Six Pyranoside Forms of Free 2-Deoxy-D-ribose

Peña, I.; Cocinero, E. J.; Cabezas, C.; Lesarri, A.; Mata, S.; Écija, P.; Daly, A. M.; Cimas, Á.; Bermúdez, C.; Basterretxea, F. J.; Blanco, S.; Fernández, J. A.; López, J. C.; Castaño, F.; Alonso, J. L.  Angew. Chem. Int. Ed. 2013, 52, 11840-11845
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

2-deoxyribose 1 is undoubtedly one of the most important sugars as it is incorporated into the backbone of DNA. The conformational landscape of 1 is complicated: it can exist as an open chain, as a five-member ring (furanose), or a six-member ring (pyranose), and intramolecular hydrogen bonding can occur. This internal hydrogen bonding is in competition with hydrogen bonding to water in aqueous solution. Unraveling all this is of great interest in predicting structures of this and a whole host of sugar and sugar containing-molecules.

1

In order to get a firm starting point, the gas phase structures of the low energy conformers of 1 would constitute a great set of structures to use as a benchmark for gauging force fields and computational methods. Cocinero and Alonso¹ have performed a laser ablation molecular beam Fourier transform microwave (LA-MB-FTMW) experiment (see these posts for other studies using this technique) on 1 and identified the experimental conformations by comparison to structures obtained at MP2/6-311++G(d,p). Unfortunately the authors do not include these structures in their supporting materials, so I have optimized the low energy conformers of 1 at ωB97X-D/6-31G(d) and they are shown in Figure 1.

1a (0.0)	1b (4.7)
1c (3.3)	1d (5.6)
1e (8.9)	1f (9.4)

Figure 1. ωB97X-D/6-31G(d) optimized structures of the six lowest energy conformers of 1. Relative free energy in kJ mol^-1.

The computed spectroscopic parameters were used to identify the structures responsible for the six different ribose conformers observed in the microwave experiment. To give a sense of the agreement between the computed and experimental parameters, I show these values for the two lowest energy conformers in Table 1.

Table 1. MP2/6-311++G(d,p) computed and observed spectroscopic parameters for the two lowest energy conformers of 1.

	1a		1c
	Expt	Calc	Expt	Calc
A(MHz)	2484.4138	2492	2437.8239	2447
B (MHz)	1517.7653	1533	1510.7283	1527
C (MHz)	1238.9958	1250	1144.9804	1158
ΔG (kJ mol-1)		0.0		3.3

This is yet another excellent example of the symbiotic relationship between experiment and computation in structure identification.

References

(1) Peña, I.; Cocinero, E. J.; Cabezas, C.; Lesarri, A.; Mata, S.; Écija, P.; Daly, A. M.; Cimas, Á.; Bermúdez, C.; Basterretxea, F. J.; Blanco, S.; Fernández, J. A.; López, J. C.; Castaño, F.; Alonso, J. L. "Six Pyranoside Forms of Free 2-Deoxy-D-ribose," Angew. Chem. Int. Ed. 2013, 52, 11840-11845, DOI:10.1002/anie.201305589.

InChIs

1a: InChI=1S/C5H10O4/c6-3-1-5(8)9-2-4(3)7/h3-8H,1-2H2/t3-,4+,5-/m0/s1
InChIKey=ZVQAVWAHRUNNPG-LMVFSUKVSA-N

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Computation-aided structure determination

(1) Jahn, M. K.; Dewald, D.; Vallejo-López, M.; Cocinero, E. J.; Lesarri, A.; Grabow, J.-U. "Rotational Spectra of Bicyclic Decanes: The Trans Conformation of (-)-Lupinine," J. Phys. Chem. A 2013
(2) Shepherd, D. J.; Broadwith, P. A.; Dyson, B. S.; Paton, R. S.; Burton, J. W. "Structure Reassignment of Laurefurenynes A and B by Computation and Total Synthesis," Chem. Eur. J. 2013, 19, 12644-12648

Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

I have not discussed any papers that utilize computations to confirm chemical structure in a while, so here are two recent examples.

Grabow has utilized MP2 and M06-2x computations to confirm the lowest energy conformation of (-)-lupinine 1.¹ The interesting structural aspect of this compound is the possibility of an intramolecular hydrogen bond linking the hydroxyl group with the amine.

