The Hydrogen Bond: a Hundred Years and Counting

J. Indian Inst. Sci. A Multidisciplinary Reviews Journal ISSN: 0970-4140 Coden-JIISAD

The Hydrogen Bond: A Hundred Years and Counting

Steve Scheiner* REVIEW REVIEW ARTICLE

Abstract | Since its original inception, a great deal has been learned about the nature, properties, and applications of the H-bond. This review summarizes some of the unexpected paths that inquiry into this phenomenon has taken researchers. The transfer of the bridging proton from one molecule to another can occur not only in the ground electronic state, but also in various excited states. Study of the latter process has devel- oped insights into the relationships between the nature of the state, the strength of the H-bond, and the height of the transfer barrier. The enormous broadening of the range of atoms that can act as both proton donor and acceptor has led to the concept of the CH O HB, whose ··· properties are of immense importance in biomolecular structure and function. The idea that the central bridging proton can be replaced by any of various electronegative atoms has fostered the rapidly growing exploration of related noncovalent bonds that include halogen, chalcogen, pnicogen, and tetrel bonds.

Keywords: Halogen bond, Chalcogen bond, Pnicogen bond, Tetrel bond, Excited-state proton transfer, CH O H-bond ···

1 Introduction charge on the proton. The latter can thus attract Over the course of its century of study following the partial negative charge of an approaching its earliest conceptual formulation1,2, the hydro- nucleophile D. Another important factor resides gen bond (HB) has surrendered many of the in the perturbation of the electronic structure mysteries of its source of stability and its myriad of the two species as they approach one another. occurrences. Indeed, one might be hard pressed These alterations are typically referred to as to think of chemical or biological systems which induction, amongst other labels. At least con- are completely free of the effects of HBs. Pro- ceptually, the perturbations can be categorized teins, carbohydrates, and nucleic acids alike owe as internal and external. That is, charge shifts much of their structure to this phenomenon. The within a given molecule can result in polariza- many catalytic functions of enzymes are heavily tion energy, while charge transfer refers to any dependent upon HBs between amino acid resi- electron density that crosses an imaginary bor- dues and substrates. In fact, water would not even der that separates the two entities. For example, exist as a liquid at room and biological tempera- it is common to speak of n σ* transfer by tures were it not for H-bonding. And of course, which some density is shifted from→ the nonbond- one would not be able to understand many chem- ing, i.e. lone pair, orbital of the nucleophile into ical and biological processes that take place in the σ*(A–H) antibonding orbital of the proton aqueous environment without a thorough treat- donor. This accumulation of density in an anti- ment of the HBs that occur in each such system. bonding orbital has been taken as the source of 1 Department The HB owes a large segment of its stability the weakening of the A–H covalent bond, and of Chemistry to simple Coulombic forces. The normal polar- the resulting red shift of its stretching frequency, and Biochemistry, Utah State University Logan, ity of a A–H bond, wherein A is an electronega- itself a hallmark of H-bonding. The latter density Utah 84322‑0300, USA. tive atom such as O or N, places a partial positive shifts, both internal and external, are sometimes *[email protected]

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referred to as “covalent” contributions, although this particular sobriquet can be rather vague. To all the preceding terms, a last attractive contribu- tion arises in connection with London dispersion, a factor which is common to all molecular interactions, HBs being no exception. Of course, if all components of the interaction were attrac- Figure 1: Structure of malonaldehyde (M) and tive, an AH B HB would collapse into a single the transition state (TS) for the transfer of the pro- molecule. Such··· a collapse is prevented by Pauli ton between O atoms. exchange forces, similar in nature to what are colloquially referred to as steric repulsion. While the earliest concept of a AH D HB 2 Excited-State Proton Transfer was predicated on only the very electronegative··· Perhaps the frst observation of a proton trans- O, N, and F atoms as A or D participants, the fer in an excited state dates to 1956 and refers to list of atoms that can serve in this capacity has the intramolecular HB within a methyl salicylate greatly expanded over the years. All the halogens molecule51. The frst documented case of excited have been shown3–7 capable, as have numerous state concerted double proton transfer occurred chalcogen8–17 and pnicogen atoms18–20. The list in the 7-azaindole dimer52. Dual fuorescence in has been extended to metal atoms as well21–28, 3-hydroxyfavone was explained on the basis of both as proton donors and acceptors. In terms of this process in 197953, and this process was placed nucleophilic proton acceptors, the original idea of in the context of a photoinduced proton transfer lone pairs has also been extended, now to include laser as the process required only 8 ps54. In addi- -systems of units such as alkenes or aromat- π tion to lasers, the excited-state proton transfer ics29–35. Even the σ-bonds of molecules such as H 2 process has implications for data storage device can serve36–40 this function. Yet another new con- and optical switching55–57, Raman flters and scin- cept is connected41 with the ability of a through- tillation counters58, triplet quenchers59,60 and pol- space α-interaction between two lone pairs on ymer photostabilizers61,62. different atoms to strengthen the H-bond with a The poster boy for examining intramolecu- CH donor. In fact, the defnition of the HB has lar proton transfer, partly due to its simplicity, expanded so much over the past few decades is the malonaldehyde molecule which contains that an IUPAC group has established a new set of an internal OH O HB within a conjugated ring guidelines42 that are quite general. structure, as pictured··· in Fig. 1. The bridging pro- Since there are already available scores of ton can transfer across to the other O atom which works on HBs, including a number of extensive results in a symmetrically equivalent system. The monographs43–50 that concentrate on the central transition state (TS) for this transfer is a sym- issues of this phenomenon, this review focuses metric confguration with the proton equidistant on some of the currently developing frontiers of between the two O atoms. An early study of this the concept. As proton transfers within HBs have transfer63 comprised both the ground state S received a good deal of attention, and much has o and the frst excited * triplet state, T . The been written about them, the frst topic consid- π π 1 excitation into this state→ required on the order of ered here is the extension of this idea to proton 95 kcal/mol, and had several effects. It reduced transfers within excited states of HBs. Although the acidity of the OH group, as well as the basic- of some importance in a number of areas, such ity of the other O, and weakened the internal HB. as laser development, far less is known about Another result of the excitation is the addition of this process in any of its excited states than its antibonding character to the C O bond, which ground-state analog. A second frontier discussed causes it to elongate. The bottom= line is a higher here is the ability of the C atom to participate as pT barrier in T than in S , 13.6 versus 3.6 kcal/ a HB proton donor. Despite the low electronega- 1 o mol. This concept was expanded64 to include tivity of C, that generally precludes the normal other excited states as well. The 3 *, 3n *, 1 *, –A–H polarization, there is growing evidence of ππ π ππ + and 1n * states all displayed a rise in pT barrier CH O HBs, and their importance in numerous π versus the ground state, and indeed, a number phenomena.··· Lastly, discussion turns to a rapidly showed barrierless pT. The height of the barrier evolving feld of close cousins of HBs, which in was inversely correlated with the strength of the an apparent paradox, do not involve a H atom at internal HB. all.

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only 2 kcal/mol. The situation is generally similar 1 3 in the ππ* and ππ*. The situation is reversed in the singlet and triplet nπ* states, where O is pre- 1 ferred to N by 1 kcal/mol in ππ* and by 14 in the triplet. Unlike the malonaldehyde analog, most of the excited states of glyoxalmonohydrazine favor a nonplanar geometry. The specifc distortion mode is different for each state, as is the force toward nonplanarity. Permitting full distortion has a profound infuence upon the energetics of pT, switching the relative stability of N and 0 in both excited singlets, as compared to the transfer in the planar case. The situation was modifed 72 by replacing the H on the N by a CH2 group . This perturbation leads to an interesting= situation wherein the keto tautomer does not represent a Figure 2: O and N tautomers related to asymmet- minimum in the ground electronic state, but the ric pT in glyoxalmonohydrazine. reverse is true for either the frst excited singlet or triplet, where it is only the keto minimum that is present. This system thus represents a pT that is Research has progressed on malonaldehyde forced by the excitation. and its related systems over the ensuing years The entire system was remade73 into a 65–67 and continues unabated . The excited-state symmetric system, wherein both O atoms of proton transfer process is apparently important malonaldehyde are replaced by NH groups, even in terms of the ground state. A very recent as displayed in Fig. 3. As in the unsubstituted 68 examination of the proton transfer implicated malonaldehyde, a correlation is noted in that the two lowest excited singlet states in the prop- the stronger the HB, the lower the barrier to erties of the ground-state transfer via conical proton transfer. Nonplanar distortions are intersections. Measurements and later calcula- different for each excited state, but because tions place the height of the ground-state proton the distortions have similar energetic conse- transfer barrier at 5 kcal/mol, while the transfer quences for the equilibrium- and transition- 1 in the ππ* state is barrierless, and a high barrier state structures, the pT barrier of the 1n * 1 68–70 π occurs in the nπ* state , similar to the results state is little affected by permitting such defor- 64 obtained years earlier . mations. As for malonaldehyde molecule, the A number of modifcations to the basic transfer barriers in either case obey the order malonaldehyde conjugated ring structure were 1 3 3 ππ* < SO < ππ* < ′nπ* < nπ*. The barriers are examined next in the context of glyoxalmono- uniformly higher for the internitrogen trans- hydrazine. Replacement of the OCCCO ring by fers than for the OH··O interaction in malonal- 71 OCCNN raised the possibility of different ener- dehyde, which is attributed to the longer HBs. gies for the enol and keto structures, i.e. proton For any given HB, the interoxygen transfer has on O or N, as indicated in Fig. 2. The ground- a slightly higher barrier than does NH–N by state pT potential contains two minima, O and N, 2–3 kcal/mol. with the latter lower by some 9 kcal/mol. The pT The effects of the fve-membered ring size from N to O must pass over an energy barrier of of malonaldehyde changes to both four and

