Hydrogen bonding and other weak interactions in biopolymers
Jiří Kozelka
Université Paris Descartes
Laboratoire de Chimie et Biochimie Pharmacologiques et
Toxicologiques
UMR CNRS 8601
45 rue des Saints-Pères
75270 Paris FRANCE
and
Masaryk University in Brno
Institute of Condensed Matter Physics
Kotlářská 2
61137 Brno, Czech Republic
‘‘a type of dipole–dipole interaction’’ (Brown et al.: Chemistry: The Central
Science, 12th edn, Prentice Hall: Upper Saddle River, NJ 2012)
‘‘a special type of dipole–dipole interaction’’ (Burdge: Chemistry, 2nd edn,
McGraw-Hill: Boston, MA 2011)
‘‘particularly strong dipole–dipole forces’’ (Zumdahl and Zumdahl: Chemistry:
An Atoms First Approach, Brooks Cole: Belmont, CA 2012)
‘‘an extreme form of dipole–dipole interaction’’ (Kotz et al.: Chemistry and
Chemical Reactivity, 7th edn, Brooks Cole: Belmont, CA 2009)
‘‘especially enhanced dipole–dipole forces’’ (Siska: University Chemistry,
Prentice-Hall: Upper Saddle River, NJ 2005),
‘‘a special kind of dipole–dipole force’’ (Moore et al.: Chemistry: The
Molecular Science, 4th edn, Brooks-Cole: Belmont, CA, 2010)
‘‘a sort of super dipole–dipole force’’ (Tro: Chemistry: A Molecular Approach,
2nd edn, Prentice-Hall: Boston, MA 2011)
“no more than a particularly strong type of directional dipole-dipole
interaction” (J. Israelachvili: Intermolecular and Surface Forces, 2nd ed.,
Academic Press, New York (1991)
What is a hydrogen bond? Textbook definitions
Wikipedia (2014):
‘‘The hydrogen bond is the electromagnetic attractive interaction between
polar molecules. . . it is not a true bond but a particularly strong dipole–
dipole attraction, and should not be confused with a covalent bond’’.
Vodíková vazba (vodíkový můstek)
má často silnou elektrostatickou složku:
Xδ--Hδ+ .... :YδX
--- elektronegativní prvek
N,O,F,S,Cl : vazba X-H je polární, na H parciální kladný náboj
Y --- nositel parciálního záporného náboje ve volném elektronovém páru
v biologických makromolekulách hlavně O,N
příklad: vodíkové můstky svazují páry bazí DNA:
N
N
N
N N
H
H
N
N
O
H
O
A
T
N
N
N
N O
N H
H
H
N
N
O
N
H
H
G
C
Vodíkové můstky určují krystalovou strukturu ledu.
Maximalizace počtu vodíkových můstků vede k poměrně malé hustotě
 Led plave na vodě
 Kanálky v mřížce ledu může difundovat kyslík
 Vodíkové můstky mají zásadní význam pro život na Zemi.
http://m.eb.com/
http://chem.ps.uci.edu/
liquid (water) solid (ice)
Projevy přítomnosti vodíkové vazby v kapalinách
- vzrůst bodu varu :
relativní molekulová hmotnost
Bod varu [K]
Adaptace z http://www.natur.cuni.cz/anorchem/Lukes/k2.pps
Show B-DNA pdb code 3BSE
Highlight resid 13 and 26
The Base Pair Directory
I. Tinoco, Jr. In Appendix 1
of:The RNA World , Cold Spring
Harbor Laboratory Press, 1993,
pp. 603-607.
Oblouky označují atomy
nacházející se ve velkém
žlábku kanonické B-DNA.
