Nitrogen force fields

Lopes PEM, Lamoureux G, MacKerell AD, Polarizable Empirical Force Field for Nitrogen-containing Heteroaromatic Compounds Based on the Classical Drude Oscillator. Accepted for publication on J Comput Chem... 

The OPLS parameters (charges and Lennard-Jones terms) were obtained primarily via Monte Carlo simulations with particular emphasis on reproducing the experimental densities and heats of vaporization of liquids. Those simulations were performed iteratively as part of the parametrization, so better agreement with experiment is obtained than in previous studies where the simulations were usually carried out after the parametrization. Once the OPLS parametrization was completed, further simulations were also performed in order to test the new set of parameters in the calculation of other thermodynamic and structural properties of the system, besides its density and its heat of vaporization. Parameters have now been generated, among others, for water, alkanes, alkenes, alcohols, amides, alkyl chlorides, amines, carboxylic esters and acids, various sulfur and nitrogen compounds, and nitriles. A protein force field has been established as well. 

The MM2 force field3 is probably the most extensively parameterized and intensively used force field to date. It reproduces a variety of molecular properties such as geometry, dipole moments, conformational energies, barriers to rotation and heats of formation. Of particular importance for calculations of amines is that MM2 treats lone pairs on sp3 nitrogens (and oxygens) as pseudo atoms with a special atom type and parameters. A closely related force field, MM2 7, was derived from MM2 by Osawa and Jaime. MM2 uses the same potential functions as MM2, but employs a different set of parameters in an attempt to better reproduce barriers to rotation about single C—C bonds. 

The MM3 force field4 was developed in order to correct for some of the basic limitations and flows in MM2 by providing a better description of the molecular potential surface in terms of the potential functions and the parameters. One major outcome of the improved force field is the omission of lone pairs on nitrogen and oxygen since the reason for their inclusion in MM2 was no longer pertinent. This allows for a realistic... 

As in the case of the MM2 force field, parameterization of MM3 for amines was based mainly on experimental data with occasional references to ab initio calculations, mainly to evaluate relative conformational energies and derive appropriate torsional parameters. As mentioned above, one notable difference between the two force fields is the removal of lp on sp3 nitrogens from MM3. This simplifies the treatment of vibrational spectra and allows for a realistic treatment of nitrogen inversion which could not be handled by MM2. As usual with MM3, parameterization was aimed at reproducing a variety of molecular properties such as structure, steric energy, dipole moments, moments of inertia, heat of formation and vibrational spectra. A complete list of MM3 parameters for amines is provided in Reference 6. 

Two additional systems in which hydrogen bonds are expected to play a dominant role, ammonia-water complex and 2-aminoethanol, were calculated ab initio and by the new MM3 force field. Two ammonia-water complexes were considered, one with an N... H—O bridge (32) and the other with an O... H—N bridge (33). As expected from the relative H-donor/H-acceptor properties of nitrogen and oxygen, 32 was calculated... 

In this section we provide a short comparison of conformational energies for a set of nitrogen-containing molecules as obtained by several commonly used molecular mechanics force fields and by experiment. The data, collected in Table 22, were mostly taken from Reference 60 but several were calculated for this work. 

Unlike the MM2 force field, there is no explicit treatment of the nitrogen (or oxygen) lone pair in MM3. This allows one to calculate planar amine structures, as a model to... 

An extensive study of the conformational behavior of perhydroazepine 66 was carried out by Espinosa and coworkers105. This pure force field based analysis, with no reference to experiment or other theoretical methods, was part of a series of studies on cycloheptane, cycloheptene and some of their oxygen, sulfur and nitrogen heterocyclic analogs. MM2... 

The tetrahydrodibenzo[6,/][l,4]diazocines (458) and the tetrahydrodibenzo[6,/]-[l,5]diazocines (459), which have two nitrogens in the heterocyclic ring, as well as their sulfur analogs (460) and (461) show conformational properties similar to those of the monoaza compound (456). Typical data are included in Table 3. The assignments of conformations and transition states for these dibenzo derivatives are supported by force-field calculations and by detailed dynamic NMR measurements <73JCS(Pl)205>. 

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