Molecular calculations with the nonempirical ab initioMODPOT,VRDDO, and MODPOT/VRDDO procedures. XII. Carcinogenic 3-methylcholanthrene and its metabolites using a MERGE technique

Ab initio MODPOT/VRDDO/MERGE calculations were carried out on carcinogenic 3-methylcholanthrene (3-MCA) and its metabolites. The results for 3-MCA were compared to our earlier similar calculations for carcinogenic benzo(a)pyrene (BP). Both compounds 3-MCA and BP are carcinogenic and are metabolically activated by similar mechanisms but in different positions. Both the calculated wave functions for 3-MCA and BP and the electrostatic molecular potential contour maps generated from these wave functions correctly reflect the similarity of mechanisms of metabolic activation and the differences in position. Our calculated results both for BP and for 3-MCA reflect accurately their experimentally observed behavior. Thus this combination of theoretical techniques can be used with confidence to describe the behavior of the polycyclic aromatic hydrocarbons (PAH's) and their metabolites. The ab initio MODPOT/VRDDO method incorporates two very desirable options into our fast ab initio Gaussian programs: MODPOT –ab initio effective core model potentials—and a charge-conserving integral prescreening approximation which we named VRDDO (variable retention of diatomic differential overlap). For orbital energies and population analysis the MODPOT/VRDDO results agree to essentially three decimal places with completely ab initio calculations using the same valence atomic basis set. For this series of very closely related congeners our recent MERGE technique which allows reuse of integrals from a common skeletal fragment was used. The ab initio MODPOT/VRDDO/MERGE calculations were carried out for 3-MCA, 3-MCA oxides, 3-MCA dihydrodiols, and 3-MCA dihydrodiolepoxides. The metabolites investigated were 3-MCA 9,10-oxide; 3-MCA 7,8-oxide; 3-MCA 9,10-dihydrodiol [trans(axial, axial); trans(equatorial, equatorial); cis(axial, equatorial); cis(equatorial, axial)]; and 3-MCA 9,10-dihydrodiol–7,8-epoxide [for both conformations A and B of the dihydrodiol and for all stereoisomers of the dihydrodiolepoxides relative to below and above the plane: ααα, and ααβ αβα αββ βαα βαβ ββα and βββ (most stable)]. Calculations were also carried out for opening of the C₇? O? C₈ epoxide ring both towards C₇ and C₈ for the most stable isomer Aβββ (above the ring). Opening the epoxide ring between C₇ and O leads to a more stable intermediate than opening the epoxide ring between C₈ and O. Again, however, as with opening the epoxide ring in BP 7,8-dihydrodiol–9,10-epoxide there is no buildup of positive charge on C₇ in the 3-MCA metabolites as postulated by some cancer researchers, but rather the C₇ becomes slightly more negative. Nor is there a buildup of negative charge on the O atom, but rather it becomes slightly more positive. As the epoxide ring is opened further than 90° for the O? C₇? C₈ or O? C₈? C₇ angles, there appears to be a possible mixing of configurations that is being investigated further.     

Electrostatic molecular potential contour maps generated from ab initioMODPOT/VRDDO/MERGE wave functions of carcinogenic 3-methylcholanthrene and its metabolites

The electrostatic molecular potential contour maps were calculated for carcinogenic 3-methylcholanthrene (3-MCA) and a number of its metabolites {3-MCA 7,8-oxide and 3-MCA 9,10-oxide; 3-MCA 7,8-dihydrodiols[several stereoisomers: A trans(equatorial, equatorial) and A cis(equatorial, axial)]; 3-MCA 9,10-dihydrodiol–7,8-epoxide A βββ and 3-MCA 9,10-dihydrodiol–7,8-epoxide A αβα}. The maps were generated from our ab initio MODPOT/VRDDO/MERGE wave functions calculated for these species. The results of these maps for 3-MCA [similarly to our results for the maps we generated for benzo(a)pyrene (BP)] show that these electrostatic molecular potential contour maps can be used to indicate favored positions of attack for electrophilic species, such as “electrophilic” oxygen to form an epoxide as well as for positive ion attack. The 3-MCA maps indicate the favored site for attack and the pathways. The maps around 3-MCA 9,10-oxide and around 3-MCA 9,10-dihydrodiol-7,8-epoxide indicate the directional preferences for proton assisted epoxide ring opening. The maps around the 3-MCA dihydrodiols indicate that while for certain stereoisomers the “electrophilic” oxygen will prefer to attack from below, for other isomers it will prefer to attack from above. This gives great insight into the stereochemical preference for formation of different 3-MCA 9,10-dihydrodiol–7,8-epoxides.     