1

Using molecular mechanics, the authors identified 57 structures within 50 kJ mol^-1 of each other. These geometries were reoptimized at MP2/6-311++G(d,p) and M06-2x/6-311++G(d,p).

The lowest energy structures had the expected trans ring fusion, with a trans relationship between the hydrogen on the bridgehead carbon (C9) and the hydroxymethyl group. This corresponds to either the (R,R) or (S,S) isomer. The three lowest energy structures are shown in Figure 1. Unfortunately, the geometry for the lowest energy isomer provided in the Supporting Materials is wrong, and the authors did not supply the geometries of the other isomers. This situation is unacceptable! Reviewers and editors must do a better job in policing the Supporting Materials; there is no excuse for not including all of the optimized structures, and better yet, in a more usable format that what has been done here. I have reoptimized these structures at M06-2x/6-31G(d). The lowest energy conformer 1a does possess the expected internal hydrogen bond.

1a (0.0)
1b (10.4)	12 (11.5)

Figure 1. M06-2x/6-31G(d) optimized structures of the three lowest energy conformers of 1, with relative free energies in kJ mol^-1.

Table 1 provides a comparison of the MP2 computed values of important structural parameters along with the experimental values obtained from a microwave experiment. The agreement with the computed values for 1a provides strong evidence that this is the structure of (-)-lupinine.

Table 1. Comparison of MP2 and experimental structural parameters of 1.^a

	Expt. (1)	MP2 (1a)
A	1414.126	1425.8
B	811.672	815.1
C	671.530	677.1
ΔJ	0.0255	0.023
ΔJK	0.0639	0.065
ΔK	0.0037	0.0022
χaa	1.9973	2.0
χbb	1.062	1.1
χcc	-3.059	-3.1

^aRotational constants (A, B, C) in MHz, centrifugal distortion constants (Δ_J, Δ_JK, Δ_K) in kHz, and nuclear quadrupole coupling tensor elements (χ_aa, χ_bb, χ_cc) in MHz.

The second study utilizes computed NMR chemical shifts to discriminate potential diastereomeric structures. Laurefurenyne A was first assigned the structure 2 based on 1D and 2D NMR experiments. However, based on potential biochemical analogy to other compounds, Paton and Burton² had doubts about this structure. In addition to synthesizing the natural material, they performed an extensive computational study of the chemical shifts of the diastereomers. For each of the 32 possible diastereomers, they performed a Monte Carlo search of the conformational space using molecular mechanics. The structures of all isomers within 10 kJ mol^-1 of the lowest energy structure were reoptimized at ωB97X-D/6-31G(d) with PCM (CHCl₃) and chemical shifts obtained at mPW1PW91/6-311G(d,p). Final chemical shifts were obtained using a Boltzmann weighting. The computed values for 2were quite off from the experimental values, with a mean unsigned error of 1.5 ppm. A better assessment was provided with the DP4 method, which indicated that 3 has the highest probability of being the correct structure, a structure consistent with the likely biosynthetic pathway.

2

3

References

(1) Jahn, M. K.; Dewald, D.; Vallejo-López, M.; Cocinero, E. J.; Lesarri, A.; Grabow, J.-U. "Rotational Spectra of Bicyclic Decanes: The Trans Conformation of (-)-Lupinine," J. Phys. Chem. A 2013, DOI:10.1021/jp407671m.

(2) Shepherd, D. J.; Broadwith, P. A.; Dyson, B. S.; Paton, R. S.; Burton, J. W. "Structure Reassignment of Laurefurenynes A and B by Computation and Total Synthesis," Chem. Eur. J. 2013, 19, 12644-12648, DOI: 10.1002/chem.201302349.

InChIs

(-)-Lupinine 1: InChI=1S/C11H21NO/c1-11-6-2-3-7-12(11)8-4-5-10(11)9-13/h10,13H,2-9H2,1H3/t10-,11+/m0/s1
InChIKey=WVDUAOYJLFVEMW-WDEREUQCSA-N

Laurefurenyne A 3: InChI=1S/C14H20O4.C2H6/c1-3-4-5-6-12-11(16)8-14(18-12)13-7-10(15)9(2)17-13;1-2/h1,4-5,9-16H,6-8H2,2H3;1-2H3/b5-4-;/t9-,10-,11-,12+,13-,14+;/m1./s1
InChIKey=ZYESDGGYHKCHMJ-SKFGUVSTSA-N

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Comparison of Molecular Mechanics, Semi-Empirical Quantum Mechanical, and Density Functional Theory Methods for Scoring Protein−Ligand Interactions

Nusret D. Yilmazer and Martin Korth Journal of Physical Chemistry B 2013, 117, 8075
Contributed by +Jan Jensen

This paper provides an extremely thorough comparison of electronic protein-ligand interaction energies computed using MM force fields, semi-empirical methods, and DFT.

