AI-DRIVEN PHARMACEUTICAL CHEMISTRY: INTEGRATING COMPUTATIONAL DRUG DESIGN, GREEN SYNTHESIS, AND MOLECULAR INNOVATION FOR NEXT-GENERATION THERAPEUTICS

Abstract

Artificial Intelligence (AI) is redefining pharmaceutical chemistry by integrating computational drug design, green synthetic methodologies, and molecular innovation into a unified framework for next-generation therapeutics. Traditional pharmaceutical chemistry relies heavily on iterative synthesis, empirical structure–activity relationship (SAR) studies, and resource-intensive experimental workflows. These approaches are often limited by time constraints, environmental burden, and inefficiencies in exploring large chemical spaces. AI-driven pharmaceutical chemistry introduces a paradigm shift by enabling predictive modeling of molecular properties, automated reaction optimization, retrosynthetic planning, and environmentally sustainable synthesis design. Machine learning (ML), deep learning (DL), and generative models facilitate rapid identification of lead compounds, while quantum-inspired computational tools enhance accuracy in molecular interaction predictions. Additionally, AI-guided green chemistry strategies optimize reaction pathways to minimize hazardous reagents, energy consumption, and waste generation. The integration of AI with green synthesis is particularly significant, as it supports sustainable pharmaceutical development aligned with global environmental goals. Molecular innovation is further accelerated through de novo drug design systems that generate novel scaffolds with optimized pharmacokinetic and pharmacodynamic profiles. Despite these advancements, challenges such as data scarcity, reaction prediction uncertainty, scalability limitations, and lack of standardized green chemistry datasets remain. This review critically explores the convergence of AI, pharmaceutical chemistry, and sustainable synthesis, highlighting current applications, technological frameworks, limitations, and future directions. Overall, AI-driven pharmaceutical chemistry represents a transformative shift toward intelligent, sustainable, and highly efficient drug discovery and development systems.