Molecular calculations with the MODPOT,VRDDO, and MODPOT/VRDDO procedures. IV. Boron hydrides and carboranes

Reference completely ab initio 6–3G and nonempirical 3G/MODPOT (ab initio effective core model potential) LCAO -MO -SCF calculations (using the same valence atomic orbital basis) were performed for a series of boron hydrides (B₄H₁₀, B₅H₉, B₅H₁₁, and B₆H₁₀) and a test 3G/MODPOT + VRDDO (variable retention of diatomic differential overlap for charge conserving integral prescreening) calculation were also performed for B₅H₉, B₆H₁₀, and B₁₀H₁₄. The agreement between the ab initio 6–3G and the corresponding 3G/MODPOT calculations was excellent for valence orbital energies, gross atomic populations, and dipole moments. The results also compared favorably to previous ab initio minimum STO basis results of Lipscomb and coworkers. The 3G/MODPOT + VRDDO calculations verified that for such spatially compact molecules (such as boron hydrides, which are fragments of polyhedra), the VRDDO procedure does not result in a noticeable savings in computer time for molecules of the size and shape of B₅H₉ and B₆H₁₀, in contrast to the savings previously realized for organic molecules of comparable atomic size. However, the agreement in calculational results between the 3G/MODPOT and the 3G/MODPOT +VRDDO results was still as extremely close as it had been for the organic molecules. 3G/MODPOT calculations were also carried out for B₈H₁₂, B₉H₁₅, B₁₀H₁₄, B₁₀H₁₄^?2, 1,2-C₂B₄H₆, and 1,6-C₂B₄H₆ and the results compared to the previous minimum STO basis results. For B₁₀H₁₄, the 3G/MODPOT +VRDDO method led to savings in computer time of 28% over the 3G/MODPOT method itself. The agreement of the 3G/MODPOT results with available experimental photoelectron spectral data for B₅H₉ and 1,6-C₂B₄H₆ was as good as that of the previous ab initio minimum STO basis calculations.     

Molecular calculations with the nonempirical ab initioMODPOT,VRDDO, and MODPOT/VRDDO procedures. XI. Theoretical study of the [C6H5OH ⃛OC6H5]− molecular complex: Ab initioMODPOT/VRDDO calculations and electrostatic molecular potential contour maps

The transport of C₆H₅O^? (or similarly charged moieties) through a lipoidal membrane may possibly be facilitated by forming complexes with the neutral compound. Thus, theoretical studies were performed on the model [C₆H₅OH ?OC₆H₅]^? molecular complex to obtain some information concerning the possible molecular and electronic structure of such complexes. Ab initio MODPOT /VRDDO SCF calculations were carried out on the neutral-anion dimer [C₆H₅OH ?OC₆H₅] to optimize the equilibrium geometry. Electrostatic molecular potential contour maps have been generated from the ab initio MODPOT /VRDDO results in the molecular plane and in the plane perpendicular to the molecular plane and intersecting the hydrogen bond O ?H? O. Difference maps have also been generated showing the change of potential on complex formation. There is a decrease of electrostatic interactions of the phenoxide anion upon complex formation with the neutral phenol. Counterpoise corrections for basis set size could not be made since calculation of the phenoxide anions in the basis set of the phenol plus the phenoxide anion led to an excited state for the phenoxide anion. This behavior is somewhat similar to that occurring in the stabilization method for excited states of negative ions as the size of the basis set is increased.     