About 700 protein-ligand complexes were selected from the PDBbind2007 database and four model systems of increasing size (including atoms up to 10 Å from a ligand atom) are created for each. DFT calculations were only possible for around 500 complexes using a 5 Å cutoff, and MM calculations were only possible for 352 complexes due to parameterization problems. 

Single point energies for the protein-ligand complex and separated protein and ligand are then computed and used to compute interaction energies, which were then compared amongst each other.  For example, systems of different size and be compared to monitor convergence and different methods can be compared for a given cutoff.  

Some of the more interesting comparisons to me are PM6-DH+ vs BP86-D2/TZVP (R = 1.00) and MMFF94 vs BP86-D2/TZVP (R = 0.93).  (Interestingly, the former value decreases to 0.92 if COSMO is included - that is unexpected to me.)  While these R values are quite good the corresponding MAD values are quite bad: 14 and 57 kcal/mol, respectively!  I find the former quite surprising since the error in the PM6-DH+ hydrogen bond strengths computed for the underlying training set are on the order of 2 kcal/mol. It could be non-additivity or more interactions between charged groups in the present set.

Acknowledgement: thanks to +Jimmy Charnley Kromann for alerting me to this paper

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Predicting Kinetically Unstable C-C Bonds from the Ground-State Properties of a Molecule

Markopoulos, G.; Grunenberg, J. Angew. Chem. Int. Ed. 2013, 52, 10648
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

Can one identify a labile bond in a molecule without computing activation barriers? Markopoulos and Grunenberg suggest that examination of the bond length and its associated relaxed force constant might provide some guidance.¹

The relaxed force constant comes from identifying the force constant for some coordinate while allowing for other coordinates to relax. Badger’s rule relates the (normal) force constant to bond distance (k = a/(r_eq – d)³). For a series of 36 molecules, covering 71 C-C single bonds, Badger’s rule fits the data well, except for a set of molecules which undergo rapid Cope rearrangements (like bullvalene and semibullvalene). For these molecules, the relaxed force constants are much lower than Badger’s rule predicts, and indicates a weakened bond. This gives rise to their low activation barriers.

Another example is provided with the highly strained polycyclic hydrocarbon 1. This compound is predicted (B3LYP/6-31G(d)) to undergo a [1,2]-shift to give the carbene 2 (see Figure 1), and this is extremely exothermic: -105.7 kcal mol^-1, reflecting the enormous strain of 1. The barrier, through TS1 (Figure 1), is only 6.7 kcal mol^-1. This rearrangement was predicted by examining the relaxed force constants which identified a very weak bond, despite a short bond distance of 1.404 Å. It is unlikely that without this guidance, one would have predicted that this short bond is likely to rupture and produce this particular product.

1	2
TS1

Figure 1. B3LYP/6-31G(d) optimized structures of 1, 2, and TS1.

References

(1) Markopoulos, G.; Grunenberg, J. "Predicting Kinetically Unstable C-C Bonds from the Ground-State Properties of a Molecule," Angew. Chem. Int. Ed. 2013, 52, 10648-10651, DOI: 10.1002/anie.20130382.

InChIs

1: InChI=1S/C14H12/c1-2-8-11-5-3-9-7(1)10(9)4-6-12(8,11)14(8,11)13(7,9)10/h1-6H2
InChIKey=LNBZAENQMFDBJW-UHFFFAOYSA-N

2: InChI=1S/C14H12/c1-3-11-12-4-2-9-7-8(1,9)10(9)5-6-13(11,12)14(10,11)12/h1-6H2
InChIKey=UKVODHRLGFPZPT-UHFFFAOYSA-N

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Tunneling control of chemical reactions: C-H insertion versus H-tunneling in tert-butylhydroxycarbene

Ley, D.; Gerbig, D.; Schreiner, P. R. Chem. Sci. 2013, 4, 677
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

Sorry I missed this paper from much earlier this year – it’s from a journal that’s not on my normal reading list. Anyways, here is another fantastic work from the Schreiner lab demonstrating the concept of tunneling control (see this post).¹ They prepare the t-butylhydroxycarbene 1 at low temperature to look for evidence of formation of possible products arising from a [1,2]-hydrogen shift (2), a [1,2]-methyl shift (3) or a [1,3]-CH insertion (4).