Figure 3: Symmetric proton transfer in 1,5-Diaza-1,3-pentadiene.

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Figure 4: Four (4′) and six (6′) membered anionic ring analogues of malonaldehyde (5).

six, coupled with addition of a negative charge, of hydroxyacetophenone is removed. In most while holding the HB atoms to O, was exam- respects, the addition of the aromatic system ined74 in a series of systems pictured in Fig. 4. exerts little infuence upon the properties of 1 The pT barriers correlate strongly with various malonaldehyde. With the exception of the ππ* geometric and energetic markers of the strength state, electronic excitation weakens the HB and of the HB. The HB is weakened by n π* exci- simultaneously raises the pT barrier in either tation, particularly for the neutral →molecule, system. Unlike the symmetric transfer potential resulting in a higher barrier. In the case of the in malonaldehyde, the enol and keto tautomers 3 two anions, excitation to ππ* strengthens the of oHBA are chemically distinct. ππ* excitation HB, while the result is more ambiguous for the reverses the preference for the enol tautomer in 1 ππ* state. This trend is reversed in malonalde- the ground state. This reversal is connected with hyde where the singlet is strengthened by the the changing degree of aromaticity in the phenyl excitation and the triplet weakened. Some of ring of oHBA. The asymmetric transfer poten- these patterns were traced directly to the nature tial in oHBA leads to forward and reverse bar- of the pertinent orbitals and the density shifts riers of different magnitude. When this factor arising from the excitation. is accounted for by an averaging procedure, the The malonaldyde theme was added to a phe- transfer barriers in oHBA are similar to those of nyl ring in such a way as to perturb the intrinsic the corresponding states of malonaldehyde. symmetry of the pT process, which was aug- Another variation of the theme shrunk the mented by inclusion of a methyl group in o– HB segment down to a four-membered OCCO hydroxyacetophenone75, as illustrated in Fig. 5. ring, which is then attached to a seven-membered The correlated pT potentials for the ground and hydrocarbon ring as in tropolone, illustrated in 77 frst excited singlet states each contain a single Fig. 6. The pT process in the S1 state is charac- minimum, but they differ in placement of the terized by a low barrier, such that only one dou- proton. Hence the S0 S1 excitation yields a blet of the OH stretching frequency lies below spontaneous pT, from the→ hydroxyl O to the car- the peak of the pT barrier. A careful analysis of bonyl O. Attachment to a phenyl ring was also the tunneling splitting revealed that bending examined76 in the closely related o-hydroxyben- vibrations play only a minor role in the pT pro- zaldehyde (oHBA), wherein the methyl group cess so that a two-dimensional stretching model,

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Figure 5: Primary and tautomeric forms of o-hydroxyacetophenone.

particular how the pT potential is affected by F substitution78, as indicated in Fig. 7. Many of the effects are inductive; the electronegative F makes the proximate N or O atom a stronger acid or weaker base and thereby modulates the preferred position of the proton. The magnitude of the perturbation diminishes as the site of substitution is further removed from the HB. This principle also controls the manner in which F affects the geometry and strength of the intramolecular HB in both the enol and keto tautomers. Whereas these notions apply fairly consistently to the ground state and excited ππ* singlet and triplet, a num- 1 ber of anomalous patterns emerged in the nπ* Figure 6: Four-membered OCCO ring attached state. In general, the effects of fuorosubstitution to 7-membered ring in tropolone system. are smaller in magnitude than the changes that occur in the pT properties as a result of electronic excitation. involving only O O and O–H stretches ought to ··· While the results described above concerned be adequate. intramolecular pT through an internal HB, it is Attachment to a phenyl ring was also con- also of interest to consider intermolecular pro- sidered in the context of salicylaldimine, which cesses. An example is the transfer of a proton contains the symmetric OCCCN ring, and in from phenol to ammonia79 which would morph

Figure 7: Placement of a F-substituent into salicylaldimine in either X1 or X2 positions.

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the system from a neutral PhOH NH3 pair to CH of the aromatic ring was also a viable proton ··· 108 a PhO − +HNH3 ion pair. While such a trans- donor. fer is highly··· disfavored in the ground state, the It had been part of conventional wisdom that situation changes dramatically in the frst excited it is the NH··O HBs between strands that hold the singlet state where the pT potential develops a β-sheet together. But study of the atomic positions second minimum, with the two confgurations of a β-sheet in Fig. 8 shows that CH groups are roughly equal in energy. also in position to donate a proton to the peptide More details about these results, and the spe- O of the neighboring strand. Quantum calcula- cifc methods applied can be found in the original tions109 showed that these putative interstrand papers as well as a summarizing Feature Article80. CH··O HBs are competitive in strength with Work has certainly not ceased in this feld, which NH··O, and serve as an integral component in the continues apace81–83 from both computational stability of the β-sheet, a fnding that has since and experimental perspectives. been confrmed by others110–115. Despite a longstanding notion that the strength of a HB between two given groups depends only 3 CH O H-Bonds upon their relative geometry, i.e. HB length and ··· Another frontier in the defnition and proper- angles, calculations showed this to only be part ties of H-bonding lies on the weak end of the of the story. Even when a pair of peptide groups spectrum. The CH group is so pervasive in is locked into a given confguration116, the inter- chemistry and biochemistry, that its ability to action energy is highly sensitive to the overall participate in a HB is of utmost importance. structure of the polypeptide chain on which they While a simple alkane does not provide a suf- reside. In particular, extended conformations of a fciently polar CH group to act in this fashion, polypeptide are capable of only weak NH··O HBs, it is well documented that a HB is formed if and the interstrand NH O H-bonds in β-sheets ··· the C changes its hybridization84,85 from sp3 to are weaker than those found in other conforma- sp, as in HC CH or N CH. Another means tions, such as helices, ribbons, and β-bends, even if to amplify the≡ CH polarity≡ is the placement of the specifc HB geometries are similar. In a related electron-withdrawing substituents on the C, as vein, the CH··O HB is even stronger than NH··O would naturally occur in a protein where each within the context of a simple dipeptide106 when in α C H is fanked by a pair of peptide groups. As a C5 geometry, a small model somewhat similar to work proceeded on CH O HBs, it was soon the β-sheet. These trends are not restricted only to apparent that some of them··· have an unusual in vacuo settings, but retain their integrity within quirk. Instead of shifting the A–H stretch- the context of a dielectric continuum model of a ing frequency to the red as had been taken as protein interior117. a necessary condition of a AH··D HB, a cer- The importance of the CH··O HB is not tain subset of CH··O interactions shifted the limited to structural issues, but also plays a role C–H stretch to the blue86–92. While there were in various enzymatic mechanisms. These ideas some initial complaints that such a shift in the were tested within the context of the serine wrong direction ought to disqualify this inter- proteinase family of enzymes118. Earlier, work- action as being a true HB, it fulflled all other ers had suggested what they called a “ring-fip” typical criteria. This anomaly was soon deter- hypothesis involving a 180° rotation of a key mined to result from the fact that the direction His residue as a vital step in the catalysis. This of shift arises from a delicate balance between mechanism relied on the presence of a CH··O forces, some tending to shift to the red, and oth- HB to stabilize one of the intermediates in the ers to the blue93–101. While the former tend to formation of the tetrahedral intermediate. The win out in most HBs, the subtle balance simply calculations were generally supportive of this shifts in the opposite direction for some CH O idea but raised some important discrepancies HBs102–106. ··· that required resolution before its acceptance. Within the realm of proteins, the most com- This sort of HB has implications in other enzy- mon CH group capable to participate in such a matic mechanisms as well119. There are also bond is the C αH group which is surrounded by contributions of this weak HB as a determin- a pair of electron-withdrawing peptide groups. ing factor120–122 in the conformation of certain Calculations have demonstrated the strength of organic systems. Needless to say, even normally these bonds107 as just less than that of a standard weak HBs can be strengthened by the acquisi- NH··O interaction. With respect to sidechains tion of charge on either the proton donor or containing an aromatic group, e.g. Tyr or His, the acceptor group.123–125

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Figure 8: Pair of polypeptide strands in the antiparallel β-sheet arrangement, indicating putative HBs by broken lines. Brown atoms represent generic R groups of amino acids.