Ab initioMODPOT/VRDDO/MERGE calculations on energetic compounds. IV. Nitrocubanes: Mononitro to octanitro quantum chemical calculations and electrostatic molecular potential contour maps

Ab initio MODPOT /VRDDO /MERGE calculations have been carried out for all the different position isomers of nitrocubane from mononitrocubane through octanitrocubane for a perfect symmetrical cubic cubane skeleton and for mononitrocubane through septanitrocubane for the almost cubic experimentally determined cubane skeleton. These calculations were carried out with our own rapid efficient ab initio programs which also incorporate a number of desirable computational strategies for calculations on large molecules. The skeletal total overlap population of the cubane skeleton (a theoretical index we showed years ago to be sensitive and predictive of stability of energetic molecular frameworks) indicates that successive nitration seems to increase the stability of the cubane skeleton. Successive nitration also seems to increase the total overlap population of the C? NO₂ bond. There are subtle differences depending on the exact positional isomer for a constant number of nitro groups—but the overall trend is definite. We have also generated electrostatic molecular potential contour (EMPC ) maps around these nitrocubanes. These maps are indicative of preferred positions of electrophilic and nucleophilic attack as a function of the number of nitro groups or their positions. These EMPC maps can also indicate, to a first approximation, a limit on how close these molecules may be able to approach each other in a crystal.     

Quantum chemical and physicochemical influences on structure–activity relations and drug design

Quantum chemical results will be presented on drugs, carcinogens, teratogens, and endogenous biomolecules using our new nonempirical ab initio MODPOT /VRDDO method, which incorporates as options to our ab initio LCAO -MO -SCF /CI programs ab initio effective core model potentials (MODPOT ) permitting one to calculate only the valence electrons explicitly yet accurately and an integral prescreening technique (VRDDO , variable retention of diatomic differential overlap) especially effective for spatially extended molecules. For molecules of the size of those of interest the MODPOT /VRDDO calculations run an order-of-magnitude faster than with our own fast ab initio programs and still retain accuracy to the third decimal place for the valence electron properties. We have also just implemented a new efficient MERGE technique which allows us to reuse integrals from a common skeletal fragment and only to have to recalculate those for a new atom or group or a change in its position. Examples will be presented of the use of this technique on a carcinogenic polycyclic aromatic hydrocarbon and its metabolites. The pK_a's, oil-water partition, and drug distribution coefficients as a sensitive function of pH have been measured for a number of drugs as well as for relevant endogenous biomolecules. The pH dependence of the lipophilicities of such molecules has profound implication on appropriate use of such data in QSAR studies.     

Ab initioMODPOT/VRDDO/MERGE calculations on energetic compounds. III. Nitroexplosives: Polyaminopolynitrobenzenes (including DATB,TATB, and tetryl)

