The pharmaceutical carvedilol acts as a nonselective beta(beta(1)/beta(2)) and selective alpha(alpha(1)) adrenoceptor antagonist, cardioprotector, antioxidant, oxidative phosphorylation uncoupler, and amyloid-beta (Abeta) antifibrillar agent. Given these diverse pharmacodynamic profiles, the resolution of carvedilol's highly populated conformations are necessary to divulge the basis of its interactions with these molecular targets. However, given carvedilol's sizable conformational hypersurface (11 torsional angles and 3(11) conformational possibilities), this task is preferentially achieved by means of a novel rational molecular fragmentation method to minimize computational and experimental resources. Presently we have isolated and optimized nine low energy carvedilol conformers with high level B3LYP/6-31G(d) density functional theory (DFT with the Becke 3LYP hybrid exchange-correlation functional) molecular orbital computations in the gas phase and in the solvent phase (DMSO and water) with Onsager solvent reaction field calculations as a means to arrive at the uncharacterized low energy structures and solvent effect of carvedilol. Additionally, carvedilol has been analyzed with NMR spectroscopy (in DMSO) to correlate theoretical- and experimental-derived electronic structure. Gas phase results show that seven of the nine conformers possess a novel tetracentric spiro-type conformation composed of intramolecular six- and eight-membered rings. This structural motif is dictated by the necessary stabilization of the positively charged nitrogen group and by the inflexibility of the carbazole aromatic ring. DMSO and water DFT optimizations and NMR spectroscopy closely mirror each other indicating that carvedilol has a subtle energetic and structural solvent effect. ROESY and scalar coupling show further evidence of the rigid rotation about the large carbazole pharmacophore. Given the harmony achieved between theoretical and experimental results, this study suggests the most populated states of carvedilol expected to dominate physical and biological samples and gives credence to the ability of methodically analyzing complex molecular systems by means of theoretical structure-activity fragmentation. Together, this will critically aid the molecular understating of carvedilol's pharmacodynamic mechanisms and structural underpinnings.