As experimentalists continue to examine electrostatic potential in this region, commonly systems for the presence of CH··O HBs, they referred to as a σ-hole132–136. It is this localized require certain trademark or fngerprint char- positive region which can attract a nucleophile, in acteristics for which to search. In addition to such the same way as does the H in a AH··D HB. geometric aspects which are already fairly well This idea of a halogen bond (XB) is not understood, it is common to apply spectro- restricted only to halogen atoms, but is com- scopic methods to these biological systems. mon also to chalcogen, pnicogen, and even tet- Quantum calculations have provided some such rel atoms, in their eponymously named bonds. characteristics for which to search126–128. It was There are certain fne point differences amongst noted earlier that CH stretching frequencies can these bonds. For example, while a univalent X shift in either direction; nonetheless, a blue shift atom displays a single σ-hole lying along the would be a valuable indicator as it would not extension of the R–X bond, a divalent Y chal- occur in the absence of such a bond. A down- cogen atom will typically contain two such feld shift of the bridging proton’s NMR signal σ-holes, each lying along an extension of the would reinforce this supposition. With respect two R–Y bonds. These holes will not be able to to the proton acceptor, a large upfeld shift of lie directly opposite the bond, since the high the O chemical shift, by as much as 16 ppm, can electron density of the two Y lone pairs will tend serve as another indicator. to push the holes away from them. This distinc- tion is illustrated in the comparison of FCl with HFS in Fig. 9a, b, respectively. In each case, the 4 Cousins of the H-Bond blue oval represents the σ* antibonding orbital, Another HB frontier that has been approached is FCl in a and FS in b, along which the reduced its defnition as an interaction involving a bridg- electron density would tend toward a σ-hole. ing proton. Suppose this H was to be replaced by The Cl atom of FCl contains three lone pairs, a different atom, but the various properties were represented by red ovals, whose density would to remain largely intact. Early work had suggested push the positive potential, i.e. the σ-hole, away such a phenomenon, wherein H could be replaced from themselves. Due to their symmetric dis- by any of several halogen (X) atoms129–131. The position, the blue region of the potential lies ability of the X to serve in this capacity rests on directly along the F–Cl axis and the σ* orbital the highly anisotropic charge distribution which direction. On the other hand, there are only surrounds it. While its electronegativity imparts two lone pairs on the S atom in Fig. 9b, which to it an overall negative partial charge, there is a together push the σ-hole down away from them. reduced density along the extension of the R–X A nucleophile would thus tend toward this blue region σ-hole, and a nonlinear FS Nuc align- bond, which has been termed a “polar fatten- ··· ing”, which in turn causes a region of positive ment. A similar nonlinear arrangement between

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Figure 9: Molecular electrostatic potential sur- rounding indicated molecules, with blue indicating positive and negative represented by red regions. Light blue oval designates the σ*(F–A) antibonding orbital that lies directly opposite the Figure 10: Variation of second-order energy E(2) F–A covalent bond. Lone pairs on each central A and amount of charge transferred from N lone atom are indicated by red ovals. pair of NH3 to σ*(XP) antibonding orbital of H2PX as a function of interaction energy ΔE.

the F–P bond extension and the σ-hole would In fact, this substitution is even capable of be expected for a pnicogen bond (ZB), in making frst-row N capable of accepting charge Fig. 9c, due to a single lone pair. The absence of in a N··N pnicogen bond141 despite the reluctance any lone pairs on the Si atom in Fig. 9d would of frst-row atoms to engage in such bonds. With allow the blue positive potential σ-hole to align respect to the electronegativity and polarizability perfectly with the σ*(F–Si) antibonding orbital, of the pnicogen atom, larger atoms yield stronger resulting in a linear Tetrel bond (TB). It must ZBs140,142–144 in the order P < As < Sb. This trend be noted that since the high electron density has no parallel to HBs as it is always the proton of lone pairs mitigate the positively charged that acts as bridge. σ-hole, the progressive decrease of lone pair As one might anticipate, since halogen and number in the sequence halogen > chalco- pnicogen atoms can replace the proton in HBs, gen > pnicogen > tetrel would tend to enhance the same idea can be extended to chalcogen (S, the σ-hole intensity in the same order. Se, etc.) atoms as well. Work by our group145–149 After an initial study that demonstrated that as well as numerous others150–156 elaborated on a P N interaction is energetically preferred to these ideas. Indeed, there is currently a IUPAC a PH··· N HB137, more detailed study138 showed group tasked with adopting a working defnition this to··· be a characteristic of pnicogen bonds in of a chalcogen bond, with others to follow later general. Part of the interaction arises from the for the other sorts. The extension to tetrel atoms donation of charge from the N lone pair into (the Si family) occurred soon thereafter, show- the σ*(PH) antibonding orbital. This transfer is ing many of the same controlling factors that are identical to that in a PH··B HB, except that it is present for X, Y, and Z atoms157–160. The normally the P-end of this orbital which points toward the tetravalent tetrel atoms introduced a new factor N, rather than the H-end. The strength of such which had been less prominent in the other sorts a ZB is heightened when the H is replaced by of bonds. In order for a base to approach the cen- an electron-withdrawing agent such as F139. Fig- tral tetrel atom along a face of the tetrahedron, ure 10 shows how the interaction energy ΔE rises the three proximate substituents must “peel back” as the substituent’s electron-withdrawing power away from this base, changing the originally tetra- increases from CH3 and H up to F and NO2 for hedral structure into something akin to a trigonal 140 the XH 2P NH3 series . Along with this rise in bipyramid. There is thus a good deal of deforma- binding is··· a concomitant amount of charge trans- tion energy that must be surmounted161–163 if this ferred from the base to the Lewis acid, as meas- tetrel bond is to form. This deformation energy ured either by NBO values of E(2) or the total makes the tetrel bond formation less exothermic charge on the entire subunit Δq. than it would otherwise be, and can even control the particular site at which the base can attack.

