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X-ray single crystal diffraction is one of the most common and leading methods in materials research, mastery of the subject is essential. This is particularly true for beginners of X-ray crystallography. This book entitled "X-ray crystallographic investigations of significant chalcone derivatives" presents the systematic structural investigations on significant novel chalcone derivatives using single crystal X-Ray diffraction technique. Chalcone moiety (1,3-diaryl-2-propen-1-ones) is the backbone of several antinuclear, cardiovascular and antispasmodic drugs. These groups of compounds constitute an important class of natural products belonging to the flavonoid family and its derivatives have attracted particular interest in medicine during the last few decades. Few chalcone derivatives with significant halogen, hydroxy and methoxy moieties substituted at different sites at (4, 5-dimethoxy-2-methyl-phenyl) prop-2-en-1-one are picked up for X-ray crystallographic investigations.