Quantum chemical ab initio MODPOT /VRDDO calculations have been carried out on the following aminonitrobenzenes for which crystal structures had been determined experimentally: 4-nitroaniline; N,N-dimethyl-p-nitroaniline; 2,4,6-trinitroaniline; 1,3-diamino-2,4,6-trinitrobenzene (DATB—Form I); 1,3,5-triamino-2,4,6-trinitrobenzene (TATB); 2,3,4,6-tetranitroaniline; N-methyl-N,2,4,6-tetranitroaniline (Tetryl); and N-(β,β,β-trifluoroethyl)-N,2,4,6-tetranitroaniline. These quantum chemical calculations were performed on the molecules in their conformations as found in their crystal structures. The calculations were carried out with our own ab initio programs which also incorporate as options several desirable features for calculations on large molecules: ab initio effective core model potentials (MODPOT) which enable calculations of valence electrons only explicitly, yet accurately, and a charge conserving integral prescreening evaluation (which we named VRDDO-variable retention of diatomic differential overlap) especially effective for spatially extended molecules. Aminonitrobenzenes are especially interesting since there are inherent intramolecular ring distortions and deviations from planarity and intramolecular hydrogen bonds as well as intermolecular hydrogen bonds causing further deviations from planarity. The theoretical indices resulting from the quantum chemical calculations are relevant to a number of properties and behavioral characteristics of these molecules, both intramolecular and intermolecular. The charges on the atoms [from the gross atomic populations (GAP 's)] are needed for calculation of the atomic multipole–atomic multipole electrostatic contributions (a dominant factor) to the intermolecular interaction energies. These electrostatic interaction energies are part of the input necessary for calculations on the crystal packing and densities of these molecules. These GAP 's are also of value in interpreting the experimental photoelectron and ESCA spectra of these molecules. The total overlap populations (TOP 's) between atoms are related to the inherent bond strengths and can serve as a quantitative replacement for the old empirical bond length-bond order-bond energy relationship still used by explosives chemists to identify the “target bonds” (the weakest bonds). The TOP 's are of considerable value in predicting and tracing initiation and subsequent steps of explosive phenomena. The molecular orbital energies of the lowest unoccupied orbitals are of interest since nitroexplosives have been implicated in testicular toxicity and the initial metabolic activation appears to proceed through a one-electron reduction of the nitroexplosive.     

Ab-initio and approximately rigorous calculations on small,medium, and large systems

We have explored two areas of approximately rigorous calculations for computing nonempirical wave functions for heavy and/or large molecules orders of magnitude faster than with conventional ab-initio methods but with the same chemical accuracy. First, we have developed and used a series of programs (starting from our new fast sets of ab-initio Gaussian SCF and SCF -CI programs) incorporating ab-initio effective core model potentials (MOD -POT ) which allow one to treat only the valence electrons explicitly, plus a charge conserving integral prescreening, which cuts down significantly on the number of integrals that have to be calculated, stored, or processed for a large molecule. We have named this latter procedure VRDDO (variable retention of diatomic differential overlap). With these MODPOT and MODPOT /VRDDO methods we have explored a variety of small, medium, and large systems ranging from electron affinities of atoms through to molecules of biological interest and large boron hydrides. The results compared to ab-initio SCF or SCF /CI calcuations are very good, usually within 0.001 to 0.002 a.u. for orbital energies and gross atomic populations (GAPS ) and even better along potential energy curves. Secondly, we have explored the use of the MS -Xα method for less conventional molecules and properties than those for which it is customarily employed.     

17‐Oxo‐5α‐androstane‐3α,4β‐diyl diacetate and 17‐oxo‐5β‐androstane‐3α,4β‐diyl diacetate

The title compounds, both C₂₃H₃₄O₅, are the 5α and 5β configurations of two diacetate epimers. The 5β‐diacetate crystallizes in an hexagonal structure, unusual for steroid molecules. The unit cell has an accessible solvent volume of 358 ų, responsible for clathrate behaviour. The 5β‐epimer also features some shorter than average bond lengths in the 3α,4β‐acetoxy groups. The conformations of the molecules of both epimers are compared with those obtained through abinitio quantum chemistry calculations. Cohesion of the crystals can be attributed to van der Waals and weak molecular C—H⋯O interactions.     