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The idea of tetrel bonds brought up an inter- interactions with a halide, furnishing both very esting issue. It had typically been considered that strong interactions, and a marked preference for a nucleophile lying along the R–C extension of F − over other halides. an R–CH3 group constituted a trifurcated HB, i.e. interaction with three H atoms. And, there are certainly many such geometrical disposi- 5 Perspective tions of this sort, in both chemical and biologi- It would seem then that even after a full cen- cal systems164. But how can one distinguish this tury of study, which has provided a wealth of idea of a trifurcated HB from the newer concept information and insights into the H-bond, we of a R–C D tetrel bond? Indeed, there are spec- are nowhere near the end of learning its secrets. ··· troscopic markers that are different for the two Its fundamental nature is a template for a much sorts of interactions165,166, and it is hoped that the broader set of interactions. Far from the initial future will witness attempts to distinguish these thoughts that the A and B atoms in the AH B two types of interactions. interaction are limited to O, N, and F, the set··· of As work has progressed in this area, it has participating atoms has broadened so widely over become recognized that the positive regions are the years, such that an atom that cannot serve not limited only to σ-holes lying along the exten- in this capacity would be the exception, not the sion of a particular covalent bond. There are rule. In particular, the entry of the CH group, π-holes as well, wherein the positive potential sits into the club of proton-donating members, has above the plane of a molecule, as in H 2SiO for opened wide new vistas concerning the struc- example, in the vicinity of the electronic π-cloud. ture and function of large molecules including This broadening of the idea has been probed proteins and nucleic acids, vistas that are only extensively and shown that while the π-hole inter- recently beginning to be explored. The possibility actions are usually weaker than their σ parallels, of proton transfer within a given HB has enor- this trend is sometimes reversed158,167–169, espe- mous implications as well, not only in the ground cially when the π-hole lies above a triel atom such electronic state but also in various excited states 170–173 as B or Al . Of course, such π-hole interac- which open new sets of practical applications. tions do not have a H-bonding parallel. And the further broadening of the original con- These relatives of the HB are hardly exotic cept of a proton-bridging HB to systems where academic novelties, but have a wide range of this central proton is replaced by any of a large applications, such as serving as synthons in self- number of electronegative atoms has introduced assembling networks174, biological catalysis175, an entire new area that encompasses halogen, oxidative addition176, self-assembled monolay- chalcogen, pnicogen, and tetrel bonds, again an 177 178 ers , S N2 reaction catalysis , design of func- area whose impact is only beginning to emerge. tional mesomorphic materials179, and even Given all that has transpired in the last cen- directed construction of supramolecular quad- tury, it would be foolish to presume that we have ruple and double helices180. One of the more reached the fnal border of what the H-bond has interesting uses concerns selective binding of ani- to teach us. One can only hope that the next cen- ons181–188. It was realized that the replacement of tury of inquiry will be as fruitful as the frst. the H atom of certain multidentate anion receptors with a halogen atom allowed them to engage Publisher’s Note in halogen bonds with an anion, which in turn Springer Nature remains neutral with regard to strengthened the interaction, and enhanced the jurisdictional claims in published maps and insti- selectivity for certain anions over others. tutional affliations. Calculations were applied to this idea, and were able to suggest certain options that ought Received: 28 September 2019 Accepted: 30 October to enhance these abilities. Optimal choices 2019 of particular halogen atoms were proposed, Published online:18 November 2019 along with identifcation of chemical groups to which they ought to be bonded, spacer groups between the halogen bonding groups, and overall charge189–191. Subsequent work broadened this References idea beyond simply halogen bonds, but consid- 1. Latimer WM, Rodebush WH (1920) Polarity and ered their chalcogen, pnicogen, and tetrel coun- ionization from the standpoint of the Lewis theory of terparts192–195. It was concluded that tetrel bonds valence. J Am Chem Soc 42:1419–1433 offered a particularly tempting choice for their

69 J. Indian Inst. Sci. | VOL 100:1 | 61–76 January 2020 | journal.iisc.ernet.in 1 3 S. Scheiner

2. Pauling L (1940) The nature of the chemical bond. Cor- 16. Biswal HS, Wategaonkar S (2011) OH X (X O, S) ··· = nell University Press, Ithaca, p 450 hydrogen bonding in thetrahydrofuran and tetrahy- 3. O’Reilly D, Stein RS, Patrascu MB, Jana SK, Kurian J, drothiophene. J Chem Phys 135:134306 Moitessier N, Damha MJ (2018) Exploring atypical fu- 17. Biswal HS, Wategaonkar S (2009) Sulfur, not too far orine-hydrogen bonds and their effects on nucleoside behind O, N, and C: SH hydrogen bond. J Phys ···π conformations. Chem Eur J 24:16432–16439 Chem A 113:12774–12782 4. Chaudhari SR, Mogurampelly S, Suryaprakash N 18. Møller KH, Hansen AS, Kjaergaard HG (2015) Gas … (2013) Engagement of CF 3 group in N-H F-C hydro- phase detection of the NH–P hydrogen bond and gen bond in the solution state: NMR spectroscopy and importance of secondary interactions. J Phys Chem A MD simulation studies. J Phys Chem B 117:1123–1129 119:10988–10998

5. Nadas J, Vukovic S, Hay BP (2012) Alkyl chlorides 19. Viana RB, da Silva ABF (2015) Interaction between PH3 as hydrogen bond acceptors. Comput Theor Chem and small water clusters: understanding the electronic 988:75–80 and spectroscopic properties. Comput Theor Chem 6. Lai LL, Yang CM, Liu CC, Cheng KL, Wen YS, Hung 1059:35–44 CH, Luo TT, Kuo MY (2011) Direct evidence of a 20. Hansen AS, Du L, Kjaergaard HG (2014) Positively liquid-crystalline phase induced by intermolecular charged phosphorus as a hydrogen bond acceptor. J CH …Cl interactions on the basis of IR spectroscopy Phys Chem Lett 5:4225–4231 and theoretical simulations. Chem Eur J 17:111–116 21. Schmidbaur H (2019) Proof of concept for hydro- 7. Brammer L, Bruton EA, Sherwood P (2001) Under- gen bonding to gold, Au H X. Angew Chem Int Ed ··· − standing the behavior of halogens as hydrogen bond 58:5806–5809 acceptors. Cryst Growth Des 1:277–290 22. Wang P, Xu H-G, Cao G-J, Zhang W-J, Xu X-L, Zheng 8. Mishra KK, Singh SK, Kumar S, Singh G, Sarkar B, W-J (2017) Nonconventional hydrogen bonds between Madhusudhan MS, Das A (2019) Water-mediated sele- silver anion and nucleobases: size-selected anion pho- nium hydrogen-bonding in proteins: PDB analysis and toelectron spectroscopy and density functional calcula- gas-phase spectroscopy of model complexes. J Phys tions. J Phys Chem A 121:8973–8981 Chem A 123:5995–6002 23. Sanchez-de-Armas R, Ahlquist MSG (2015) On the 9. Sahoo DK, Jena S, Dutta J, Rana A, Biswal HS (2019) nature of hydrogen bonds to platinum(II)—Which Nature and strength of M–H S and M–H Se interaction can predict their strength? Phys Chem ··· ··· (M Mn, Fe, & Co) hydrogen bond. J Phys Chem A Chem Phys 17:812–816 = 123:2227–2236 24. Schmidbaur H, Raubenheimer HG, Dobrzanska L 10. Das A, Mandal PK, Lovas FJ, Medcraft C, Walker NR, (2014) The gold-hydrogen bond, Au–H, and the

Arunan E (2018) The H2S dimer is hydrogen-bonded: hydrogen bond to gold, AuH–X. Chem Soc Rev direct confrmation from microwave spectroscopy. 43:345–380 Angew Chem Int Ed 57:15199–15203 25. Falvello LR (2010) The hydrogen bond, front and 11. Wategaonkar S, Bhattacherjee A (2018) N–H S inter- center. Angew Chem Int Ed Engl 49:10045–10047 ··· action continues to be an enigma: experimental and 26. Rizzato S, Bergès J, Mason SA, Albinati A, Kozelka J computational investigations of hydrogen-bonded (2010) Dispersion-driven hydrogen bonding: pre- complexes of benzimidazole with thioethers. J Phys dicted hydrogen bond between water and patinum(II) Chem A 122:4313–4321 identifed by neutron diffraction. Angew Chem Int Ed 12. Mundlapati VR, Gautam S, Sahoo DK, Ghosh A, Engl 49:7440–7443 Biswal HS (2017) Thioamide, a hydrogen bond accep- 27. Kryachko ES, Remacle F (2005) Three-gold clusters tor in proteins and nucleic acids. J Phys Chem Lett form nonconventional hydrogen bonds O–H…Au and 8:4573–4579 N–H…Au with formamide and formic acid. Chem 13. Mishra KK, Singh SK, Ghosh P, Ghosh D, Das A (2017) Phys Lett 404:142–149 The nature of selenium hydrogen bonding: gas phase 28. Kozelka J (2015) Agostic and hydrogen-bonding X–H · spectroscopy and quantum chemistry calculations. M interactions involving a d8 metal center: recent · · Phys Chem Chem Phys 19:24179–24187 advances towards their understanding. In: Scheiner S 14. Andersen CL, Jensen CS, Mackeprang K, Du L, Jør- (ed) Noncovalent forces, vol 19. Springer, Dordrecht, gensen S, Kjaergaard HG (2014) Similar strength of the pp 129–158 NH O and NH S hydrogen bonds in binary com- 29. Ventura E, Monte SAD, Fragoso W, Braga CF, Araújo ··· ··· plexes. J Phys Chem A 118:11074–11082 RCMU (2006) Effects of π bond type, backbone size, 15. Mintz BJ, Parks JM (2012) Benchmark interaction and halogen on structural and spectroscopic proper- … energies for bologically relevant noncovalent com- ties of hydrogen-bonded complexes of the XH π type plexes containing divalent sulfur. J Phys Chem A between alkenes or alkynes and haloacids (HF and 116:1086–1092 HCl). Int J Quantum Chem 106:1009–1019

