Molecular electrostatic potential (MESP) topology analysis reveals the underlying phenomenon of the through-space effect (TSE), which imparts electron donor-acceptor properties to a wide range of chemical systems, including derivatives of pyrrole, indole, isoindole, azulene, and aniline. The TSE is inherent in pyrrole owing to the strong polarization of electron density (PoED) from the formally positively charged N-center to the C3C4 bonding region. The N → C3C4 directional nature of the TSE has been effectively employed to design molecules with high electronic polarization, such as bipyrroles, polypyrroles, phenyl pyrroles, multi-pyrrolyl systems and N-doped nanographenes. In core-expanded structures, the direction of electron flow from pyrrole units towards the core leads to highly electron-rich systems, while the opposite arrangement results in highly electron-deficient systems. Similarly, the MESP analysis reveals the presence of the TSE in azulene, indole, isoindole, and aniline. Oligomeric chains of these systems are designed in such a way that the direction of electron flow is consistent across each monomer, leading to substantial electronic polarization between the first and last monomer units. Notably, these designed systems exhibit strong donor-acceptor characteristics despite the absence of explicit donor and acceptor moieties, which is supported by FMO analysis, APT charge analysis, NMR data and λmax data. Among the systems studied, the TSEs of many experimentally known systems (bipyrroles, phenyl pyrroles, hexapyrrolylbenzene, octapyrrolylnaphthalene, decapyrrolylcorannulene, polyindoles, polyazulenes, etc.) are unraveled for the first time, while numerous new systems (polypyrroles, polyisoindoles, and amino-substituted benzene polymers) are predicted to be promising materials for the creation of donor-acceptor systems. These findings demonstrate the potential of the TSE in molecular design and provide new avenues for creating functional materials.