# On Integral INICS Aromaticity of Pyridodiazepine Constitutional Isomers and Tautomers

^{1}

^{2}

^{*}

## Abstract

**:**

_{ZZ}indices and can be aromatic only if they are not protonated at the N-atom. All protonated pyrido and seven-membered rings exhibit meaningful positive INICS

_{ZZ}values and can be assigned as antiaromatic. However, some non-protonated pyrido rings also have substantial positive INICS

_{ZZ}indices and are antiaromatic. A weak linear correlation (R

^{2}= 0.72) between the INICS

_{ZZ}values of the pyridine I(6) and diazepine I(7) rings exists and is a consequence of the communication between the π-electron systems of the two rings. The juxtaposition of the INICS descriptor of the six- and seven-membered rings and diverse electron density parameters at the Ring Critical Points (RCP) revealed good correlations only with the Electrostatic Potentials from the electrons and nuclei (ESPe and ESPn). The relationships with other RCP parameters like electron density and its Laplacian, total energy, and the Hamiltonian form of kinetic energy density were split into two parts: one nearly constant for the six-membered rings and one linearly correlating for the seven-membered rings. Thus, most of the electron density parameters at the RCP of the six-membered rings of pyridodiazepines practically do not change with the diazepine type and the labile proton position. In contrast, those of the seven-membered rings display aromaticity changes in the antiaromatic diazepine with its ring structural modifications.

## 1. Introduction

_{ZZ}[38], and NICS

_{πZZ}[39]. For a decade, the NICS scan showing diamagnetic and paramagnetic ring currents has been used [40]. Nevertheless, in 2019, Stanger suggested that the integrated value of NICSπ

_{ZZ}, ∫ NICSπ

_{ZZ}, is also worth looking at [41]. Moreover, as Berger et al. showed in 2022, the NICS integral parameter has a physical justification related to the ring current via Ampère-Maxwell’s law [42]. They found that on this basis, the integration scheme combined with the stagnation graph analysis makes it possible to automatically calculate the current in individual rings and all the vortices present in the molecule [42]. A more advanced use of the law was also published in Ref. [43]. Following Stanger’s idea, in 2022, we studied the behavior of the integral NICS index, INICS, to evaluate the aromaticity of aromatic amino acids [44]. We found that INICS is the most robust and indicative index out of several other NICS indices taken at a particular point of the NICS scan, such as 0, 1, and the curve extrema. The calculations of newly defined indices were made possible thanks to the ARONICS program written in our group [45].

## 2. Results and Discussion

#### 2.1. Energetics

_{DI}); (ii) pyridine–diazepine rings’ condensation (PDC, ΔG

_{PDC}); and (iii) tautomers, (T, ΔG

_{T}). In the former, structures with different N-atom positions in the diazepine ring are compared (m = 1, n = 2–5; m = 2, n = 3,4); in the following, structures with different N-atom positions in the pyridine ring are compared, while the latter structures with different positions of the labile H-atom are compared. To establish ΔG

_{DI}, the most stable tautomers of the most stable condensation types are compared, while to establish ΔG

_{PDC}, the most stable tautomers are compared (Table 1 and Table 2).

#### 2.1.1. [m,n]diazepine Isomers

#### 2.1.2. Pyridine–Diazepine Rings Condensation

#### 2.1.3. Tautomers

#### 2.2. Integral INICS Aromaticity

_{ZZ}scan, it is immediately seen that the pyridine rings in the N1-H and N3-H tautomers are aromatic: the curves are directed to negative values (Figure 1a and Figure S2). In contrast, after location of the labile H-atom in the N9 position, the ring becomes strongly antiaromatic with the NICS scan directed toward positive values (Figure 1a). On the other hand, irrespectively the tautomer type, the NICS-curves of the [1,3]diazepine ring are directed towards positive values which mean that these rings are antiaromatic (Figure 1b). A closer look into the INICS values shows that for the pyridine ring and N1-H and N3-H tautomers, they are very close, −74.8 and −73.0 ppm·Å, while for the N9-H tautomer, it equals 278.3 ppm·Å. In contrast, for the [1,3]diazepine ring, the INICS values are equal to 102.5, 128.1, and 114.4 ppm·Å for the N1-H, N3-H, and N9-H tautomer, respectively.

