Designing Molecules by Optimizing Potentials

Abstract

The astronomical number of accessible discrete chemical structures makes rational molecular design extremely challenging. We formulate the design of molecules with specific tailored properties as performing a continuous optimization in the space of electron-nuclear attraction potentials. The optimization is facilitated by using a linear combination of atomic potentials (LCAP), a general framework that creates a continuous property landscape from an otherwise unlinked set of discrete molecular-property values. A demonstration of this approach is given for the optimization of molecular electronic polarizability and hyperpolarizability. We show that the optimal structures can be determined without enumerating and separately evaluating the characteristics of the combinatorial number of possible structures, a process that would be much slower. The LCAP approach may be used with quantum or classical Hamiltonians, suggesting possible applications to drug design and new materials discovery.

First principles view on chemical compound space: Gaining rigorous atomistic control of molecular properties

“…Albeit mixing up spatial and compositional degrees of freedom, this is more in line with conventional thought in quantum chemistry and conceptual DFT [15] where the nuclear charge distribution is hardly ever mentioned explicitly. The route via the external potential has been pursued within the Ansatz of linear combination of atomic potentials in the research groups of Yang and Beratan, [50] assigning atom-type specific weights to every atom site. Using simplified Hamiltonians, impressive results were obtained for the control of molecular hyperpolarizabilities, [51][52][53][54][55] furthering long-standing molecular design efforts for electronic properties well ahead of their time.…”

“…Or if Z I is a combination of various atom-types, in line with the aforementioned linear combination of atomic potentials approach, [50] the weight of one nuclear charge has to dominate so that it can safely be increased to 1, while decreasing all others to zero. Furthermore, constraints due to overall charge conservation, and electronic structure, have to be taken into account.…”

Accelerating self-consistent field convergence with the augmented Roothaan–Hall energy function

“…[3][4][5][6][7] Because of the good balance between computational cost and desired accuracy, KohnSham ͑KS͒ density functional theory ͑KS-DFT͒, 8,9 based on a single Slater determinant, is a very popular method to describe the electronic structures of molecules or materials. In both Hatree-Fock and KS approaches, the self-consistent field ͑SCF͒ scheme is applied to obtain the total energies of systems.…”

Accelerated computational discovery of high-performance materials for organic photovoltaics by means of cheminformatics

“…Developments in cheminformatics have been driven by the combination of experimental high-throughput screening (the assay and analysis of more than a million chemical reactions) and with the ability to computationally predict physicochemical parameters (called descriptors). The basic strategy of this approach is to obtain these descriptors for candidate molecules, often obtained from designated candidate libraries, [72][73][74][75][76][77][78][79][80] to score their fitness with respect to a desired set of properties.…”