Realizing functionality encoded molecular architectures at defined interfaces has always been a challenging task. Controlling, disassembling, and altering H-bonds is of critical importance in the design of functional two-dimensional (2D) materials. Using H-bonding as the driving interaction, the following strategies were adopted in achieving the desired architectures: • Dimensionality dictated H-bond reorganization at the air-water interface. • Formulation of active template strategy using well defined self-assembled monolayers for inducing H-bond reorganization. • Design of multicomponent smart organic interfaces endowed with H-bond acceptors following H-bond assisted molecular recognition at the solid-liquid interface. Molecular conformation and packing restrictions in the Langmuir and self-assembled monolayers have been found to be the bottlenecks in controlling and reorganizing the H-bonds. This chapter details the diversity-driven bold design and mechanistic report, adopting both experiments and computations, on the 2D orientation-specific molecular ellipsoids conceived from a single component benzoic acid based amphiphile, drawing attention to rules centering around monomer structure, intra and intermolecular twists and the only 2D degree of freedom, the surface pressure, directing shape anisotropy during the dynamic self-assembly. The importance of chirality and recognition through chemical specificity and surface sensitive vibrational spectroscopy was used extensively as a label-free approach for investigating biomembrane behavior. Enantio-selective molecular recognition of Phenylalanine by the anisotropic 2D DPPC lipid membrane was explored. By adopting polarized FT-IRRAS spectroscopy in conjunction with static and dynamic ab initio computational studies, a molecular level understanding of the enantioselective binding of the D-enantiomer over its L-enantiomer was established. Hydration played a key role in the binding affinity, and the specificity of amino acid-lipid interaction altered the IRRAS frequency and intensity to differing degrees, enabling them to be distinguished. The work exemplified the significant role of water in mediating intermolecular amino acid-lipid interaction. Methodical access to a wide range of geometrical assembles encompassing all the dimensions of a strained structural Oxanorbornane framework at A/W interface as well as in the bulk was demonstrated. Amphiphilic oxanorbornane skeletal frame efficiently organized to direct the formation of dimensionally controllable, geometry-specific nanostructures as diverse as 0D surface/reverse micelles, 1D nanofibers, 2D rectangular/square sheets, and 3D flowers. The racemate with its precise stereo-projection of the -OH groups and the ring oxygen catered towards Li+ ion sensing and aided in the formation of pre-micellar aggregates of conventional surfactants. © 2019 Elsevier Inc. All rights reserved.