Weak interactions in crystal engineering : insignts from X-ray diffraction, experimental charge densities and statistical analysis of cambridge structural database

Abstract

Weak Interactions in Crystal Engineering: Insights from X-ray Diffraction, Experimental Charge Densities and Statistical Analysis of Cambridge Structural Database

Overview This thesis consists of six chapters focusing on noncovalent interactions such as ··· , C-H···O, and C-H···F, with special emphasis on fluorine-involving interactions. The work combines X-ray diffraction, experimental charge density analysis, and statistical evaluation using the Cambridge Structural Database (CSD). Geometrical criteria (distance and angle) and topological properties (critical points, bond paths, Laplacian of charge density) are employed to characterize intra- and intermolecular interactions.

Chapter Summaries Chapter 1 Introduces the fundamentals of crystal engineering and the role of noncovalent interactions in supramolecular design. Methodologies for studying weak interactions are outlined, along with a general protocol for the thesis.

Chapter 2 Reports the crystal structure of Ciprofloxacin Lactate using X-ray diffraction.

Structure features channels generated by -stacking, with hydrogen-bonded networks of lactate and water molecules running along the b axis.

Intramolecular C-H···F interaction is observed.

A CSD survey of the 7-piperazin-1-oyl-quinolin-4(1H)-one moiety shows a tendency to form channels via ··· interactions.

Chapter 3 Examines weak interactions in drugs and intermediates.

Haloperidol shows short F···F interactions but no Cl···Cl interactions.

Flunazirine exhibits C-H··· and C-H···F interactions, generating distinct packing patterns.

Comparative studies of benzodiazepinone drugs reveal that fluorine substitution significantly alters packing modes.

Chapter 4 Analyzes p-nitrophenolic twin chromophoric compounds with polymethylene spacers.

Even-numbered spacers crystallize in centrosymmetric space groups, odd-numbered in non-centrosymmetric groups.

C-H···O interactions dominate, with graph-set analysis showing ring (R) patterns in even-series and discrete (D) patterns in odd-series.

Chapter 5 Focuses on 5-fluorouracil (FU) and 1,3-dimethyl-5-fluorouracil (DMFU) using charge density analysis at 100 K.

FU packing is dominated by N-H···O and C-H···O interactions.

DMFU packing involves C-H···O and C-H···F interactions, with methyl substitution eliminating stronger N-H···O bonds.

Topological analysis confirms the contribution of weaker C-H···F interactions to crystal stability.

Chapter 6 Presents a statistical study of C-X··· interactions (X = F, Cl, Br, I) using CSD data.

Distance-angle criteria reveal directional preferences in packing.

Fluorine shows the highest propensity for forming C-X··· interactions compared to other halogens.

Conclusions The thesis provides a comprehensive picture of weak interactions in organic molecular crystals, particularly those involving fluorine. It demonstrates how these interactions influence molecular packing, supramolecular design, and crystal engineering strategies.