Tmavá barva: pohled ze
strany 5´ na nukleotid anti
Světlá barva: pohled ze
strany 3´ na nukleotid anti
Červená:puriny
Zelená: pyrimidiny
paralelní řetězce nebo anti-syn konformace cukrů
antiparalelní řetězce, anti-anti konformace cukrů
purin se páruje atomy 6, 7
paralelní řetězce antiparalelní řetězce
jako W-C jako Rev. W-C
http://jenalib.fli-leibniz.de/ImgLibDoc/bp/pu_py.html
Cvičení: vyzačte zóny velkého a malého žlábku a pomocí modelu B-DNA
určete, zda na bázi nahlížíme ze strany 5´ nebo 3´.
G
G
H
H
G-G Hoogsteen C-C+ pair (in i-motifs)
pKa of N3 of cytosine is 4.7.
Wikipedia
DNA Molecular Motor Driven Micromechanical Cantilever Arrays
http://www.chemguide.co.uk/organicprops/aminoacids/proteinstruct.html
Classical hydrogen bonds stabilizing canonical protein structures
N-HO=C
a-helix b-sheet
Geotrichum lipase (1THG)
antiparallel b-sheet a-helix
Myoglobin (1MBA)
PNAS, 98, 2001, 9057
Crystal structure of uracil
N-HO
C-HO
Extensive CHO hydrogen bonding in the DNA i-motif in an RNA G4 tetraplex
Crystal structure of intercalated fourstranded
d(C3T) at 1.4 A resolution
A. Rich et al., PNAS 91, 1994, 11636
X-ray analysis of an RNA tetraplex
(UGGGGU)4 at 0.6 A resolution
M. Sundaralingam et al., PNAS 98, 2001, 13665
N-Hp hydrogen bonds in protein crystal structures
Bovine pancreatic trypsin inhibitor
Pdb code 5pti
B28Asp insulin
Pdb code 1zeg
X-Hp hydrogen bonds
International Union of Pure and Applied Chemistry (IUPAC) Compendium of
Chemical Terminology (1997):
‘‘. . . a form of association between an electronegative atom and a hydrogen
atom attached to a second, relatively electronegative atom. It is best
considered as an electrostatic interaction, heightened by the small size of
hydrogen, which permits proximity of the interacting dipoles or charges.“
However,….
Dingley and Grzesiek observe J coupling between two 15N nuclei (2JNN) connected
through an H bond, N–H-----N, in nucleic acid–base pairs
 Evidence for orbital overlap and thus support for covalent component of H-bonding
J. Am. Chem. Soc., 1998, 120, 8293.
 8Hz
Note: 2JPtH accross PtH hydrogen bonds were reported many years before, but the
work of Dingley & Grzesiek is widely quoted as the 1st NMR evidence for H-bond
covalency.
Albinati A, Pregosin PS et al. Inorg Chem 26:503 (1987)
Covalency of the Hydrogen Bond in Ice: A Direct X-Ray Measurement
E. D. Isaacs, A. Shukla, P. M. Platzman, D. R. Hamann, B. Barbiellini, and C. A. Tulk,
Phys. Rev. Lett. 82, 600 (1999)
Periodic intensity variations in the measured Compton profile anisotropies of
ordinary ice Ih correspond to distances of 1.72 and 2.85 Å, which are close to the
hydrogen bond length and the nearest O-O distance, respectively. We interpret this as
direct evidence for the substantial covalent nature of the hydrogen bond. Very good
quantitative agreement between the data and a fully quantum mechanical bonding
model, and the disagreement with a purely electrostatic (classical) bonding model
support this interpretation.
25 structures studied by X-ray or
neutron diffraction
Effect of O-HO H-bond formation:
d1 shortens
d2 lengthens
d3 shortens
d4 lengthens
ALL VERIFIED!
O-HO H-bond has a covalent component!