_{ZZ}= −75.6 ppm·Å and the NICS

_{ZZ}plot has only negative values. On the other hand, the INICS

_{ZZ}values for the N2-H and N6-H tautomers are 173.3 and 146.7 ppm·Å, respectively, and the curves go only through the positive values, indicating the ring antiaromaticity (Figure S1). Notice that atypically, the diazepine ring in the more stable N2-H tautomer is flat. The diazepine rings in all pyrido[1,2]diazepines are antiaromatic regardless of the type of tautomer and the type of condensation. For the [1,2]diazepine ring, the most considerable positive value of 580.5 ppm·Å is for the planar N2-H tautomer, and the intermediate for the N9-H tautomer is 287.5 ppm·Å, while the lowest value is 92.1 ppm·Å for the N1-H one. Considering the N9 condensation type, the sum of the INICS

_{ZZ}values of the two rings agree qualitatively with the stability order: 16.5, 434.1, and 753.8 ppm·Å (Table 3) vs. 0.00, 27.70, and 19.34 kcal/mol (Table 1).

_{ZZ}= −55 ÷ 78 ppm·Å, Table 3). Thus, the pyridine ring in the remaining two N4-H and N6-H tautomers is antiaromatic (INICS

_{ZZ}= 71.4 and 170.3 ppm·Å, respectively; Figure S3). For all tautomers and condensation types, the NICS

_{ZZ}scan curves for the diazepine rings are positive, and they are antiaromatic. For the N9 condensation type, the INICSZZ([1,4]diazepine ring) = 136.6, 221.7, and 320.9 ppm·Å for the N1-H, N4-H, and N9-H tautomer, respectively. Unlike the [1,3] and [1,2] pyrido-diazepines, the agreement between the stability order and the sum of the INICS values occurs only for the N7 condensation type (Table 1 and Table 3). However, the lowest sum of the INICS always corresponds to the most stable tautomer of the given condensation type.

_{ZZ}scans for the pyridine ring go through the positive values, and INICS

_{ZZ}equals 133 and 144 ppm·Å, respectively (Table 3, Figure S4). The diazepine rings exhibit positive INICS

_{ZZ}values for all tautomers, clearly indicating its antiaromaticity. The most stable N1-H(N5-H) tautomer for N9(N6) condensation has INICS

_{ZZ}values equal to −60.3 ppm and 153.2 ppm·Å for pyridine and diazepine rings, respectively. The energetic stability order of the pyrido[1,5]diazepine tautomers is not reflected in the sums of the INICS

_{ZZ}values, but the least stable isomer always has the highest INICS

_{ZZ}value.

_{zz}-scans for pirydo [2,3]diazepines show that in the case of N6 and N7 condensations, the pyridine ring is aromatic only for the N3-H tautomers (Figure S5). For the remaining tautomers and condensation types, the NICSzz scans of the pyridine and diazepine rings go only through the positive NICS

_{ZZ}values. Although the INICS

_{ZZ}values do not follow the stability order, it is worth noting that for the most stable N3-H tautomer and N6 condensation type and the second stable N3-H tautomer and N7 condensation type, the sums of the INICS

_{ZZ}values of two rings are the lowest: 142 and 177 ppm·Å, respectively (Table 3).

_{zz}scans go through the positive values, and all INICS

_{ZZ}sum values are higher than 400 ppm·Å, showing that the rings are not aromatic (Figure S6). Interestingly, for each condensation type, the sum of the INICS

_{ZZ}values agree qualitatively with the stability order (Table 2 and Table 3).