Schreiner performed CCSD(T)/cc-pVDZ optimizations of these compounds along with the transition states for the three migrations. The optimized geometries and relative energies are shown in Figure 1. The thermodynamic product is the aldehyde 2 while the kinetic product is the cyclopropane 4, with a barrier of 23.8 kcal mol^-1 some 3.5 kcal mol^-1 lower than the barrier leading to 2.

1 (0.0)	TS2 (27.3)	2 (-53.5)
	TS3 (31.0)	3 (-41.0)
	TS4 (23.8)	4 (-28.3)

Figure 1. CCSD(T)/cc-pVDZ optimized structures of 1-4 and the transition states for the three reaction. Relative energies in kcal mol^-1.

At low temperature (11 K), 1 is found to slowly convert into 2 with a half-life of 1.7 h. No other product is observed. Rates for the three reactions were also computed using the Wentzel-Kramers-Brillouin (WKB) method (which Schreiner and Allen have used in all of their previous studies). The predicted rate for the conversion of 1 into 2, which takes place at 11 K solely through a tunneling process, is 0.4h, in quite reasonable agreement with experiment. The predicted rates for the other two potential reactions at 11 K are 10³¹ and 10⁴⁰ years.

This is clearly an example of tunneling control. The reaction occurs not across the lowest barrier, butthrough the narrowest barrier.

References

(1) Ley, D.; Gerbig, D.; Schreiner, P. R. "Tunneling control of chemical reactions: C-H insertion versus H-tunneling in tert-butylhydroxycarbene," Chem. Sci. 2013, 4, 677-684, DOI: 10.1039/C2SC21555A.

InChI

1: InChI=1S/C5H10O/c1-5(2,3)4-6/h6H,1-3H3
InChIKey=ZGFKBRGJTPEEOC-UHFFFAOYSA-N

2: InChI=1S/C5H10O/c1-5(2,3)4-6/h4H,1-3H3

3: InChI=1S/C5H10O/c1-4(2)5(3)6/h6H,1-3H3
InChIKey=BZAZNULYLRVMSW-UHFFFAOYSA-N

4: InChI=1S/C5H10O/c1-5(2)3-4(5)6/h4,6H,3H2,1-2H3
InChIKey=MWWQKEGWQLBJBJ-UHFFFAOYSA-N

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Dispersion-Driven Conformational Isomerism in σ-Bonded Dimers of Larger Acenes

Ehrlich, S.; Bettinger, H. F.; Grimme, S. Angew. Chem. Int. Ed. 2013, 41, 10892
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission
The role of dispersion in large systems is increasingly recognized as critical towards understanding molecular geometry. An interesting example is this study of acene dimers by Grimme.¹ The heptacene and nonacene dimers (1 and 2) were investigated with an eye towards the separation between the “butterfly wings” – is there a “stacked” conformation where the wings are close together, along with the “open” conformer?

1

2

The LPNO-CEPA/CBS potential energy surface of 1 shows only a single local energy minima, corresponding to the open conformer. B3LYP-D3 and B3LYP-NL, two different variations of dealing with dispersion (see this post), do a reasonable job at mimicking the LPNO-CEPA results, while MP2 indicates the stacked conformer is lower in energy than the open conformer.

B3LYP-D3 predicts both conformers for the nonacene dimer 2, and the optimized structures are shown in Figure 2. The stacked conformer is slightly lower in energy than the open one, with a barrier of about 3.5 kcal mol^-1. However in benzene solution, the open conformer is expected to dominate due to favorable solvation with both the interior and exterior sides of the wings.

open

stacked

Figure 1. B3LYP-D3/ef2-TZVP optimized structures of the open and stacked conformations of 2.

References

(1) Ehrlich, S.; Bettinger, H. F.; Grimme, S. "Dispersion-Driven Conformational Isomerism in σ-Bonded Dimers of Larger Acenes," Angew. Chem. Int. Ed. 2013, 41, 10892–10895, DOI:10.1002/anie.201304674.