Lateral thermal expansion of cellulose Iβ and IIII polymorphs

Measurements of the thermal expansion coefficients (TECs) of cellulose crystals in the lateral direction are reported. Oriented films of highly crystalline cellulose I_β and III_I were prepared and then investigated with X‐ray diffraction at specific temperatures from room temperature to 250 °C during the heating process. Cellulose I_β underwent a transition into the high‐temperature phase with the temperature increasing above 220–230 °C; cellulose III_I was transformed into cellulose I_β when the sample was heated above 200 °C. Therefore, the TECs of I_β and III_I below 200 °C were measured. For cellulose I_β, the TEC of the a axis increased linearly from room temperature at α_a = 4.3 × 10^?5 °C^?1 to 200 °C at α_a = 17.0 × 10^?5 °C^?1, but the TEC of the b axis was constant at α_b = 0.5 × 10^?5 °C^?1. Like cellulose I_β, cellulose III_I also showed an anisotropic thermal expansion in the lateral direction. The TECs of the a and b axes were α_a = 7.6 × 10^?5 °C^?1 and α_b = 0.8 × 10^?5 °C^?1. The anisotropic thermal expansion behaviors in the lateral direction for I_β and III_I were closely related to the intermolecular hydrogen‐bonding systems. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 1095–1102, 2002     

Some reactive properties of chlorooxirane,a likely carcinogenic metabolite of vinyl chloride

We have carried out a computational study of the reactive properties of chlorooxirane, the metabolically produced epoxide of vinyl chloride that is believed to be a direct-acting carcinogenic form of this molecule. An ab initio SCF-MO procedure (GAUSSIAN 70) was used to compute the energy requirements for stretching the C? Cl and both C? O bonds (S_N 1 reactivity) and to determine the course of the epoxide's possible S_N 2 reactions with ammonia, taken as a model for nucleophilic sites on DNA. The epoxide was assumed to be protonated; both the oxygen- and chloro-protonated forms were considered. At each step along the various reaction pathways, the structure of the system was reoptimized. For the oxygen-protonated epoxide, the C₁? O bond has a significantly lower energy barrier to stretching than does the C₂? O. (The carbon bearing the chlorine is designated C₁.) However, both are very much higher than that of the C? Cl bond in the chloro-protonated form, confirming our earlier finding of the relative weakness of this bond. In the S_N 2 processes involving ammonia, intermediate complexes are formed with both carbons of the oxygen-protonated epoxide, the C₂-complex being the more stable. However, the most stable ammonia complex occurs at C₁ of the chloro-protonated epoxide. Our calculated results, both the energies and also the geometry changes, allow us to propose two possible mechanisms for the formation of the 7-N-(2-oxoethyl) derivative of guanine that has been observed to be the major in vivo DNA alkylation product of vinyl chloride and has been suggested as possibly being responsible for its carcinogenicity. One of these mechanisms is S_N 1 and starts with the chloro-protonated epoxide; the other is S_N 2 and involves the oxygen-protonated form.     

An unusual conformation of gabapentin (Gpn) in Pyr‐Gpn‐NH‐NH‐Pyr stabilized by weak interactions

The crystal structure of N‐[(1‐{2‐oxo‐2‐[2‐(pyrazin‐2‐ylcarbonyl)hydrazin‐1‐yl]ethyl}cyclohexyl)methyl]pyrazine‐2‐carboxamide monohydrate (Pyr‐Gpn‐NN‐NH‐Pyr·H₂O), C₁₉H₂₃N₇O₃·H₂O, reveals an unusual trans–gauche (tg⁻) conformation for the gabapentin (Gpn) residue around the C^γ—C^β (θ₁) and C^β—C^α (θ₂) bonds. The molecular conformation is stabilized by intramolecular N—H...N hydrogen bonds and weak C—H...O interactions. The packing of the molecules in the crystal lattice shows a network of strong N—H...O and O—H...O hydrogen bonds together with weak C—H...O and π–π inteactions.     

Hydrogen bonding and structure of Ba2Ru2Cl10O·10H2O

Dibarium μ‐oxido‐bis[pentachloridoruthenate(IV)] decahydrate, Ba₂Ru₂Cl₁₀O·10H₂O, has been prepared from ruthenium(III) chloride and barium chloride in hydrochloric acid. It crystallizes in the monoclinic system (space group C2/c). The structure consists of alternating layers of [Ru₂Cl₁₀O]⁴⁻ and [Ba(H₂O)₇]²⁺ complex ions along the a direction. The O atom bonded to ruthenium occupies the 4e site, with symmetry, while the other atoms occupy general 8f sites. The overall structure is held together by O—H...O hydrogen bonds and O—H...Cl dipole–dipole interactions.     