_{ZZ}values of the pyridine rings or, more often, the INICS

_{ZZ}sum of both the six-member and seven-member rings. For this reason, we tested whether there is a general relationship between INICS

_{ZZ}values and pyrido[m,n]diazepine stability. However, a comparison of the relative values of the molecular energies related to the energy of the most stable isomer, i.e., the N1-H N9 tautomer of condensed pyrido[1,3]diazepine (see total energies, Table S1), showed that no such general trend exists. Indeed, the square of the regression coefficient of the linear correlations between the relative energies and the INICS

_{ZZ}values of pyridine, diazepine, and the sum of the two values is 0.45, 0.23, and 0.33, respectively. Nevertheless, there exists a weak linear correlation (R

^{2}= 0.72) between the INICS

_{ZZ}values of the pyridine I(6) and diazepine I(7) rings (Figure 2). This correlation is a consequence of the communication between the π-electron systems of the two rings. However, it is often hindered by the presence of single bonds around the Nk-H moiety in the diverse tautomers of pyrido[n,m]diazepines, which disrupts the continuity of the π-electron system and, therefore, weakens the correlation.

_{SUM}= I(R6) + I(R7) for a supporting description of the aromaticity of the entire system. Still, we know that it cannot be taken as a rigorous measure of the ring current through the rim of a condensed two-ring system because this index silently assumes the additive contribution of the two rings. Yet, the problem of estimating the index for the rim over two rings is complex. If it could be easy, the solution would already be given in the Berger et al. paper [42], demonstrating physical justification for the NICS integral parameter based on Ampère–Maxwell’s law. However, in the article, only planar and symmetrical (convex) rings have been considered: cyclobutadiene, benzene, cyclohexadiene, borazine, para-benzoquinone, hexadehydro annulene, and central rings of porphyrin and isophlorin.

#### 2.3. INICS vs. Electron Density Parameters at the Ring Critical Points

## 3. Methods

^{2}≥ 0.997 for energies and ≥0.92 for aromaticity indices. However, the correlations are the best for INICS (R

^{2}= 0.989) and the least good for NICS(0) (R

^{2}= 0.920). The high quality of the correlations makes a separate discussion of the solvent effect unnecessary. Ultimately, we performed the reference DFT calculations as the most popular, and the routinely used semi-empirical global hybrid B3LYP functional has several known drawbacks [94,95]. We calculated all systems with a long-range-corrected CAM-B3LYP functional [96,97] and BHandHlyp (Becke-Half-and-Half-LYP) functional with a 1:1 mixture of DFT and exact exchange, which performs well in several medium sized organic systems [98,99]. Eventually, we achieved satisfactory agreement between the results found using all three functionals (Figure S1). In particular, the energy differences between tautomers predicted using the B3LYP functional agreed with those of the two others. Therefore, we can state that conclusions derived based on the B3LYP functional are semi-quantitatively valid for a larger group of hybrid functionals.

## 4. Conclusions

_{ZZ}scans, the six-membered pyrido rings have negative INICS

_{ZZ}values and can be aromatic only if not protonated at the N-atom. All protonated pyrido rings exhibit meaningful positive INICS

_{ZZ}values and can be assigned as antiaromatic. However, some non-protonated pyrido rings also have substantial positive INICS

_{ZZ}indices and are antiaromatic. This is the case of the tautomers of pyrido[1,2]diazepine and pyrido[1,4]diazepine other than the N1-H ones, all pyrido[2,4]diazepine isomers, and all but two pyrido[2,3]diazepine isomers. All seven-membered rings in the studied molecules have large positive INICS

_{ZZ}values and thus can be described as antiaromatic. The comparison of the INICS values for the six- and seven-membered rings reveals a weak linear correlation (R

^{2}= 0.72), displaying communication between the π-electron systems of the two rings.

## Supplementary Materials

## Author Contributions

## Funding

## Institutional Review Board Statement

## Informed Consent Statement

## Data Availability Statement

## Acknowledgments

## Conflicts of Interest

## Sample Availability

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**Scheme 1.**Various condensations of pyridine (

**a**) and [n,m]diazepine (

**b**) rings through the C10–C11 junction bond to form pyridino[m,n] benzodiazepine. The structures are hydrogen depleted. The condensation causes a redistribution of the electron charge.