70 1 3 J. Indian Inst. Sci.| VOL 100:1 | 61–76 January 2020 | journal.iisc.ernet.in The Hydrogen Bond

30. Karle IL, Butcher RJ, Wolak MA, Filho DADS, Uchida 45. Joesten MD, Schaad LJ (1974) Hydrogen bonding. Mar- M, Brédas JL, Kafaf ZH (2007) Cooperative CH cel Dekker, New York, p 622 ···π interactions in the crystal structure of 2,5-di(3- 46. Gilli G, Gilli P (2009) The nature of the hydrogen bond. biphenyl)-1,1-dimethyl-3,4-diphenyl-silole and Its Oxford University Press, Oxford, p 313 effect on Its electronic properties. J Phys Chem C 47. Schuster P (1984) Hydrogen bonds, vol 120. Springer, 111:9543–9547 Berlin, p 117 31. Nishio M, Umezawa Y, Honda K, Tsuboyama S, 48. Schuster P, Zundel G, Sandorfy C (1976) The hydrogen Suezawa H (2009) CH/π hydrogen bonds in organic bond. Recent developments in theory and experiments. and organometallic chemistry. CrystEngComm North-Holland Publishing Co., Amsterdam 11:1757–1788 49. Grabowski SJ (2006) Hydrogen bonding—new insights. 32. Gierszal KP, Davis JG, Hands MD, Wilcox DS, Slip- Springer, Dordrecht chenko LV, Ben-Amotz D (2011) π-Hydrogen bond- 50. Scheiner S (1997) Hydrogen bonding: a theoretical per- ing in liquid water. J Phys Chem Lett 2:2930–2933 spective. Oxford University Press, New York, p 375 33. Kumar S, Pande V, Das A (2012) π-Hydrogen bonding 51. Weller A (1956) Intramolecular proton transfer in wins over conventional hydrogen bonding interac- excited states. Z Elektrochem 60:1144–1147 tion: a jet-cooled study of indole furan heterodimer. 52. Taylor CA, El-Bayoumi MA, Kasha M (1969) Excited- ··· J Phys Chem A 116:1368–1374 state two-proton tautomerism in hydrogen-bonded 34. Mastrorilli P, Gallo V, Todisco S, Latronico M, Saielli N-heterocyclic base pairs. Proc Natl Acad Sci USA G (2016) Uncovering intramolecular π-type hydrogen 63:253–260 bonds in solution by NMR spectroscopy and DFT cal- 53. Sengupta PK, Kasha M (1979) Excited-state proton culations. Chem Eur J 22:7964–7969 transfer spectroscopy on 3-hyroxyfavone and querce- 35. Aliev AE, Arendorf JRT, Pavlakos I, Moreno RB, Por- tin. Chem Phys Lett 68:382–385 ter MJ, Rzepa HS, Motherwell WB (2015) Surfng 54. Chou PT, McMorrow D, Aartsma TJ, Kasha M (1984) π clouds for noncovalent interactions: Arenes versus The proton-transfer laser. Gain spectrum and amplif- alkenes. Angew Chem Int Ed 54:551–555 cation of spontaneous emission of 3-hydroxyfavone. J 36. Grabowski SJ, Sokalski WA, Leszczynski J (2006) Can Phys Chem 88:4596–4599 H…σ, …H …σ and σ…H …σ interactions be 55. Nishiya T, Yamauchi S, Hirota N, Baba M, Hanazaki I π + + classifed as H-bonded? Chem Phys Lett 432:33–39 (1986) Fluorescence studies of the intramolecularly 37. Grabowski SJ (2019) A H…σ hydrogen bonds: hydrogen-bonded molecules o-hydroxyacetophenone − dihydrogen and cycloalkanes as proton acceptors. and salicylamide and related molecules. J Phys Chem ChemPhysChem 20:565–574 90:5730–5735 38. Alkorta I, Elguero J, Bene JED (2010) An ab initio inves- 56. Nagaoka S, Fujita M, Takemura T, Baba H (1986) Flu-

tigation of the properties of H2:HX hydrogen-bonded orescence from an upper excited state of o-hydroxy- complexes. Chem Phys Lett 489:159–163 benzaldehyde in the vapor phase. Chem Phys Lett 39. Grabowski SJ (2013) Dihydrogen bond and X-H…σ 123:123–125 interaction as sub-classes of hydrogen bond. J Phys Org 57. Ernsting NP, Nikolaus B (1986) Dye-laser pulse Chem 26:452–459 shortening by transient absorption following excited- 40. Pirani F, Cappelletti D, Belpassi L, Tarantelli F (2013) state intramolecular proton transfer. Appl Phys B

Intermolecular interaction in the NH 3–H2 and H 2O– 39:155–164

H2 complexes by molecular beam scattering experi- 58. Martinez ML, Cooper WC, Chou P-T (1992) A novel ments: the role of charge transfer. J Phys Chem A excited-state intramolecular proton transfer mol- 117:12601–12607 ecule, 10-hydroxybenzo[h]quinoline. Chem Phys Lett 41. Kvyatkovskaya EA, Nikitina EV, Khrustalev VN, 193:151–154 Galmés B, Zubkov FI, Frontera A (in press) Through 59. Werner T (1979) Triplet deactivation in benzo- space “α-effect” between the O-bridge atoms in triazole-type ultraviolet stabilizers. J Phys Chem diepoxybenzo[de]isothiochromene derivatives. Eur J 83:320–329 Org Chem. https://doi.org/10.1002/ejoc.20190 1169 60. Tarkka RM, Zhang X, Jenekhe SA (1996) Electrically 42. Arunan E, Desiraju GR, Klein RA, Sadlej J, Scheiner generated intramolecular proton transfer: electrolumi- S, Alkorta I, Clary DC, Crabtree RH, Dannenberg JJ, nescence and stimulated emission from polymers. J Am Hobza P, Kjaergaard HG, Legon AC, Mennucci B, Nes- Chem Soc 118:9438–9439 bitt DJ (2011) Defnition of the hydrogen bond. Pure 61. Williams DL, Heller J (1970) Intramolecular proton Appl Chem 83:1637–1641 transfer reactions in excited fuorescent compounds. J 43. Pimentel GC, McClellan AL (1960) The Hydrogen Phys Chem 74:4473–4480 bond. Freeman, San Francisco 62. Heller HJ, Blattmann HR (1973) Some aspects of sta- 44. Vinogradov SN, Linnell RH (1971) Hydrogen bonding. bilization of polymers against light. Pure Appl Chem Van Nostrand-Reinhold, New York 36:141–161

