X-ray multiple diffraction has been applied to study the substitutional incorporation of Mg 2+ ions into NSH crystals (nickel sulfate hexahydrate, NiSO 4 Á6H 2 O). Intensity profiles provide information on invariant phases, while angular positions of the multiple diffractions allow accurate determination of lattice parameters. By increasing the atomic disordering only of O 2À sites in model structures of doped NSH, the sense and magnitude of induced phase shifts match those necessary to justify the observed changes in the intensity profiles. Causes of disordering and lattice parameter variation are discussed. Although the amount of extra oxygen disordering is relatively large with respect to the small difference in the ionic radii of the metallic ions, this disordering is beyond the resolution power achievable by analyzing diffracted intensities of isolated reflections, such as in standard crystallographic techniques.

A pair of enantiomer crystals is used to demonstrate how X-ray phase measurements provide reliable information for absolute identification and improvement of atomic model structures. Reliable phase measurements are possible thanks to the existence of intervals of phase values that are clearly distinguishable beyond instrumental effects. Because of the high susceptibility of phase values to structural details, accurate model structures were necessary for succeeding with this demonstration. It shows a route for exploiting physical phase measurements in the crystallography of more complex crystals.

From inorganic crystals to macromolecular crystals, structure determination with atomic resolution is based on diffraction techniques (electrons, X-rays and neutrons). However, since the coherent scattering cross-section for X-rays by atoms have intermediate values between those for electrons and neutrons, experimental measurements of the phases of structure factors are feasible only for X-rays. Unprecedented results [1-3] have show how phase measurements can reveal important information of the crystalline structure of doped crystals, which are inaccessible by other techniques: "differently from any other method in X-ray crystallography based on structure refinement of intensity data, the presented method pinpoint a specific feature of the structure and directly prove its existence beyond of any reliability parameter or of goodness-of-fitting value." Although there are instrumental and computational challenges, the method can be extended to protein crystallography for improving resolution of poorly solved features of the structures. As depicted in Fig. 1, the structure factor of a given reflection has contributions of distinct groups of atoms. Low resolution at one group can result in phase deviation of Fickle, without significantly affecting its amplitude. For instance, small differences in the symmetry of charge balance at group B can cause great difference in the phase angle of this group, which increases the phase angle of Fickle, Fig. 1 (b). On the other hand, reduction in the scattering amplitude of group E due to atomic disordering decreases the phase angle, Fig. 1 (c). In this presentation, we discuss the current understanding of this method, its perspectives, and importance of providing a tool for structural analysis of macromolecules that is able to go beyond the resolution achieved by the techniques actually in use.