Contributions of Various Noncovalent Bonds to the Interaction between an Amide and S‐Containing Molecules

Adhikari, Upendra; Scheiner, Steve

doi:10.1002/cphc.201200412

Cited by 15 publications

(8 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…42 A comparable interaction has been observed in crystal structures of a wide variety of substituted proline residues, including an especially strong one in an S -oxide for N -acetyl-4-thiaproline methyl ester ( 7 ). 22,79 Indeed, many functional groups can interact with carbonyl groups in an n →π* manner, including halide ions, 15 thiols/thioethers/disulfides, 80 and a variety of nitrogen heterocycles. 81,82 Similar types of electronic interactions involving carbonyl groups have been studied computationally and include complexes of SO 2 with carbon dioxide or formaldehyde.…”

Section: Contributions To Small Moleculesmentioning

confidence: 99%

The n→π* Interaction

2017

View full text Add to dashboard Cite

ConspectusThe carbonyl group holds a prominent position in chemistry and biology not only because it allows diverse transformations but also because it supports key intermolecular interactions, including hydrogen bonding. More recently, carbonyl groups have been found to interact with a variety of nucleophiles, including other carbonyl groups, in what we have termed an n→π* interaction. In an n→π* interaction, a nucleophile donates lone-pair (n) electron density into the empty π* orbital of a nearby carbonyl group. Mixing of these orbitals releases energy, resulting in an attractive interaction. Hints of such interactions were evident in small-molecule crystal structures as early as the 1970s, but not until 2001 was the role of such interactions articulated clearly.These non-covalent interactions were first discovered during investigations into the thermostability of the proline-rich protein collagen, which achieves a robust structure despite a relatively low potential for hydrogen bonding. It was found that by modulating the distance between two carbonyl groups in the peptide backbone, one could alter the conformational preferences of a peptide bond to proline. Specifically, only the trans conformation of a peptide bond to proline allows for an attractive interaction with an adjacent carbonyl group, so when one increases the proximity of the two carbonyl groups, one enhances their interaction and promotes the trans conformation of the peptide bond, which increases the thermostability of collagen.More recently, attention has been paid to the nature of these interactions. Some have argued that rather than resulting from electron donation, carbonyl interactions are a particular example of dipolar interactions that are well-approximated by classical mechanics. However, experimental evidence has demonstrated otherwise. Numerous examples now exist where an increase in the dipole moment of a carbonyl group decreases the strength of its interactions with other carbonyl groups, demonstrating unequivocally that a dipolar mechanism is insufficient to describe these interactions. Rather, these interactions have important quantum-mechanical character that can be evaluated through careful experimental analysis and judicious use of computation.Although individual n→π* interactions are relatively weak (∼0.3–0.7 kcal/mol), the ubiquity of carbonyl groups across chemistry and biology gives the n→π* interaction broad impact. In particular, the n→π* interaction is likely to play an important role in dictating protein structure. Indeed, bioinformatics analysis suggests that approximately one-third of residues in folded proteins satisfy the geometric requirements to engage in an n→π* interaction, which is likely to be of particular importance for the α-helix. Other carbonyl-dense polymeric materials like polyesters and peptoids are also influenced by n→π* interactions, as are a variety of small molecules, some with particular medicinal importance. Research will continue to identify molecules whose conformation and activity are affect...

show abstract

Section: Contributions To Small Moleculesmentioning

confidence: 99%

The n→π* Interaction

2017

View full text Add to dashboard Cite

show abstract

“…Apart from the intermolecular H-bond, the intramolecular sulfur H-bonds have also attracted considerable attention. − In biological systems, the structure as well as the nature of proteins are often determined by intramolecular sulfur H-bonds. Despite the ubiquity of intramolecular sulfur H-bonds, explorations of their photophysical properties, which help in understanding the fundamentals of protein folding, conformation, and function, remain rather scarce. − …”

Section: Introductionmentioning

confidence: 99%

Sulfur-Based Intramolecular Hydrogen-Bond: Excited-State Hydrogen-Bond On/Off Switch with Dual Room-Temperature Phosphorescence

Liu

Huang

et al. 2019

J. Am. Chem. Soc.

View full text Add to dashboard Cite

We report O−H----S hydrogen-bond (Hbond) formation and its excited-state intramolecular H-bond on/off reaction unveiled by room-temperature phosphorescence (RTP). In this seminal work, this phenomenon is demonstrated with 7-hydroxy-2,2-dimethyl-2,3-dihydro-1Hindene-1-thione (DM-7HIT), which possesses a strong polar (hydroxy)-dispersive (thione) type H-bond. Upon excitation, DM-7HIT exhibits anomalous dual RTP with maxima at 550 and 685 nm. This study found that the lowest lying excited state (S 1 ) of DM-7HIT is a sulfur nonbonding (n) to π* transition, which undergoes O−H bond flipping from S 1 (nπ*) to the non-H-bonded S′ 1 (nπ*) state, followed by intersystem crossing and internal conversion to populate the T′ 1 (nπ*) state. Fast H-bond on/off switching then takes place between T′ 1 (nπ*) and T 1 (nπ*), forming a pre-equilibrium that affords both the T′ 1 (nπ*, 685 nm) and T 1 (nπ*, 550 nm) RTP. The generality of the sulfur H-bond on/off switching mechanism, dubbed a molecule wiper, was rigorously evaluated with a variety of other H-bonded thiones, and these results open a new chapter in the chemistry of hydrogen bonds.

show abstract

“…Noncovalent interactions involving sulfur (S) atoms are prevalent in chemical 1,2 and biological systems, [3][4][5] and play an important role in molecular recognition 6 and protein stabilization. [7][8][9][10] Among these interactions, a divalent sulfur, which acts as an electron acceptor, can weakly coordinate to a proximate heteroatom oxygen (O) [11][12][13][14][15][16][17] and the aromatic ring or the unsaturated C-C bond (p).…”

Section: Introductionmentioning

confidence: 99%