InChIs

1: InChI=1S/C60H36/c1-2-10-34-18-42-26-50-49(25-41(42)17-33(34)9-1)57-51-27-43-19-35-11-3-4-12-36(35)20-44(43)28-52(51)58(50)60-55-31-47-23-39-15-7-5-13-37(39)21-45(47)29-53(55)59(57)54-30-46-22-38-14-6-8-16-40(38)24-48(46)32-56(54)60/h1-32,57-60H
InChIKey=OYVUURMCCBPDLI-UHFFFAOYSA-N

2: InChI=1S/C76H44/c1-2-10-42-18-50-26-58-34-66-65(33-57(58)25-49(50)17-41(42)9-1)73-67-35-59-27-51-19-43-11-3-4-12-44(43)20-52(51)28-60(59)36-68(67)74(66)76-71-39-63-31-55-23-47-15-7-5-13-45(47)21-53(55)29-61(63)37-69(71)75(73)70-38-62-30-54-22-46-14-6-8-16-48(46)24-56(54)32-64(62)40-72(70)76/h1-40,73-76H
InChIKey=FTSMWBVFVPAXOB-UHFFFAOYSA-N

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Intrinsic Atomic Orbitals: An Unbiased Bridge between Quantum Theory and Chemical Concepts

Gerald Knizia J. Chem. Theory Comput. doi:10.1021/ct400687b (Article ASAP)
Contributed by J. Grant Hill.

Readers of Computational Chemistry Highlights are already aware of the power of quantum chemistry in determining/predicting physical observables, but familiar chemical concepts (including the covalent bond!) are, at best, loosely defined in quantum mechanics. This is neatly summarised in Knizia's paper:

"quantum chemistry methods can determine benzene's heat of formation with an accuracy of <2 kJ/mol; but, strictly speaking, they can neither determine the partial charges on benzene's carbon atoms, nor can they show that benzene has twelve localized sigma-bonds and a delocalized pi-system."

 A number of techniques including the quantum theory of atoms in molecules [1], natural bond orbitals [2] and modern valence bond theory [3], to name just a few, have all sought to connect quantum mechanics with concepts known to all chemists, including partial charges, electronegativity, Lewis structures etc. All have been successful to some degree, but often include some assumptions or have complicated programs that require specialist knowledge to run and interpret.

This work by Knizia defines a new method of intrinsic atom orbitals (IAOs) that can exactly express the occupied MOs of an accurate wave function. This is then combined with an orbital localization procedure to construct bond orbitals (IBOs). It is demonstrated that this method is insensitive to basis set size (unlike Mulliken charges), correctly predicts differences in electronegativities, produces the "correct" bond orbitals for some nontrivial cases and can calculate oxidation states of transition-metal complexes (building upon the work of Sit et al.[4]).

This initial implementation of the method shows great promise as an additional tool in the translation of quantum mechanical results into the chemical vernacular, and it will be interesting to observe how it may be applied. My own attraction to the method is due to it combining simplicity of approach with the natural emergence of Lewis structures in the absence of any bias/assumption.

Footnote: The IAO/IBO method will be included in the next public release of the MOLPRO program package, and a sample python implementation will be made available on the author's website (it had not yet been uploaded at the time of writing). Algorithm details are included in an appendix.

References

[1] R. F. W. Bader. A quantum theory of molecular structure and its applications. Chem. Rev. 1991, 91, 893.

[2] E. D. Glendening, C. R. Landis and F. Weinhold. Natural Bond Orbital Methods. WIREs Comput. Mol. Sci. 2012, 2, 1.

[3] J. Gerratt, D. L. Cooper, P. B. Karadakov and M. Raimondi. Modern valence bond theory. Chem. Soc. Rev. 1997, 26, 87; S. Shaik and P. C. Hiberty. A primer on qualitative valence bond theory - a theory coming of age. WIREs Comput. Mol. Sci. 2011, 1, 18.

[4] P. H.-L. Sit, R. Car, M. H. Cohen and A. Selloni. Simple, Unambiguous Theoretical Approach to Oxidation State Determination via First-Principles Calculation. Inorg. Chem. 2011, 50, 10259.

Computer Simulation and Analysis of the Reaction Pathway of Triosephosphate Isomerase

P. A. Bash, M. J. Field, R. C. Davenport, G. A. Petsko, D. Ringe, and M. Karplus Biochemistry 1991, 30, 5826

Contributed by +Jan Jensen 

In honor of the 2013 Nobel Prize in Chemistry I am highlighting this gem from 22 years ago by Karplus and co-workers.  I believe (correct me if I'm wrong) that this paper presents the first study of enzyme catalysis using "conventional" QM/MM: conventional electronic structure theory (AM1) combined with a standard protein force field (CHARMM).    

