A new density functional (DF) of the generalized gradient approximation (GGA) type for general chemistry applications termed B97-D is proposed. It is based on Becke's power-series ansatz from 1997 and is explicitly parameterized by including damped atom-pairwise dispersion corrections of the form C(6) x R(-6). A general computational scheme for the parameters used in this correction has been established and parameters for elements up to xenon and a scaling factor for the dispersion part for several common density functionals (BLYP, PBE, TPSS, B3LYP) are reported. The new functional is tested in comparison with other GGAs and the B3LYP hybrid functional on standard thermochemical benchmark sets, for 40 noncovalently bound complexes, including large stacked aromatic molecules and group II element clusters, and for the computation of molecular geometries. Further cross-validation tests were performed for organometallic reactions and other difficult problems for standard functionals. In summary, it is found that B97-D belongs to one of the most accurate general purpose GGAs, reaching, for example for the G97/2 set of heat of formations, a mean absolute deviation of only 3.8 kcal mol(-1). The performance for noncovalently bound systems including many pure van der Waals complexes is exceptionally good, reaching on the average CCSD(T) accuracy. The basic strategy in the development to restrict the density functional description to shorter electron correlation lengths scales and to describe situations with medium to large interatomic distances by damped C(6) x R(-6) terms seems to be very successful, as demonstrated for some notoriously difficult reactions. As an example, for the isomerization of larger branched to linear alkanes, B97-D is the only DF available that yields the right sign for the energy difference. From a practical point of view, the new functional seems to be quite robust and it is thus suggested as an efficient and accurate quantum chemical method for large systems where dispersion forces are of general importance.

Semiempirical GGA-type density functional constructed with a long-range dispersion correction.

Molecular structure does not easily identify the intricate noncovalent interactions that govern many areas of biology and chemistry, including design of new materials and drugs. We develop an approach to detect noncovalent interactions in real space, based on the electron density and its derivatives. Our approach reveals the underlying chemistry that compliments the covalent structure. It provides a rich representation of van der Waals interactions, hydrogen bonds, and steric repulsion in small molecules, molecular complexes, and solids. Most importantly, the method, requiring only knowledge of the atomic coordinates, is efficient and applicable to large systems, such as proteins or DNA. Across these applications, a view of nonbonded interactions emerges as continuous surfaces rather than close contacts between atom pairs, offering rich insight into the design of new and improved ligands.

/pdf/revealing-noncovalent-interactions-1oqknfvmfi.pdf

Revealing noncovalent interactions.

Combined quantum-mechanics/molecular-mechanics (QM/MM) approaches have become the method of choice for modeling reactions in biomolecular systems. Quantum-mechanical (QM) methods are required for describing chemical reactions and other electronic processes, such as charge transfer or electronic excitation. However, QM methods are restricted to systems of up to a few hundred atoms. However, the size and conformational complexity of biopolymers calls for methods capable of treating up to several 100,000 atoms and allowing for simulations over time scales of tens of nanoseconds. This is achieved by highly efficient, force-field-based molecular mechanics (MM) methods. Thus to model large biomolecules the logical approach is to combine the two techniques and to use a QM method for the chemically active region (e.g., substrates and co-factors in an enzymatic reaction) and an MM treatment for the surroundings (e.g., protein and solvent). The resulting schemes are commonly referred to as combined or hybrid QM/MM methods. They enable the modeling of reactive biomolecular systems at a reasonable computational effort while providing the necessary accuracy.

QM/MM Methods for Biomolecular Systems

Dispersion corrections to standard Kohn–Sham density functional theory (DFT) are reviewed. The focus is on computationally efficient methods for large systems that do not depend on virtual orbitals or rely on separated fragments. The recommended approaches (van der Waals density functional and DFT-D) are asymptotically correct and can be used in combination with standard or slightly modified (short-range) exchange–correlation functionals. The importance of the dispersion energy in intramolecular cases (conformational problems and thermochemistry) is highlighted. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 211-228 DOI: 10.1002/wcms.30

Density functional theory with London dispersion corrections

Introduction
PaDEL-Descriptor is a software for calculating molecular descriptors and fingerprints. The software currently calculates 797 descriptors (663 1D, 2D descriptors, and 134 3D descriptors) and 10 types of fingerprints. These descriptors and fingerprints are calculated mainly using The Chemistry Development Kit. Some additional descriptors and fingerprints were added, which include atom type electrotopological state descriptors, McGowan volume, molecular linear free energy relation descriptors, ring counts, count of chemical substructures identified by Laggner, and binary fingerprints and count of chemical substructures identified by Klekota and Roth.

Methods
PaDEL-Descriptor was developed using the Java language and consists of a library component and an interface component. The library component allows it to be easily integrated into quantitative structure activity relationship software to provide the descriptor calculation feature while the interface component allows it to be used as a standalone software. The software uses a Master/Worker pattern to take advantage of the multiple CPU cores that are present in most modern computers to speed up calculations of molecular descriptors.

Results
The software has several advantages over existing standalone molecular descriptor calculation software. It is free and open source, has both graphical user interface and command line interfaces, can work on all major platforms (Windows, Linux, MacOS), supports more than 90 different molecular file formats, and is multithreaded.

