A gradient-directed Monte Carlo approach to molecular design.

The recently developed linear combination of atomic potentials (LCAP) approach [M. Wang et al., J. Am. Chem. Soc. 128, 3228 (2006)] allows continuous optimization in a discrete chemical space, and thus is useful in the design of molecules for targeted properties. To address further challenges arising from the rugged, continuous property surfaces in the LCAP approach, we develop a gradient-directed Monte Carlo (GDMC) strategy as an augmentation to the original LCAP optimization method. The GDMC method retains the power of exploring molecular space by utilizing local gradient information computed from the LCAP approach to jump between discrete molecular structures. It also allows random MC moves to overcome barriers between local optima on property surfaces. The combined GDMC-LCAP approach is demonstrated here for optimizing nonlinear optical properties in a class of donor-acceptor substituted benzene and porphyrin frameworks. Specifically, one molecule with four nitrogen atoms in the porphyrin ring was found to have a larger first hyperpolarizability than structures with the conventional porphyrin motif.

[1]  A. Zunger,et al.  Self-interaction correction to density-functional approximations for many-electron systems , 1981 .

[2]  Shahar Keinan,et al.  Designing molecules with optimal properties using the linear combination of atomic potentials approach in an AM1 semiempirical framework. , 2007, The journal of physical chemistry. A.

[3]  D. Vanderbilt,et al.  Soft self-consistent pseudopotentials in a generalized eigenvalue formalism. , 1990, Physical review. B, Condensed matter.

[4]  K. Suslick,et al.  Push-pull Porphyrins as Nonlinear Optical Materials , 1992 .

[5]  K. Dill,et al.  A lattice statistical mechanics model of the conformational and sequence spaces of proteins , 1989 .

[6]  D. Yee,et al.  Principles of protein folding — A perspective from simple exact models , 1995, Protein science : a publication of the Protein Society.

[7]  Mark A. Ratner,et al.  Design and construction of molecular assemblies with large second-order optical nonlinearities. Quantum chemical aspects , 1994 .

[8]  G. K. Ananthasuresh,et al.  A Quadratic Programming Formulation for the Design of Reduced Protein Models in Continuous Sequence Space , 2005 .

[9]  E. M. Graham,et al.  The electronic structure and second-order nonlinear optical properties of donor-acceptor acetylenes: a detailed investigation of structure-property relationships , 1991 .

[10]  Seth R. Marder,et al.  Stronger acceptors can diminish nonlinear optical response in simple donor-acceptor polyenes , 1993 .

[11]  C. Dobson.  Chemical space and biology , 2004, Nature.

[12]  Alex Zunger,et al.  Finding the atomic configuration with a required physical property in multi-atom structures , 2007, Journal of physics. Condensed matter : an Institute of Physics journal.

[13]  K. Dill,et al.  ‘‘Sequence space soup’’ of proteins and copolymers , 1991 .

[14]  Weitao Yang,et al.  Designing molecules by optimizing potentials. , 2006, Journal of the American Chemical Society.

[15]  D. Dudis,et al.  Quantum Mechanical Methods for Predicting Nonlinear Optical Properties , 2007 .

[16]  R. C. Miller,et al.  New transitions in the photoluminescence of GaAs quantum wells , 1981 .

[17]  Dequan Xiao,et al.  Inverse molecular design in a tight-binding framework. , 2008, The Journal of chemical physics.

[18]  Seth R. Marder,et al.  Electric Field Modulated Nonlinear Optical Properties of Donor-Acceptor Polyenes: Sum-Over-States Investigation of the Relationship between Molecular Polarizabilities (.alpha., .beta., and .gamma.) and Bond Length Alternation , 1994 .

[19]  A. Hopkins,et al.  Navigating chemical space for biology and medicine , 2004, Nature.

[20]  Alex Zunger,et al.  The inverse band-structure problem of finding an atomic configuration with given electronic properties , 1999, Nature.

[21]  Kenneth D. Singer,et al.  Exceptional second‐order nonlinear optical susceptibilities of quinoid systems , 1981 .

[22]  H. Scheraga,et al.  Global optimization of clusters, crystals, and biomolecules. , 1999, Science.

[23]  S. Marder,et al.  SYNTHESES AND LINEAR AND NONLINEAR OPTICAL PROPERTIES OF UNSYMMETRICAL SQUARAINES WITH EXTENDED CONJUGATION , 1994 .

[24]  Seth R. Marder,et al.  Experimental investigations of organic molecular nonlinear optical polarizabilities. 2. A study of conjugation dependences , 1991 .

[25]  D. Beratan,et al.  Approaches for Optimizing the First Electronic Hyperpolarizability of Conjugated Organic Molecules , 1991, Science.

[26]  James J. P. Stewart,et al.  Calculation of the nonlinear optical properties of molecules , 1990 .

[27]  Seth R. Marder,et al.  Experimental investigations of organic molecular nonlinear optical polarizabilities. 1. Methods and results on benzene and stilbene derivatives , 1991 .

[28]  M. Ratner,et al.  Electronic Structure and Quadratic Hyperpolarizabilities in Organotransition-Metal Chromophores Having Weakly Coupled .pi.-Networks. Unusual Mechanisms for Second-Order Response , 1994 .

[29]  Mark A. Ratner,et al.  Molecular and Macromolecular Nonlinear Optical Materials. Probing Architecture/Electronic Structure/Frequency Doubling Relationships via an SCF-LCAO MECI π Electron Formalism , 1988 .

[30]  I. Kuntz,et al.  Structure-Based Molecular Design , 1994 .

[31]  Ursula Rothlisberger,et al.  Variational particle number approach for rational compound design. , 2005, Physical review letters.

[32]  David M. Ceperley,et al.  Fixed-node quantum Monte Carlo for molecules , 1982 .

[33]  T. K. Chandrashekar,et al.  Modified push-pull expanded corroles: Syntheses, structure and nonlinear optical properties , 2005 .

[34]  Mark A. Ratner,et al.  Electron donor-acceptor complexes as potential high-efficiency second-order nonlinear optical materials. A computational investigation , 1993 .

[35]  Peter Ertl,et al.  Cheminformatics Analysis of Organic Substituents: Identification of the Most Common Substituents, Calculation of Substituent Properties, and Automatic Identification of Drug-like Bioisosteric Groups , 2003, J. Chem. Inf. Comput. Sci..

[36]  Christoph Kuhn,et al.  Inverse Strategies for Molecular Design , 1996 .

[37]  W. L. Jorgensen.  The Many Roles of Computation in Drug Discovery , 2004, Science.

[38]  G. K. Ananthasuresh,et al.  A Deterministic Optimization Approach to Protein Sequence Design Using Continuous Models , 2005, Int. J. Robotics Res..

[39]  Manish Sinha,et al.  On the Solution of Mixed-integer Nonlinear Programming Models for Computer Aided Molecular Design , 2002, Comput. Chem..

[40]  J. Brédas,et al.  Donor-acceptor diphenylacetylenes : geometric structure, electronic structure, and second-order nonlinear optical properties , 1993 .