**Scheme 2.**Example of tautomeric equilibria between the N1-H, N2-H, and N9-H tautomers of the pyrido[1,2]diazepines.

**Scheme 3.**The most stable forms of pyrido[m,n]diazepines for given m and n positions of the N-atoms. The energy differences are given as ΔG

_{DI}(kcal/mol).

**Figure 1.**The NICSzz−scans vs. distance from the ring center along normal to the ring for the most stable pirydo[1,3]diazepines for N9 condensation type. Scans (

**a**) refer to the pyridine, whereas (

**b**) to the [1,3]diazepine ring. Bq stands for the point in which NICSZZ was determined.

**Scheme 4.**The stability of pyridine–diazepine condensation in the pyrido[1,n]diazepine isomers (n = 2, 3, 4) decreases from left to right. For given n, in the most stable isomers, the labile H-atom is always positioned at the N1-atom. One of the X1, X2, and X3-atoms is N, while the others are C. See text for [1,5]- and [2,n]-isomers.

**Figure 2.**Linear trend between INICS

_{ZZ}values of the 6− and 7−membered rings in pyrido[m,n]diazepines I(6) and I(7) (ppm·Å), respectively. [m,n] = [1,2], 1,3], [1,4], [1,5], and [2,3]. The values for pyrido[2,4]diazepines form a separate trend and were omitted. The k(h) notation stands for the Nk condensation type and Nh-H tautomer of the most stable pyrido[1,3]diazepine.

**Figure 3.**Linear correlations between Electrostatic Potential in Ring Critical Points NICS aromaticity indices INICS, NICS(1), and NICS(0) of the 6− and 7−membered rings in pyrido[m,n]diazepines and (

**a**) ESPe (Electrostatic Potential from Electrons), and (

**b**) ESPn (Electrostatic Potential from Nuclei).

**Figure 4.**Linear correlations between the electron density and Laplacian of electron density in Ring Critical Points and INICS aromaticity index of the 7−membered rings in pyrido[m,n]diazepines and lack of such a correlation for the 6−membered rings: (

**a**) electron density Rho, and (

**b**) Laplacian of electron density ∇

^{2}(Rho). Two points of [2,3]− and two of [2,4]−isomers deviate from trends and are omitted.

**Figure 5.**Linear correlations between energies in Ring Critical Points and INICS aromaticity index of the 7−membered rings in pyrido[m,n]diazepines and lack of such a correlation for the 6−membered rings: (

**a**) Total Energy H (H = G + V), and (

**b**) Hamiltonian Form of Kinetic Energy Density K. Two points of [2,3]− and two of [2,4]−isomers deviate from trends and are omitted.

**Table 1.**The energy differences and relative Gibbs free energies ΔG

_{PDZ}, ΔG

_{T}, ΔE

_{PC}, ΔG

_{PC}(kcal/mol) are referred to, respectively, by the most stable isomer of pyrido[1,n]diazepines n = 2,3,4,5 pyridine condensation (PC) in a given diazepine type (DT), tautomer type (T) in particular types of pyridine condensation, and planarity (P) bicyclic system of np (non-planar) and p and (planar) tautomers.

PC | T | P | ΔG_{PDZ} | ΔG_{PC} | ΔE_{T} | ΔG_{T} | PC | T | P | ΔG_{PDZ} | ΔG_{PC} | ΔE_{T} | ΔG_{T} | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

pyrido[1,2]diazepines | N6 | N1-H | n | 4.89 | 0.00 | 0.00 | pirydo[1,4]diazepinese | N6 | N1-H | n | 6.63 | 0.00 | 0.00 | ||