Conclusion
PaDEL-Descriptor is a useful addition to the currently available molecular descriptor calculation software. The software can be downloaded at http://padel.nus.edu.sg/software/padeldescriptor. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcc.21707

PaDEL‐descriptor: An open source software to calculate molecular descriptors and fingerprints

Although the encouraging antitumor activity of [PtCl2(cis-1,4-DACH)] (1; DACH = diaminocyclohexane) was shown in early studies almost 20 years ago, the compound has remained nearly neglected. In contrast, oxaliplatin, containing isomeric 1R,2R-DACH carrier ligand, enjoys worldwide clinic application as a most important therapeutic agent in the treatment of colorectal cancer. By extending the investigation to human chemo-resistant cancer cells, we have demonstrated the real effectiveness of 1 in circumventing cisplatin and oxaliplatin resistance in LoVo colon cancer cells. The uptake of compound 1 by the latter cells was similar to that of sensitive LoVo cells. This is not the case for all other compounds considered in this investigation. Interaction with ds-DNA, investigated by a biosensor assay and by QM/MM geometry optimization of the 1,2-GG intrastrand cross-link, does not show significant differences between 1 and oxaliplatin. However, the DNA adducts of 1 are removed from repair systems with lower efficiency and are more effective in inhibiting DNA and RNA polymerase.

Revisiting [PtCl2(cis-1,4-DACH)]: an underestimated antitumor drug with potential application to the treatment of oxaliplatin-refractory colorectal cancer

The lipophilicity of the nitrophenols, expressed as a water−solvent partition coefficient, P, has been investigated using the solvation equation, log P = c + eE + sS + aA + bB + vV. It is shown that this equation accounts quantitatively for lipophilicity in a selection of water−solvent systems, viz:  octanol, 1,2-dichloroethane, and cyclohexane. In the latter two systems, the major factor in the increased lipophilicity of 2-nitrophenol over 3- and 4-nitrophenol is the lack of hydrogen bond acidity of 2-nitrophenol. The water−octanol system differs in that the a coefficient is effectively zero, so that hydrogen bond acidity of solutes plays no part, and the three mononitrophenols then have similar lipophilicities. The dinitrophenols and picric acid are similarly discussed. The hydrogen bond acidity of 2,3-dinitrophenol (0.67) is very much larger than that of 2,4- or 2,5-dinitrophenol (0.09 and 0.11), indicating a very much reduced internal hydrogen bonding. A similar but much smaller effect occurs with 2,6-dinitrophenol (A = 0.17). Picric acid has a moderate hydrogen bond acidity (0.46) so that the phenolic OH is still available for external hydrogen bonding. These results are confirmed by ab initio calculations which show that 2,3- and 2,6-dinitrophenol and picric acid are significantly distorted away from planarity, which apparently disrupts their internal hydrogen bonding.

Lipophilicity of the nitrophenols

Solution phase, solid state, and theoretical investigations on the MacMillan imidazolidinone

QM/MM calculations were employed to investigate the role of hy- drogen bonding and p stacking in sev- eral single- and double-stranded cispla- tin-DNA structures. Computed geo- metrical parameters reproduce experi- mental structures of cisplatin and its complex with guanine-phosphate-gua- nine. Following QM/MM optimisation, single-point DFT calculations allowed estimation of intermolecular forces through atoms in molecules (AIM) analysis. Binding energies of platinated single-strand DNA qualitatively agree with myriad experimental and theoreti- cal studies showing that complexes of guanine are stronger than those of ade- nine. The topology of all studied com- plexes confirms that platination strong- ly affects the stability of both single- and double-stranded DNAs: Pt! N! H···X (X = N or O) interactions are ubiquitous in these complexes and ac- count for over 70% of all H-bonding interactions. The p stacking is greatly reduced by both mono- and bifunction- al complexation: the former causes a loss of about 3-4 kcalmol ! 1 , whereas the latter leads to more drastic disrup- tion. The effect of platination on Watson-Crick GC is similar to that found in previous studies: major redis- tribution of energy occurs, but the overall stability is barely affected. The BH&H/AMBER/AIM approach was also used to study platination of a double-stranded DNA octamer d(CCTG*G*TCC)·dA for which an experimental structure is available. Comparison between theory and experiment is satisfactory, and also reproduces previous DFT-based studies of analogous structures. The effect of platination is similar to that seen in model systems, although the effect on GC pairing was more pronounced. These calculations also reveal weaker, secondary interactions of the form Pt···O and Pt···N, detected in several single- and double-stranded DNA.

A QM/MM Study of Cisplatin–DNA Oligonucleotides: From Simple Models to Realistic Systems

The synthesis and characterisation of the monomeric amidinato-indium(I) and thallium(I) complexes, [M(Piso)]·PisoH, M = In or Tl, Piso−
				=
				[ArNC(But)NAr]−, Ar = C6H3Pri2-2,6, are reported. These complexes, in which the metal centre is chelated by the amidinate ligand in an N,η3-arene-fashion, can be considered as isomers of four-membered group 13 metal(I) carbene analogues. Theoretical studies have compared the relative energies of both isomeric forms of a model complex, [In{PhNC(H)NPh}].

Synthesis, characterisation and theoretical studies of amidinato-indium(I) and thallium(I) complexes: isomers of neutral group 13 metal(I) carbene analogues.

James Alexis Platts

Papers

Revisiting [PtCl2(cis-1,4-DACH)]: an underestimated antitumor drug with potential application to the treatment of oxaliplatin-refractory colorectal cancer

Lipophilicity of the nitrophenols

Solution phase, solid state, and theoretical investigations on the MacMillan imidazolidinone

A QM/MM Study of Cisplatin–DNA Oligonucleotides: From Simple Models to Realistic Systems

Synthesis, characterisation and theoretical studies of amidinato-indium(I) and thallium(I) complexes: isomers of neutral group 13 metal(I) carbene analogues.