71 J. Indian Inst. Sci. | VOL 100:1 | 61–76 January 2020 | journal.iisc.ernet.in 1 3 S. Scheiner

63. Latajka Z, Scheiner S (1992) Proton transfer in the 78. Forés M, Scheiner S (1999) Effects of chemical substi- ground and frst excited triplet states of malonaldehyde. tution upon excited state proton transfer: fuoroderiva- J Phys Chem 96:9764–9767 tives of salicylaldimine. Chem Phys 246:65–74 64. Luth K, Scheiner S (1994) Excited-state energetics and 79. Yi M, Scheiner S (1996) Proton transfer between phenol proton-transfer barriers in malonaldehyde. J Phys and ammonia in ground and excited electronic states. Chem 98:3582–3587 Chem Phys Lett 262:567–572 65. Yang Y, Li D, Li C, Liu Y, Jiang K (2019) Asymmet- 80. Scheiner S (2000) Theoretical studies of excited state ric substitution changes the UV-induced nonra- proton transfer in small model systems. J Phys Chem A diative decay pathway and the spectra behaviors of 104:5898–5909 β-diketones. Spectrochim Acta Part A Mol Biomol 81. Pang X, Jiang C, Xie W, Domcke W (2019) Photoin- Spectrosc 207:209–215 duced electron-driven proton transfer from water to an 66. Tsutsumi T, Ono Y, Arai Z, Taketsugu T (2018) Visu- N-heterocyclic chromophore: nonadiabatic dynamics alization of the intrinsic reaction coordinate and global studies for pyridine–water clusters. Phys Chem Chem reaction route map by classical multidimensional scal- Phys 21:14073–14079 ing. J Chem Theory Comput 14:4263–4270 82. Pang X, Ehrmaier J, Wu X, Jiang C, Xie W, Sobolewski 67. Zamastil J, Šimsa D (2017) Quantum effects and quan- AL, Domcke W (2018) Photoinduced hydrogen-trans- tum chaos in multidimensional tunneling. Phys Rev E fer reactions in pyridine-water clusters: insights from 96:062201 excited-state electronic-structure calculations. Chem 68. Nandipati KR, Kanakati AK, Singh H, Mahapatra Phys 515:550–556 S (2019) Controlled intramolecular H-transfer in 83. Wu X, Karsili TNV, Domcke W (2017) Role of electron- malonaldehyde in the electronic ground state medi- driven proton-transfer processes in the ultrafast deacti- ated through the conical intersection of 1nπ* and vation of photoexcited anionic 8-oxoGuanine-adenine 1ππ* excited electronic states. Phys Chem Chem Phys and 8-oxoGuanine-cytosine base pairs. Molecules 21:20018–20030 22:135 69. Coe JD, Martínez TJ (2006) Ab initio molecular 84. Trung NT, Khanh PN, Carvalho AJP, Nguyen MT dynamics of excited-state intramolecular proton trans- (2019) Remarkable shifts of Csp2-H and O–H stretch- fer around a three-state conical intersection in malonal- ing frequencies and stability of complexes of formic dehyde. J Phys Chem A 110:618–630 acid with formaldehydes and thioformaldehydes. J 70. Sobolewski AL, Domcke W (1999) Photophysics of Comput Chem 40:1387–1400 malonaldehyde: an ab initio study. J Phys Chem A 85. Bednowitz AL, Post B (1966) Direct determination 103:4494–4504 of the crystal structure of β-fumaric acid. Acta Cryst 71. Luth K, Scheiner S (1995) Proton transfer in ground 21:566–571 and excited electronic states of glyoxalmonohydrazine. 86. Glasstone S (1937) The structure of some molecu- J Phys Chem 99:7352–7359 lar complexes in the liquid phase. Trans Faraday Soc 72. Duan X, Scheiner S (1993) Ground and excited state 33:200–214 intramolecular proton transfer in OCCNN ring. Chem 87. Dippy JFJ (1939) The dissociation constants of mono- Phys Lett 204:36–44 carboxylic acids; Their measurement and their sig- 73. Rovira MC, Scheiner S (1995) Transfer of a pro- nifcance in theoretical organic chemistry. Chem Rev ton between N atoms in excited electronic states of 25:151–211 1,5-diaza-1,3-pentadiene. J Phys Chem 99:9854–9861 88. Sutor DJ (1962) The C-H…O hydrogen bond in crys- 74. Scheiner S, Kar T, Cuma M (1997) Excited state intra- tals. Nature 195:68–69 molecular proton transfer in anionic analogues of 89. Karpfen A (2019) On the interaction of propynal with

malonaldehyde. J Phys Chem A 101:5901–5909 HNO, HF, HCl, H2O, CH 3OH, and NH3: red- and blue- 75. Vener MV, Scheiner S (1995) Hydrogen bonding and shifting hydrogen bonds and tetrel bonds. Comput proton transfer in the ground and lowest excited sin- Theor Chem 1160:1–13 glet states of o-hydroxyacetophenone. J Phys Chem 90. Behera B, Das PK (2019) Blue-shifted hydrogen bond- 99:642–649 ing in the gas phase CH/D3CN HCCl3 complexes. J ··· 76. Cuma M, Scheiner S, Kar T (1999) Effect of adjoin- Phys Chem A 123:1830–1839 ing aromatic ring upon excited state proton transfer. 91. Zhang L, Li D (2019) An insight into intramolecular o-Hydroxybenzaldehyde. J Mol Struct (Theochem) blue-shifting CH hydrogen bonds in 1,3-hexadien- ···π 467:37–49 5-yne and its halogen-substituted derivatives. Chem 77. Vener MV, Scheiner S, Sokolov ND (1994) Theoretical Phys 518:58–68 study of hydrogen bonding and proton transfer in the 92. Scheiner S (2000) CH O hydrogen bonding. In: Harg- ··· ground and lowest excited singlet states of tropolone. J ittai M, Hargittai I (eds) Advances in molecular struc- Chem Phys 101:9755–9765 ture research, vol 6. JAI Press, Stamford, pp 159–207

72 1 3 J. Indian Inst. Sci.| VOL 100:1 | 61–76 January 2020 | journal.iisc.ernet.in The Hydrogen Bond

93. Masunov A, Dannenberg JJ, Contreras RH (2001) 109. Scheiner S (2006) Contributions of NH O and CH O ·· ·· C–H bond-shortening upon hydrogen bond forma- H-bonds to the stability of β-sheets in proteins. J Phys tion: infuence of an electric feld. J Phys Chem A Chem B 110:18670–18679 105:4737–4740 110. Pohl G, Plumley JA, Dannenberg JJ (2013) The interac- 94. Pejov L, Hermansson K (2003) On the nature of tions of phenylalanines in β-sheet-like structures from blueshifting hydrogen bonds: ab initio and density molecular orbital calculations using density functional functional studies of several fuoroform complexes. J theory (DFT), MP2, and CCSD(T) methods. J Chem Chem Phys 119:313–324 Phys 138:245102 95. Qian W, Krimm S (2002) Vibrational spectroscopy 111. Wang C-S, Sun C-L (2010) Investigation on the indi- of hydrogen bonding: origin of the different behav- vidual contributions of N–H O C and C–H O C ··· = ··· = ior of the C-H…O hydrogen bond. J Phys Chem A interactions to the binding energies of β-sheet models. J 106:6628–6636 Comput Chem 31:1036–1044 96. Li X, Liu L, Schlegel HB (2002) On the physical ori- 112. Guo H, Gorin A, Guo H (2009) A peptide-linkage dele- gin of blue-shifted hydrogen bonds. J Am Chem Soc tion procedure for estimate of energetic contributions 124:9639–9647 of individual peptide groups in a complex environ- 97. Alabugin IV, Manoharan M, Peabody S, Weinhold F ment: application to parallel β-sheets. Interdiscip Sci (2003) Electronic basis of improper hydrogen bonding: Comput Life Sci 1:12–20 a subtle balance of hyperconjugation and rehybridiza- 113. Vener MV, Egorova AN, Fomin DP, Tsirel’son VG tion. J Am Chem Soc 125:5973–5987 (2009) A quantum-topological analysis of noncovalent 98. Joseph J, Jemmis ED (2007) Red-, blue-, or no-shift interactions in secondary polyalanine structures. Russ J hydrogen bonds: a unifed explanation. J Am Chem Soc Phys Chem B 3:541–547 129:4620–4632 114. Vener MV, Egorova AN, Fomin DP, Tsirelson VG (2007) 99. Karpfen A, Kryachko ES (2009) On the intramolecular QTAIM study of the closed-shell interactions in peptide origin of the blue shift of A-H stretching frequencies: secondary structures: a cluster treatment of oligo- and triatomic hydrides HAX. J Phys Chem A 113:5217–5223 polyalanines. Chem Phys Lett 440:279–285 100. Grabowski SJ (2011) Red- and blue-shifted hydrogen 115. Parthasarathi R, Raman SS, Subramanian V, Ramasami bonds: the bent rule from quantum theory of atoms in T (2007) Bader’s electron density analysis of hydrogen molecules perspective. J Phys Chem A 115:12789–12799 bonding in secondary structural elements of proteins. J 101. Mo Y, Wang C, Guan L, Braïda B, Hiberty PC, Wu W Phys Chem A 111:7141–7148 (2014) On the nature of blue shifting hydrogen bonds. 116. Scheiner S (2007) The strength with which a pep- Chem Eur J 20:8444–8452 tide group can form a hydrogen bond varies with the 102. Gu Y, Kar T, Scheiner S (1999) Fundamental properties internal conformation of the polypeptide chain. J Phys of the CH …O interaction: Is it a true hydrogen bond? J Chem B 111:11312–11317 Am Chem Soc 121:9411–9422 117. Scheiner S, Kar T (2005) Effect of solvent upon CH O ·· 103. Scheiner S, Gu Y, Kar T (2000) Evaluation of the hydrogen bonds with implications for protein folding. J H-bonding properties of CH …O interactions based Phys Chem B 109:3681–3689 upon NMR spectra. J Mol Struct (Theochem) 118. Scheiner S (2008) Analysis of catalytic mechanism of 500:441–452 serine proteases. Viability of ring-fip hypothesis. J Phys 104. Scheiner S, Grabowski SJ, Kar T (2001) Infuence Chem B 112:6837–6846 of hybridization and substitution upon the proper- 119. Horowitz S, Adhikari U, Dirk LMA, Del Rizzo PA, Mehl ties of the CH O hydrogen bond. J Phys Chem A RA, Houtz RL, Al-Hashimi HM, Scheiner S, Trievel ·· 105:10607–10612 RC (2014) Manipulating Unconventional CH-Based 105. Scheiner S, Kar T (2002) Red versus blue-shifting Hydrogen Bonding in a Methyltransferase via Non- hydrogen bonds: Are there fundamental distinctions? J canonical Amino Acid Mutagenesis. ACS Chem Biol Phys Chem A 106:1784–1789 9:1692–1697 106. Gu Y, Kar T, Scheiner S (2000) Comparison of the 120. Jones CR, Baruah PK, Thompson AL, Scheiner S, Smith CH …N and CH …O interactions involving substituted MD (2012) Can a C-H O interaction be a determinant ··· alkanes. J Mol Struct 552:17–31 of conformation. J Am Chem Soc 134:12064–12071 107. Scheiner S, Kar T, Gu Y (2001) Strength of the C αH.O 121. S. Scheiner, Dissection of the Factors Affecting Forma- hydrogen bond of amino acid residues. J Biol Chem tion of a CH∙∙∙O H-Bond. A Case Study, Cryst. 5, 327 276:9832–9837 (2015) 108. Scheiner S, Kar T, Pattanayak J (2002) Comparison of 122. Driver RW, Claridge TDW, Scheiner S, Smith MD various types of hydrogen bonds involving aromatic (2016) Torsional and Electronic Factors Control the amino acids. J Am Chem Soc 124:13257–13264 C H O Interaction. Chem Eur J 22:16513–16521 − ···

