluble material called haemozoin or malaria pigment. Synthetic beta-haematin (FeIII-protoporphyrin-IX)2 is chemically, spectroscopically and crystallographically identical to haemozoin and is believed to consist of strands of FeIII-porphyrin units, linked into a polymer by propionate oxygen-iron bonds. Here we report the crystal structure of beta-haematin determined using simulated annealing techniques to analyse powder diffraction data obtained with synchrotron radiation. The molecules are linked into dimers through reciprocal iron-carboxylate bonds to one of the propionic side chains of each porphyrin, and the dimers form chains linked by hydrogen bonds in the crystal. This result has implications for understanding the action of current antimalarial drugs and possibly for the design of new therapeutic agents.

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The reaction of [M II (OH 2 ) 6 ](NO 3 ) 2 (M ) Co, Ni) and [N(CN) 2 ]leads to formation of isomorphous M[N(CN) 2 ] 2 [M ) Co (2a), Ni (3)], respectively, while the reaction of [Co II (OH 2 ) 6 ]-(NO 3 ) 2 in 1% pyridine (py) solution with [N(CN) 2 ]leads to the formation of Co[N(CN) 2 ] 2 py 2 . The structure of 2a, R-Co[N(CN) 2 ] 2 , was determined from the Rietveld analyses of both powder X-ray (synchrotron) and neutron as well as single-crystal X-ray diffraction data, whereas the structure of 3 was determined from the Rietveld analysis of powder neutron diffraction data. 2a (pink) and 3 (light blue) belong to the orthorhombic space group Pnnm with Z ) 2 [2a (single crystal): a ) 5.9985(15), b ) 7.0711(18), c ) 7.4140(19) Å, V ) 314.47(14) Å 3 , R 1 ) 0.027. 3 (powder neutron diffraction): a ) 5.97357(25), b ) 7.03196(28), c ) 7.29424(22) Å, V ) 306.40(3) Å 3 , χ 2 ) 1.650]. Thermolysis of Co[N(CN) 2 ] 2 py 2 leads to intensely blue β-Co II [N(CN) 2 ] 2 , 2b. The M in 2a and 3 are six-coordinate and bound to six different µ 3 -bonded [N(CN) 2 ]ligands, forming a rutile-like 3-D framework. Both M II sites are slightly tetragonally elongated, with average axial M-N distances (295 K) of 2.161(5) (2a) and 2.137(2) Å ( 3) and average equatorial M-N distances of 2.091(4) (2a) and 2.051(1) Å (3), and each M II is coordinated to four equatorial [N(CN) 2 ]ligands that bridge between two adjacent M II sites, generating ribbon-like 1-D chains that propagate along the c-axis. Adjacent chains pack out-of-registry, with the central N2s bridging to M II ions of adjacent chains, forming a 3-D network. [N(CN) 2 ]has pseudo-C 2v symmetry with average C1tN1 distances of 1.158 (2a) and 1.159 Å (3) at room temperature and C1-N2 distances of 1.315 (2a) and 1.313 Å (3). The structure of 2b has not yet been elucidated, but on the basis of the color and magnetic properties, it is thought to be comprised of tetrahedral Co(II). The shortest M‚‚‚M separations are 5.936 (2a) and 5.881 Å (3) at room temperature via neutron diffraction studies. The susceptibility for 2a, 2b, and 3 can be fit by the Curie-Weiss expression with g ) 2.60, θ ) 9 K (T > 50 K); g ) 2.27, θ ) -7 K (T > 60 K); and g ) 2.20, θ ) 21 K (T > 50 K), respectively. The observed room-temperature effective moments of 5.13, 4.37, and 3.17 µ B , respectively, exceed the spin-only moments as expected for these metal ions, but are consistent with octahedral Co(II), tetrahedral Co(II), and octahedral Ni-(II), respectively. Ferromagnetic behavior is suggested for 2a and 3 from the 5 K, 5.5 T saturation magnetizations of 14 000 (2a) and 11 900 emu Oe/mol (3), hysteresis loops with coercive fields, H cr , of 800 (2a), 680 (2b), and 7000 Oe (3) at 2 K, field-cooled and zero-fieldcooled low-field M(T) data showing magnetic ordering below essentially magnetic fieldindependent bifurcation temperatures of 9.2 (2a) and 20.6 K (3), and observations of both in-phase, χ′(T), and out-of-phase, χ′′(T), components of the ac susceptibility maxima slightly below the bifurcation temperatures. The...