N2-H | n | 19.64 | 19.03 | N4-H | n | 19.98 | 19.40 | ||||||||

N2-H | p | 22.09 | 21.38 | N6-H | n | 18.63 | 17.16 | ||||||||

N6-H | n | 36.20 | 34.53 | N7 | N1-H | n | 5.00 | 0.00 | 0.00 | ||||||

N7 | N1-H | n | 4.22 | 0.00 | 0.00 | N4-H | p | 20.39 | 19.51 | ||||||

N2-H | n | 18.89 | 18.63 | N4-H | n | 20.20 | 19.51 | ||||||||

N7-H | n | 22.44 | 21.33 | N7-H | n | 15.05 | 14.37 | ||||||||

N8 | N1-H | n | 6.17 | 0.00 | 0.00 | N8 | N1-H | n | 7.45 | 0.00 | 0.00 | ||||

N2-H | p | 19.69 | 19.15 | N4-H | n | 22.86 | 22.04 | ||||||||

N2-H | n | 23.56 | 22.69 | N8-H | p | 19.06 | 17.37 | ||||||||

N8-H | n | 27.69 | 26.39 | ||||||||||||

N9 | N1-H | n | 19.74 | 0.00 | 0.00 | 0.00 | N9 | N1-H | n | 7.13 | 0.00 | 0.00 | 0.00 | ||

N2-H | p | 25.61 | 24.75 | N4-H | n | 27.60 | 26.63 | ||||||||

N2-H | n | 28.71 | 27.78 | N9-H | p | 13.03 | 12.02 | ||||||||

N9-H | n | 21.08 | 19.34 | ||||||||||||

pyrido [1,3]diazepines | N6 | N1-H | n | 2.06 | 2.37 | pirydo [1,5]diazepines | N6 | N1-H | n | 8.06 | 7.73 | ||||

N3-H | n | 3.86 | 0.00 | 0.00 | N5-H | n | 4.54 | 0.00 | 0.00 | 0.00 | |||||

N6-H | n | 16.70 | 16.16 | N6-H | p | 11.65 | 10.82 | ||||||||

N7 | N1-H | n | 0.52 | 1.84 | N7 | N1-H | n | 5.92 | 0.00 | 0.00 | |||||

N3-H | n | 3.62 | 0.00 | 0.00 | N5-H | n | 0.58 | 0.66 | |||||||

N7-H | n | 16.49 | 16.90 | N7-H | p | 13.18 | 12.12 | ||||||||

N8 | N1-H | n | 1.07 | 1.75 | N8 | N1-H | p | 0.58 | 0.66 | ||||||

N3-H | n | 4.83 | 0.00 | 0.00 | N5-H | n | 5.92 | 0.00 | 0.00 | ||||||

N8-H | n | 17.96 | 17.85 | N8-H | p | 13.18 | 12.12 | ||||||||

N9 | N1-H | n | 0.00 | 0.00 | 0.00 | 0.00 | N9 | N1-H | n | 0.00 | 0.00 | 0.00 | |||

N3-H | n | 6.10 | 5.63 | N5-H | n | 8.06 | 7.73 | ||||||||

N9-H | n | 12.64 | 11.95 | N9-H | n | 11.65 | 10.82 |

**Table 2.**The energy differences and relative Gibbs free energies ΔG

_{PDZ}, ΔG

_{T}, ΔE

_{PC}, ΔG

_{PC}(kcal/mol) are referred to, respectively, by the most stable isomer of pyrido[2,n]diazepines n = 3, 4, pyridine condensation (PC) in a given diazepine type (DT), tautomer type (T) in particular types of pyridine condensation, and planarity (P) bicyclic system of np (non-planar) and p and (planar) tautomers.

PC | T | P | ΔG_{PDZ} | ΔG_{PC} | ΔE_{T} | ΔG_{T} | PC | T | P | ΔG_{PDZ} | ΔG_{PC} | ΔE_{T} | ΔG_{T} | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

pyrido[2,3]diazepines | N6 | N2-H | p | 18.64 | 18.63 | pirydo[2,4]diazepinese | N6 | N2-H | p | 5.58 | 5.42 | ||||