73 J. Indian Inst. Sci. | VOL 100:1 | 61–76 January 2020 | journal.iisc.ernet.in 1 3 S. Scheiner

123. Adhikari U, Scheiner S (2013) The Magnitude and 139. Scheiner S (2011) Effects of multiple substitution Mechanism of Charge Enhancement of CH O upon the P …N noncovalent interaction. Chem Phys ·· H-bonds. J Phys Chem A 117:10551–10562 387:79–84 … 124. B. Nepal and S. Scheiner, Anionic CH X− Hydrogen 140. Scheiner S (2011) Effects of substituents upon Bonds: Origin of Their Strength, Geometry, and Other the P …N noncovalent interaction: the limits of its Properties, Chem. Eur. J. 21, 1474-1481 (2015) strength. J Phys Chem A 115:11202–11209 125. Nepal B, Scheiner S (2015) Microsolvation of Anions 141. Scheiner S (2011) Can two trivalent N atoms engage … by Molecules Forming CH∙∙X− Hydrogen Bonds. Chem in a direct N N noncovalent interaction? Chem Phys Phys 463:137–144 Lett 514:32–35 126. Scheiner S, Kar T (2008) Spectroscopic and struc- 142. Scheiner S (2013) The pnicogen bond: its relation to tural signature of the CH–O H-bond. J Phys Chem A hydrogen, halogen, and other noncovalent bonds. Acc 112:11854–11860 Chem Res 46:280–288 127. Scheiner S (2009) Identifcation of spectroscopic pat- 143. Scheiner S (2013) Detailed comparison of the pni- terns of CH–O H-bonds in dipeptides. J. Phys. Chem. B cogen bond with chalcogen, halogen and hydrogen 113:10421–10427 bonds. Int J Quantum Chem 113:1609–1620 128. Scheiner S (2010) Effect of CH…O hydrogen bond 144. Scheiner S (2011) On the properties of X…N nonco- length on the geometric and spectroscopic features valent interactions for frst-, second- and third-row X of the peptide unit of proteins. Int J Quantum Chem atoms. J Chem Phys 134:164313 110:2775–2783 145. Adhikari U, Scheiner S (2014) Effects of charge and 129. Hassel O (1970) Structural aspects of interatomic substituent on the S N Chalcogen bond. J Phys ··· charge-transfer bonding. Science 170:497–502 Chem A 118:3183–3192 130. Lommerse JPM, Stone AJ, Taylor R, Allen FH (1996) 146. Nziko VDPN, Scheiner S (2014) Chalcogen bonding

The nature and geometry of intermolecular interac- between tetravalent SF4 and amines. J Phys Chem A tions between halogens and oxygen or nitrogen. J Am 118:10849–10856 Chem Soc 118:3108–3116 147. Azofra LM, Alkorta I, Scheiner S (2015) Chalcogen 131. Allen FH, Lommerse JPM, Hoy VJ, Howard JAK, bonds in complexes of SOXY (X, Y F, Cl) with nitro- = Desiraju GR (1997) Halogen…O(nitro) supramolecular gen bases. J Phys Chem A 119:535–541 synthon in crystal engineering: a combined crystallo- 148. Nziko VDPN, Scheiner S (2015) Intramolecular graphic database and ab initio molecular orbital study. S O Chalcogen bond as stabilizing factor in geom- ··· Acta Cryst B53:1006–1016 etry of substituted phenyl-SF3 molecules. J Org Chem 132. Ikuta S (1990) Anisotropy of electron-density distribu- 80:2356–2363 tion around atoms in molecules: N, P, O and S atoms. J. 149. Nziko VDPN, Scheiner S (2015) S Chalcogen ···π Mol. Struct. (Theochem) 205:191–201 bonds between SF2 or SF4 and C–C multiple bonds. J 133. Hathwar VR, Row TNG (2010) Nature of Cl Cl Phys Chem A 119:5889–5897 ··· intermolecular interactions via experimental and 150. Rosenfeld RE, Parthasarathy R, Dunitz JD (1977) theoretical charge density analysis: correlation of Directional preferences of nonbonded atomic con- polar fattening effects with geometry. J Phys Chem A tacts with divalent sulfur. 1. Electrophiles and nucleo- 114:13434–13441 philes. J Am Chem Soc 99:4860–4862 134. Sedlak R, Kolář MH, Hobza P (2015) Polar fattening 151. Burling FT, Goldstein BM (1992) Computational stud- and the strength of halogen bonding. J Chem Theory ies of nonbonded sulfur–oxygen and selenium–oxygen Comput 11:4727–4732 interactions in the thiazole and selenazole nucleosides. J 135. Politzer P, Lane P, Concha MC, Ma Y, Murray JS Am Chem Soc 114:2313–2320 (2007) An overview of halogen bonding. J Mol Model 152. Iwaoka M, Tomoda S (1994) A model study on the 13:305–311 effect of an amino group on the antioxidant activity of 136. Clark T, Hennemann M, Murray JS, Politzer P glutathione peroxidase. J Am Chem Soc 116:2557–2561 (2007) Halogen bonding: the σ-hole. J Mol Model 153. Del Bene JE, Alkorta I, Elguero J (2019) Probing C S ··· 13:291–296 chalcogen bonds in complexes SC:SHX, for X NO , = 2 137. Solimannejad M, Gharabaghi M, Scheiner S (2011) NC, F, Cl, CN, CCH, and NH2. Chem Phys Lett SH …N and SH…P blue-shifting H-Bonds and N…P 721:86–90 interactions in complexes pairing HSN with amines 154. Esrafli MD, Mousavian P, Mohammadian-Sabet F and phosphines. J. Chem. Phys 134:024312 (2019) The infuence of hydrogen- and lithium-bond- 138. Scheiner S (2011) A new noncovalent force: compari- ing on the cooperativity of chalcogen bonds: a compar- son of P…N interaction with hydrogen and halogen ative ab initio study AU—Esrafli, Mehdi D. Mol Phys bonds. J. Chem. Phys 134:094315 117:726–733 155. Alkorta I, Legon A (2018) An ab initio investigation of the geometries and binding strengths of Tetrel-,

74 1 3 J. Indian Inst. Sci.| VOL 100:1 | 61–76 January 2020 | journal.iisc.ernet.in The Hydrogen Bond

Pnictogen-, and chalcogen-bonded complexes of CO2, 171. Grabowski SJ (2015) π-hole bonds: boron and

