Holy Grails for Computational Organic Chemistry and Biochemistry

Abstract

Computational chemistry and biochemistry began with Isaac Newton's classical mechanics in the 17th century and the establishment of quantum mechanics in the 1920s. Enabled by extraordinary advances in computers, in the last half century, this field has become a robust partner with experiment. The challenges facing computational chemists and biochemists, the Holy Grails of the field, are described. These include the development of a highly accurate density functional, ideally one that has universal chemical accuracy, and accurate polarizable force fields, as well as methods to handle efficiently the massive number of computations that must be performed for molecular dynamics and for the computation of flexible systems such as proteins. We estimate when the breakthroughs that will make computation a powerful engine for chemical discovery and design will be achieved. The Holy Grails of this field involve methods to enable the accurate and efficient prediction of structures and properties of complex biological systems and materials. The principal Holy Grail is a routine computational method for the prediction and design of multicomponent, often heterogeneous, functional systems and devices.

Understanding the Reactivity and Selectivity of Fluxional Chiral DMAP‐Catalyzed Kinetic Resolutions of Axially Chiral Biaryls

“…[14][15][16][17][18][19] Studying such reactions computationally not only enriches our understanding of thesep rocesses but also creates opportunities to improvetheir efficiency. [20][21][22][23][24][25][26][27] In continuationo fo ur efforts to understandt he stereoselectivity of organocatalyzed reactions, [29] particularly in the context of KRs, [30,31] we have examined the KR of axially chiral biaryls reported by Sibi and co-workersi n2 014 (Scheme 1). [28] In this reaction, chiral DMAP catalyst A serves as ah ighly selective catalystw hen paired with isobutyric anhydride as the acylating agent.A lthough there have been previousc omputational studieso fo therK Rs of alcohols, [10,[32][33][34][35] the reactioni n Scheme 1p resents an umber of unique features.F irst, it is the seminale xample of an organocatalyzed KR that providese xcellent selectivities for axially chiral alcohols, yet has not been explored computationally.S econd, it exhibits high degreeso fs electivity despite the use of ah ighly-fluxional chiral catalyst.…”

Experimental–Computational Synergy for Selective Pd(II)-Catalyzed C–H Activation of Aryl and Alkyl Groups

“…10,11,12 Computations have become essential to elucidate structures and properties of molecules, and mechanisms and selectivities of reactions. 13 Thanks to the rapid development of hardware, software, and theoretical methods, computational chemistry has evolved to a very powerful and routine tool to study the mechanisms and selectivities of more complex reactions. In this Account, we present several examples of collaboration between experimental and computational researchers that led to advances in understandings and innovative new methods.…”

Computational exploration of Pd‐catalyzed C–H bond activation reactions

“…The establishment of quantum mechanics in the 1920s, and the prosperity of quantum mechanical methods in the 1960s, including Hartree−Fock, post‐Hartree−Fock methods, and density functional theory (DFT)‐based computational methods made computational chemistry as a robust partner with experiment . A brief history of computational chemistry was well described with a timeline in one of Houk's Perspective articles . Computational chemistry has become involved in nearly every area of chemistry.…”

“…[1] A brief history of computational chemistry was well described with a timeline in one of Houk's Perspective articles. [2] Computational chemistry has become involved in nearly every area of chemistry. With the rapid development of computational methods and computer power, we can compute more complex and flexible organic systems.…”