Determination of a complex crystal structure in the absence of single crystals: analysis of powder X-ray diffraction data, guided by solid-state NMR and periodic DFT calculations, reveals a new 2'-deoxyguanosine structural motif

Abstract

Derivatives of guanine exhibit diverse supramolecular chemistry, with a variety of distinct hydrogen-bonding motifs reported in the solid state, including ribbons and quartets, which resemble the G-quadruplex found in nucleic acids with sequences rich in guanine. Reflecting this diversity, the solid-state structural properties of 3',5'-bis-O-decanoyl-2'-deoxyguanosine, reported in this paper, reveal a hydrogen-bonded guanine ribbon motif that has not been observed previously for 2'-deoxyguanosine derivatives. In this case, structure determination was carried out directly from powder XRD data, representing one of the most challenging organic molecular structures (a 90-atom molecule) that has been solved to date by this technique. While specific challenges were encountered in the structure determination process, a successful outcome was achieved by augmenting the powder XRD analysis with information derived from solid-state NMR data and with dispersion-corrected periodic DFT calculations for structure optimization. The synergy of experimental and computational methodologies demonstrated in the present work is likely to be an essential feature of strategies to further expand the application of powder XRD as a technique for structure determination of organic molecular materials of even greater complexity in the future.

Fig. 1. Molecular structure of dG(C₁₀)₂ showing the atom numbering scheme. The green bracket indicates the Watson–Crick hydrogen-bonding groups. The non-hydrogen atoms of the guanine moiety are labelled 1 to 10 and the non-hydrogen atoms of the 2′-deoxyribose moiety are labelled 1′ to 6′ and 10′. Note that the atom labelled here as N10 was labelled N2 or NH₂ in previous publications ^– on dG(C₁₀)₂.

Fig. 2. (a) The “narrow” guanine ribbon and (b) the “wide” guanine ribbon. In each case, the N–H···N hydrogen bonds are highlighted and the graph sets ^, for the hydrogen-bonded rings are indicated.

Fig. 3. The experimental powder XRD pattern for polymorph I of dG(C₁₀)₂. The full powder XRD pattern is shown on the left; the expanded region from 2θ = 6° to 40° is shown on the right.

Fig. 4. Results from fitting the powder XRD pattern (with baseline subtracted) for polymorph I of dG(C₁₀)₂. (a and b) Results from profile fitting using the Le Bail technique. (c and d) Results from the initial Rietveld refinement discussed in the text. (e and f) Results from the final Rietveld refinement following structure optimization using periodic DFT calculations. The full powder XRD pattern is shown in (a), (c) and (e). The expanded region from 2θ = 6° to 40° is shown in (b), (d) and (f). Red + marks, experimental data; green line, calculated data; magenta line, difference plot; black tick marks, peak positions.

Fig. 5. Crystal structure of polymorph I of dG(C₁₀)₂ viewed along the b-axis (parallel to the direction of the hydrogen-bonded ribbons).

Fig. 6. Crystal structure of polymorph I of dG(C₁₀)₂ showing the hydrogen-bonded ribbon of the guanine moieties. In this view, the b-axis is vertical.

Fig. 7. Illustration of π···π interactions between guanine moieties in the crystal structure of polymorph I of dG(C₁₀)₂. The dashed lines represent distances of ca. 3.5 Å.

Fig. 8. Correlation plots for the calculated and experimental values of the (a) ¹H, (b) ¹³C and (c) ¹⁵N isotropic chemical shifts for polymorph I of dG(C₁₀)₂. In each case, the dashed line corresponds to δ _iso(expt) = δ _iso(calc).