N 2O, and CS 2 with simple lewis bases: some generaliza- aluminum lewis acid centers. ChemPhysChem tions. Molecules 23:2250 16:1470–1479 156. Gleiter R, Haberhauer G, Werz DB, Rominger F, Blei- 172. Chi Z, Dong W, Li Q, Yang X, Scheiner S, Liu S holder C (2018) From noncovalent chalcogen–chalco- (2019) Carbene triel bonds between TrR3 (Tr B, Al) = gen interactions to supramolecular aggregates: experi- and N-heterocyclic carbenes. Int J Quantum Chem ments and calculations. Chem Rev 118:2010–2041 119:e25867 157. Scheiner S (2015) Comparison of CH O, SH O, 173. Michalczyk M, Zierkiewicz W, Scheiner S (2018) ··· ··· Chalcogen, and Tetrel bonds formed by neutral and Triel-bonded complexes between TrR (Tr B, Al, Ga; 3 = cationic sulfur-containing compounds. J Phys Chem A R H, F, Cl, Br, CH ) and pyrazine. ChemPhysChem = 3 119:9189–9199 19:3122–3133 158. Nziko VDPN, Scheiner S (2016) Comparison of π-hole 174. Mukherjee A, Sanz-Matias A, Velpula G, Waghray D, tetrel bonding with σ-hole halogen bonds in complexes Ivasenko O, Bilbao N, Jeremy N, Harvey K, Mali S, of XCN (X F, Cl, Br, I) and NH . Phys Chem Chem De Feyter S (2019) Halogenated building blocks for = 3 Phys 18:3581–3590 2D crystal engineering on solid surfaces: lessons from 159. Liu M, Li Q, Scheiner S (2017) Comparison of tet- hydrogen bonding. Chem Sci 10:3881–3891 rel bonds in neutral and protonated complexes of 175. Xu C, Loh CCJ (2019) A multistage halogen bond pyridineTF and furanTF (T C, Si, and Ge) with catalyzed strain-release glycosylation unravels new 3 3 = NH 3. Phys Chem Chem Phys 19:5550–5559 hedgehog signaling inhibitors. J Am Chem Soc 160. Scheiner S (2017) Systematic elucidation of factors that 141:5381–5391 infuence the strength of Tetrel bonds. J Phys Chem A 176. Carreras L, Benet-Buchholz J, Franconetti A, Frontera 121:5561–5568 A, van Leeuwen PWNM, Vidal-Ferran A (2019) Halo- 161. Scheiner S (2018) Steric crowding in Tetrel bonds. J gen bonding effects on the outcome of reactions at Phys Chem A 122:2550–2562 metal centres. Chem Commun 55:2380–2383 162. Zierkiewicz W, Michalczyk M, Scheiner S (2018) Impli- 177. Hijazi H, Vacher A, Groni S, Lorcy D, Levillain E, Fave cations of monomer deformation for tetrel and pnico- C, Schöllhorn B (2019) Electrochemically driven inter- gen bonds. Phys Chem Chem Phys 20:8832–8841 facial halogen bonding on self-assembled monolayers 163. Zierkiewicz W, Michalczyk M, Wysokiński R, Scheiner for anion detection. Chem Commun 55:1983–1986 S (2019) Dual geometry schemes in Tetrel bonds: com- 178. Zhang X, Ren J, Tan SM, Tan D, Lee R, Tan C-H (2019) plexes between TF (T Si, Ge, Sn) and pyridine deriv- An enantioconvergent halogenophilic nucleophilic sub- 4 = atives. Molecules 24:376 stitution (S N2X) reaction. Science 363:400–404 164. Trievel RC, Scheiner S (2018) Crystallographic and 179. Wang H, Bisoyi HK, Urbas AM, Bunning TJ, Li Q computational characterization of methyl tetrel bond- (2019) The halogen bond: an emerging supramolecular ing in S-adenosylmethionine-dependent methyltrans- tool in the design of functional mesomorphic materials. ferases. Molecules 23:2965–2981 Chem Eur J 25:1369–1378 165. Scheiner S (2018) Ability of IR and NMR spectral data 180. Liu C-Z, Koppireddi S, Wang H, Zhang D-W, Li Z-T to distinguish between a Tetrel bond and a hydrogen (2019) Halogen bonding directed supramolecular bond. J Phys Chem A 122:7852–7862 quadruple and double helices from hydrogen-bonded 166. Scheiner S (2019) Dependence of NMR chemical shifts arylamide foldamers. Angew Chem Int Ed 58:226–230 upon CH bond lengths of a methyl group involved in a 181. Serpell CJ, Kilah NL, Costa PJ, Félix V, Beer PD Tetrel bond. Chem Phys Lett 714:61–64 (2010) Halogen bond anion templated assembly of 167. Zhang J, Hu Q, Li Q, Scheiner S, Liu S (2019) Compari- an imidazolium pseudorotaxane. Angew Chem Int Ed son of σ-hole and π-hole Tetrel bonds in complexes of 49:5322–5326 borazine with TH3F and F TO/H TO (T C, Si, Ge). 182. Caballero A, White NG, Beer PD (2011) A bidentate 2 2 = Int J Quantum Chem 119:e25910 halogen-bonding bromoimidazoliophane receptor for 168. Zierkiewicz W, Michalczyk M, Scheiner S (2018) Com- bromide ion recognition in aqueous media. Angew parison between Tetrel bonded complexes stabilized by Chem Int Ed Engl 50:1845–1848 σ and π hole interactions. Molecules 23:1416 183. Walter SM, Kniep F, Rout L, Schmidtchen FP, Herdt- 169. Wei Y, Li Q, Scheiner S (2018) The π-tetrel bond and weck E, Huber SM (2012) Isothermal calorimetric titra- its infuence on hydrogen bonding and proton transfer. tions on charge-assisted halogen bonds: role of entropy, ChemPhysChem 19:736–743 counterions, solvent, and temperature. J Am Chem Soc 170. Grabowski SJ (2014) Boron and other triel lewis acid 134:8507–8512 centers: from hypovalency to hypervalency. ChemPhy- 184. Gilday LC, White NG, Beer PD (2013) Halogen- and sChem 15:2985–2993 hydrogen-bonding triazole-functionalised porphyrin- based receptors for anion recognition. Dalton Trans 42:15766–15773

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185. Borissov A, Marques I, Lim JYC, Félix V, Smith MD, 190. Nepal B, Scheiner S (2015) Substituent effects on the bind- Beer PD (2019) Anion recognition in water by charge- ing of halides by neutral and dicationic bis(triazolium) neutral halogen and chalcogen bonding foldamer receptors. J Phys Chem A 119:13064–13073 receptors. J Am Chem Soc 141:4119–4129 191. Nepal B, Scheiner S (2016) Building a better halide 186. Klein HA, Beer PD (2019) Iodide discrimination by receptor: optimum choice of spacer, binding unit, and tetra-iodotriazole halogen bonding interlocked hosts. halosubstitution. ChemPhysChem 17:836–844 Chem Eur J 25:3125–3130 192. Scheiner S (2017) Assembly of effective halide receptors 187. Hein R, Borissov A, Smith MD, Beer PD, Davis JJ (2019) from components. Comparing hydrogen, halogen, and A halogen-bonding foldamer molecular flm for selec- Tetrel bonds. J Phys Chem 121:3606–3615 tive reagentless anion sensing in water. Chem Commun 193. Scheiner S (2017) Comparison of halide receptors 55:4849–4852 based on H, halogen, chalcogen, pnicogen, and tetrel 188. Chakraborty S, Maji S, Ghosh R, Jana R, Datta A, Ghosh bonds. Faraday Disc 203:213–226 P (2019) Aryl-platform-based tetrapodal 2-iodo-imida- 194. Scheiner S (2018) Tetrel bonding as a vehicle for strong zolium as an excellent halogen bond receptor in aque- and selective anion binding. Molecules 23:1147–1155 ous medium. Chem Commun 55:1506–1509 195. Scheiner S (2019) Differential binding of tetrel-bonding 189. Nepal B, Scheiner S (2015) competitive halide binding bipodal receptors to monatomic and polyatomic ani- by halogen versus hydrogen bonding: bis-triazole pyri- ons. Molecules 24:227 dinium. Chem Eur J 21:13330–13335

Steve Scheiner is a professor of computational chemistry at Utah State University. After receiving his Ph.D. from Harvard University in 1976, and proceeding to a Weizmann Postdoctoral Fellowship at Ohio State Uni- versity, he started his independent academic career at Southern Illinois University, Carbondale. He moved to Utah State University in 2000. His research has centered around various aspects of H-bonds, from their fundamental underpinning to their role in enzymatic activity, from the proton transfers that take place within to their cousins, known as halogen, chalcogen, pnicogen, and tetrel bonds.

76 1 3 J. Indian Inst. Sci.| VOL 100:1 | 61–76 January 2020 | journal.iisc.ernet.in