Pseudopolymorphs of chelidamic acid and its dimethyl ester

Different tautomeric and zwitterionic forms of chelidamic acid (4‐hydroxypyridine‐2,6‐dicarboxylic acid) are present in the crystal structures of chelidamic acid methanol monosolvate, C₇H₅NO₅·CH₄O, (Ia), dimethylammonium chelidamate (dimethylammonium 6‐carboxy‐4‐hydroxypyridine‐2‐carboxylate), C₂H₈N⁺·C₇H₄NO₅⁻, (Ib), and chelidamic acid dimethyl sulfoxide monosolvate, C₇H₅NO₅·C₂H₆OS, (Ic). While the zwitterionic pyridinium carboxylate in (Ia) can be explained from the pK_a values, a (partially) deprotonated hydroxy group in the presence of a neutral carboxy group, as observed in (Ib) and (Ic), is unexpected. In (Ib), there are two formula units in the asymmetric unit with the chelidamic acid entities connected by a symmetric O—H...O hydrogen bond. Also, crystals of chelidamic acid dimethyl ester (dimethyl 4‐hydroxypyridine‐2,6‐dicarboxylate) were obtained as a monohydrate, C₉H₉NO₅·H₂O, (IIa), and as a solvent‐free modification, in which both ester molecules adopt the hydroxypyridine form. In (IIa), the solvent water molecule stabilizes the synperiplanar conformation of both carbonyl O atoms with respect to the pyridine N atom by two O—H...O hydrogen bonds, whereas an antiperiplanar arrangement is observed in the water‐free structure. A database study and ab initio energy calculations help to compare the stabilities of the various ester conformations.     

Conformation of cationic N,N‐di­methyl­glycine in di­methyl­glycinium tri­fluoro­acetate

In the title compound, C₄H₁₀NO₂⁺·C₂F₃O₂^?, the main N—C—COOH skeleton of the protonated amino acid is nearly planar. The C=O/C—N and C=O/O—H bonds are syn and the two methyl groups are gauche to the methyl­ene H atoms. The conformation of the cation in the crystal is compared to that given by ab initio calculations (Hartree–Fock, self‐consistent field molecular‐orbital theory). The tri­fluoro­acetate anion has the typical staggered conformation with usual bond distances and angles. The cation and anion form dimers through a strong O—H?O hydrogen bond which are further interconnected in infinite zigzag chains running parallel to the a axis by N—H?O bonds. Weaker C—H?O interactions involving the methyl groups and the carboxy O atoms of the cation occur between the chains.     

Three closely related dibenzazepine carboxylic acids: hydrogen‐bonded aggregation in one,two and three dimensions

In the structure of (6R*,11R*)‐5‐acetyl‐11‐ethyl‐6,11‐dihydro‐5H‐dibenzo[b,e]azepine‐6‐carboxylic acid, C₁₉H₁₉NO₃, (I), the molecules are linked into sheets by a combination of O—H...O and C—H...O hydrogen bonds; in the structure of the monomethyl analogue (6RS,11SR)‐5‐acetyl‐11‐ethyl‐2‐methyl‐6,11‐dihydro‐5H‐dibenzo[b,e]azepine‐6‐carboxylic acid, C₂₀H₂₁NO₃, (II), the molecules are linked into simple C(7) chains by O—H...O hydrogen bonds; and in the structure of the dimethyl analogue (6RS,11SR)‐5‐acetyl‐11‐ethyl‐1,3‐dimethyl‐6,11‐dihydro‐5H‐dibenzo[b,e]azepine‐6‐carboxylic acid, C₂₁H₂₃NO₃, (III), a combination of O—H...O, C—H...O and C—H...π(arene) hydrogen bonds links the molecules into a three‐dimensional framework structure. None of these structures exhibits the R₂²(8) dimer motif characteristic of simple carboxylic acids.     