When the paper came out I had recently started as a PhD student and one of my projects was working on the Effective Fragment Potential QM/MM method.  At that time it was relatively easy to keep track of the QM/MM literature and two papers were usually on top of my rather short stack of QM/MM papers: Singh & Kollman and Field, Bash & Karplus.  As I remember it, I was reading them during an extended visit to the Center for Advanced Research in Biotechnology in Maryland and sitting there it was pretty hard to imagine, based on the applications in these papers, how QM/MM would ever help advance research in biotechnology.  There was a hint in the Field, Bash, and Karplus paper, where they used something called Triose Phosphate Isomerase (TIM) to motivate the use of link atoms, but it wasn't until the Biochemistry paper that all the pieces were put together.  

All of a sudden (semi-empirical) electronic structure theory could be used to say something meaningful about a system with a thousand atoms (1650 to be exact).  Specifically that Lys12 is most important to catalysis and His95 could act as an acid/base catalyst.

Despite being the first of its kind, the paper still reads very much like a "modern" study and I think it is fair to say that most subsequent QM/MM studies of enzymes are really variations on the themes introduced in this paper.

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How to Make the sigma0pi2 Singlet the Ground State of Carbenes

Chen, B.; Rogachev, A. Y.; Hrovat, D. A.; Hoffmann, R.; Borden, W. T.  J. Am. Chem. Soc. 2013, 135, 13954
Contributed by Steven Bachrach.
Reposted from Computational Organic Chemistry with permission

The singlet and triplet carbene is the topic of Chapter 4, especially sections 1 and 2. The ground state of methylene is the triplet, with one electron in the σ-orbital and one electron in the π-orbital, with the spins aligned. The lowest singlet state places the pair of electrons in the σ-orbital, and this state is about 9 kcal mol^-1 higher in energy than the triplet. The next lowest singlet state has one electron in each of the σ- and π-orbitals, with the spins aligned. The singlet state with both electrons in the π-orbital is the highest of these four states, some 60 kcal mol^-1 above the ground state triplet.

Hoffmann and Borden now pose the question “Can the doubly occupied π carbene (¹A₁-σ⁰π²) be the ground state with appropriate substitution?” The answer they find is yes!¹

The trick is to find a combination of substituents that will raise the energy of the σ-orbital and lower the energy of the π-orbital. The latter effect can be enhanced if the π-orbital can be a part of an aromatic (6e^-) ring.

Two of the best possibilities for identifying a ground state ¹A₁-σ⁰π² carbene are 1 and 2. The CASSCF/6-31G(d) optimized geometries of these two are shown in Figure 1. In 1, the nitrogen lone pairs act to destabilize the σ-orbital, while the aldehyde group acts as a withdrawing group to stabilize the π-orbital. The result is that the ¹A₁-σ⁰π⁶ state of 1 is predicted to be about 8 kcal mol^-1 more stable than the triplet state, as per CASPT2 and CCSD(T) computations.

1

2

An ever greater effect is predicted for 2. Here the nitrogen lone pairs adjacent to the carbene act to destabilize the σ-orbital. The empty π-orbital on B lowers the energy of the carbene π-orbital by making it part of the 6-electron aromatic ring. The ¹A₁-σ⁰π⁶ state of 2 is predicted to be about 25 kcal mol^-1 more stable than its triplet state!

1

2

Figure 1. CASSCF/6-31G(d) optimized geometries of the ¹A₁-σ⁰π⁶ states of 1 and 2.

References

(1) Chen, B.; Rogachev, A. Y.; Hrovat, D. A.; Hoffmann, R.; Borden, W. T. "How to
Make the σ⁰π² Singlet the Ground State of Carbenes," J. Am. Chem. Soc. 2013, 135, 13954-13964, DOI:10.1021/ja407116e.

InChIs

1: InChI=1S/C5H2N2O2/c8-1-4-5(2-9)7-3-6-4/h1-2H
InChIKey=QDSVROXEBBWIOO-UHFFFAOYSA-N

2: InChI=1S/C3H3BN2/c1-4-2-6-3-5-1/h1-2,4H
InChIKey=MQJXDZBYOSOLST-UHFFFAOYSA-N

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