Real-Space Identification of Intermolecular Bondingwith
Atomic Force Microscopy
Jun Zhang, Pengcheng Chen, Bingkai Yuan, Wei Ji, Zhihai Cheng, Xiaohui Qiu, Science 342, 611 (2013)
Hydroxychinolin
na krystalech mědi
B3LYP/aug-cc-pVTZ
Weinhold & Klein, Mol. Phys. 110: 565 (2012)
Korelace mezi celkovou energií H-můstků s jejich kovalentní složkou
 Kovalentní složka je charakteristická vlastnost všech H-můstků
vodíkový můstek
• zvláštní interakce
• důsledek struktury vodíkového atomu:
neobsazuje p-orbitály, nemůže nést volný
(nevazebný) elektronový pár, může se jiným atomům
více přiblížit
• Má několik složek:
- kovalentní spojenou s přenosem náboje z volného el.
páru akceptoru do antivazebného orbitálu donoru X-H
- elektrostatickou, která u silných H-můstků převažuje
- indukční (dipól X-H polarizuje A)
- disperzní (všudypřítomná)
- proti těmto složkám působí překryvová repulze
X-H---A
akceptor A má vždy volný elektronový pár
atom X je většinou silně elektronegativní
Cation-p interactions in protein-protein interfaces
isoprenyl diphosphate synthase (1uby)
Ran-importin beta (1ibr)
(Ran is a GTPase that regulates diverse
cellular processes, including nuclear
transport and mitotic spindle assembly.
Importin-β Is a GDP-to-GTP Exchange
Factor of Ran.)
X-ray structures (1.9-2.2 Å)
of Engrailed homeodomain,
Luisi et al.,1998-2003
Lp-p interaction
responsible for
fluorescence quenching
of trp
Experimental observations of « lone-pair-p interactions»
X-ray structures (0.9-1.0 Å)
of Z-DNA duplexes, Rich et
al., reanalyzed by Egli &
Gessner (Proc. Nat. Acad.
Sci. USA 1995, 92, 180)
Lp-p interaction
responsible for stability of
the left-handed helix
Kozelka et al. (J.Inorg.Biochem.
2012, 108, 69): Re-analysis of
the X-ray structure (1.63 Å) of a
cisplatin-DNA interstrand crosslink
Coste et al.(Nucleic Acids Res.
1999, 27, 1837).
Lp-p interaction
overcompensates O···O
repulsion!
J. K. Kochi et al., Angew. Chem. Int. Ed.
2004, 43, 4650, CSD code LAGYIC
Charge-transfer complexes between
halides and p-receptors observed in
solution and solid state
Unconventional Interactions Between
Water and Heterocyclic Nitrogens in
Protein Structures
B. F. Luisi et al., Proteins,: Structure,
Function, and Bioinformatics 57:1–8 (2004)
Engrailed homeodomain, WT, K52A, K52E
pdb codes 1ENH, 1P7I, 1P7J)
TCP-Br- interaction in solid state
3.2 Å
Charge transfer involvedCharge transfer involved?
Conclusion of the ab initio analyses
TCB interacts with Cl-, forming a strong charge-transfer complex
(DEint  -30 kcal/mol). The large charge-transfer stabilization energy
arises from two properties of this interacting couple:
- the small energy gap beween electron donor and acceptror orbitals
- the large overlap between them
In contrast, the interacting couple water-indole shows a large gap
between the water lone-pair and the lowest p* orbital of indole, in
addition, their overlap is small. As a result, the charge-transfer
stabilization in this couple is 1-2 orders of magnitude smaller.
In addition to the large CT component, the TCB - Cl- couple profits
from a larger electrostatic component, arising from the interaction
between the net charge of chloride with the electropositive region
around the C-H bonds of TCB.
Take-home message
Structures of nucleic acids and proteins are stabilized by a number
of weak interactions. These include:
- Hydrogen bonds
- Cation-p interactions
- Lone-pair-p interactions
Hydrogen bonds are not only electrostatic interacitons between
dipoles. They contain also a covalent component, which is present
in all hydrogen bonds.
C-HO and X-Hp hydrogen bonds (X = N, O, C) are important
interactions stabilizing biopolymers.