Pukalide,a furanocembranolide from the soft coral Sinularia abrupta

We have assigned structure 1a to pukalide, which is a constituent of an alcyonarian, on the basis of spectral data. Pukalide is diterpenoid with a cembrane skeleton, bearing butenolide, epoxide, isopropenyl, and an unprecedented α,α-disubstituted furan-β-carboxylate function.     

5β,6β‐Epoxy‐17‐oxoandrostan‐3β‐yl acetate and 5β,6β‐epoxy‐20‐oxopregnan‐3β‐yl acetate

In the title compounds, C₂₁H₃₀O₄, (I), and C₂₃H₃₄O₄, (II), respectively, which are valuable intermediates in the synthesis of important steroid derivatives, rings A and B are cis‐(5β,10β)‐fused. The two molecules have similar conformations of rings A, B and C. The presence of the 5β,6β‐epoxide group induces a significant twist of the steroid nucleus and a strong flattening of the B ring. The different C17 substituents result in different conformations for ring D. Cohesion of the molecular packing is achieved in both compounds only by weak intermolecular interactions. The geometries of the molecules in the crystalline environment are compared with those of the free molecules as given by ab initio Roothan Hartree–Fock calculations. We show in this work that quantum mechanical ab initio methods reproduce well the details of the conformation of these molecules, including a large twist of the steroid nucleus. The calculated twist values are comparable, but are larger than the observed values, indicating a possible small effect of the crystal packing on the twist angles.     

Conformational study of phosphothreonine in aqueous solution. H and 13C NMR results

The 270 MHz ¹H and 22.6 MHz ¹³C NMR spectra of DL -phosphothreonine in D₂O have been measured and analysed as a function of pD. The trans-trans conformation of the fragment H-α? C-α? C-β? O? P predominates at all pD values. The C-β—O gauche contribution is notably larger for pD values in the range 7≤pD<10 than for acidic or more basic solutions which is in accordance with earlier results for phosphoserine (PSer).     

Five pseudopolymorphs and a cocrystal of nitrofurantoin

The antibiotic nitrofurantoin {systematic name: (E)‐1‐[(5‐nitro‐2‐furyl)methylideneamino]imidazolidine‐2,4‐dione} is not only used for the treatment of urinary tract infections, but also illegally applied as an animal food additive. Since derivatives of 2,6‐diaminopyridine might serve as artificial receptors for its recognition, we crystallized one potential drug–receptor complex, nitrofurantoin–2,6‐diacetamidopyridine (1/1), C₈H₆N₄O₅·C₉H₁₁N₃O₂, (I·II). It is characterized by one N—H...N and two N—H...O hydrogen bonds and confirms a previous NMR study. During the crystallization screening, several new pseudopolymorphs of both components were obtained, namely a nitrofurantoin dimethyl sulfoxide monosolvate, C₈H₆N₄O₅·C₂H₆OS, (Ia), a nitrofurantoin dimethyl sulfoxide hemisolvate, C₈H₆N₄O₅·0.5C₂H₆OS, (Ib), two nitrofurantoin dimethylacetamide monosolvates, C₈H₆N₄O₅·C₄H₉NO, (Ic) and (Id), and a nitrofurantoin dimethylacetamide disolvate, C₈H₆N₄O₅·2C₄H₉NO, (Ie), as well as a 2,6‐diacetamidopyridine dimethylformamide monosolvate, C₉H₁₁N₃O₂·C₃H₇NO, (IIa). Of these, (Ia), (Ic) and (Id) were formed during cocrystallization attempts with 1‐(4‐fluorophenyl)biguanide hydrochloride. Obviously nitrofurantoin prefers the higher‐energy conformation in the crystal structures, which all exhibit N—H...O and C—H...O hydrogen‐bond interactions. The latter are especially important for the crystal packing. 2,6‐Diacetamidopyridine shows some conformational flexibility depending on the hydrogen‐bond pattern.