Here we applied a novel method1a to predict pKa values of the guanidine functional group, which is a notoriously difficult. This method, which was developed in our lab, uses only one ab initio bond length obtained at a low level of theory. The method is shown to work for drug molecules, delivers prediction errors of less than 0.5 log units, successfully treats tautomerisation in close relation with experiment, and demonstrates strong correlations with only a few data points. The high structural content of the ab initio bond length makes a given data set essentially divide itself into high correlation subsets. One then observes that molecules within a subset possess a common substructure. Each high correlation subset exists in its own region of chemical space. The high correlation subset method is explored with respect to this position in chemical space, in particular tautomerisation. The proposed method is able to distinguish between different tautomeric forms and the preferred tautomeric form emerges naturally, in agreement with experiment.

Linear correlations were established between the calculated bond lengths and the pK a or σ I values for a series of 4-substituted bicyclo[2.2.2]octane-1-carboxylic acid and 4-cubane-1-carboxylic acid derivatives. The bond lengths have been calculated at a modest computational level, HF/6-31G(d), both in the gas phase and with the continuum solvation model, polarisable continuum model (PCM). In general, the best correlations are obtained when the PCM model is taken into account, especially when neutral and charged molecules are considered together. The best models in each case show square correlation coefficients (R 2 ) larger than 0.9 and indicate that they can be used as predictive tools. These results expand previous results that indicate the possibility of a relationship between gas phase bond length and pK a values in aqueous solution and indicate that such relationships are more general than hitherto expected.

Five-membered rings are found in a myriad of molecules important in a wide range of areas such as catalysis, nutrition, and drug and agrochemical design. Systematic insight into their largely unexplored chemical space benefits from first principle calculations presented here. This study comprehensively investigates a grand total of 764 different rings, all geometry optimized at the B3LYP/6-311+G(2d,p) level, from the perspective of Quantum Chemical Topology (QCT). For the first time, a 3D space of local topological properties was introduced, in order to characterize rings compactly. This space is called RCP space, after the so-called ring critical point. This space is analogous to BCP space, named after the bond critical point, which compactly and successfully characterizes a chemical bond. The relative positions of the rings in RCP space are determined by the nature of the ring scaffold, such as the heteroatoms within the ring or the number of π-bonds. The summed atomic QCT charges of the five ring atoms revealed five features (number and type of heteroatom, number of π-bonds, substituent and substitution site) that dictate a ring's net charge. Each feature independently contributes toward a ring's net charge. Each substituent has its own distinct and systematic effect on the ring's net charge, irrespective of the ring scaffold. Therefore, this work proves the possibility of designing a ring with specific properties by fine-tuning it through manipulation of these five features.

Near-infrared (near-IR) excitation produces little background signal from biological molecules, making near-IR fluorescence technology highly useful in proteomic and genomic applications. To increase the emissions of near-IR fluorophores, we examined the use of metal-enhanced fluorescence on these longer wavelength dyes. IRDye ® 700-and IRDye ® 800-labeled DNA oligonucleotides and proteins were spotted onto silver island film (SIF)-coated glass slides, and analyzed using a LI-COR Odyssey ® IR imaging system. We observed more than 18-fold enhancement of the IRDye ® 700 and 15-fold enhancement of the IRDye ® 800-labeled DNA oligonucleotides when spotted on SIF-coated surfaces compared with uncoated surfaces. We also demonstrated that the enhanced emissions produced on the SIFcoated slides remained linear over several orders of magnitude, that the emissions remained reproducible across a slide surface, and that the SIF-coated slide remained effective at enhancing emissions after 9 months of storage.Our results indicate that SIF-coated glass slides are effective at enhancing near-IR fluorescence and could be developed into an effective tool to aid in molecular biological applications.