N3-H | n | 22.81 | 0.00 | 0.00 | 0.00 | N4-H | n | 3.97 | 4.24 | ||||||

N6-H | n | 21.90 | 21.15 | N6-H | p | 26.16 | 0.00 | 0.00 | 0.00 | ||||||

N7 | N2-H | p | 18.22 | 18.47 | N7 | N2-H | p | 4.77 | 4.75 | ||||||

N3-H | n | 1.77 | 0.00 | 0.00 | N4-H | p | 6.26 | 6.32 | |||||||

N7-H | n | 30.11 | 28.89 | N7-H | n | 0.05 | 0.00 | 0.00 | |||||||

N8 | N2-H | n | 18.23 | 0.00 | 0.00 | N8 | N2-H | p | 6.26 | 6.32 | |||||

N3-H | p | 1.93 | 2.01 | N4-H | p | 4.77 | 4.75 | ||||||||

N8-H | n | 4.57 | 3.76 | N8-H | n | 0.05 | 0.00 | 0.00 | |||||||

N9 | N2-H | n | 17.89 | 0.00 | 0.00 | N9 | N2-H | n | 3.97 | 4.24 | |||||

N3-H | p | 0.83 | 0.74 | N4-H | p | 5.58 | 5.42 | ||||||||

N9-H | p | 11.38 | 9.71 | N9-H | p | 26.16 | 0.00 | 0.00 | 0.00 |

**Table 3.**The INICS values of pyrido[m,n]diazepines m = 1, 2; n = 2, 3, 4, 5; m ≠ n, pyridine for pyridine (R6) and diazepine (R7) rings. Only the most stable form of a given tautomer is taken into account.

PC | T | I(R6) | I(R7) | I_{SUM} | PC | T | I(R6) | I(R7) | I_{SUM} | PC | T | I(R6) | I(R7) | I_{SUM} | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

pyrido[1,2]diazepines | N6 | N1-H | −95.9 | 64.5 | −31.4 | pyrido[1,3]diazepines | N6 | N1-H | −85.0 | 94. 6 | 9.5 | pyrido[1,4]diazepines | N6 | N1-H | −77.5 | 118.0 | 40.4 |

N2-H | 158.8 | 588.8 | 747.6 | N3-H | −50.9 | 176.8 | 125.9 | N4-H | 73.4 | 255.0 | 328.4 | ||||||

N6-H | 171.5 | 329.4 | 501.0 | N6-H | 120.8 | 280.9 | 401.8 | N6-H | 243.2 | 431.0 | 674.2 | ||||||

N7 | N1-H | −81.7 | 90.1 | 8.3 | N7 | N1-H | −78.4 | 107.6 | 29.1 | N7 | N1-H | −57.7 | 147.8 | 90.2 | |||

N2-H | 168.6 | 569.4 | 738.0 | N3-H | −31.4 | 214.0 | 182.5 | N4-H | 128.8 | 371.9 | 500.8 | ||||||

N7-H | 74.7 | 163.5 | 238.2 | N7-H | 106.0 | 265.1 | 371.1 | N7-H | 122.6 | 246.4 | 369.0 | ||||||

N8 | N1-H | −96.0 | 70.5 | −25.5 | N8 | N1-H | −85.3 | 99.0 | 13.7 | N8 | N1-H | −77.3 | 125.3 | 48.0 | |||

N2-H | 170.2 | 604.5 | 774.6 | N3-H | −38.3 | 204.0 | 165.7 | N4-H | 65.0 | 236.1 | 301.1 | ||||||

N8-H | 75.7 | 128.2 | 203.8 | N8-H | 129.1 | 293.0 | 422.2 | N8-H | 278.3 | 514.2 | 792.5 | ||||||

N9 | N1-H | −75.6 | 92.1 | 16.5 | N9 | N1-H | −74.8 | 102.5 | 27.7 | N9 | N1-H | −55.0 | 136.6 | 81.6 | |||

N2-H | 173.3 | 580.5 | 753.8 | N3-H | −73.0 | 128.1 | 55.2 | N4-H | 71.4 | 221.7 | 293.1 | ||||||

N9-H | 146.7 | 287.5 | 434.1 | N9-H | 278.3 | 114.4 | 392.7 | N9-H | 170.3 | 320.9 | 491.2 | ||||||

pyrido[1,5]diazepines | N6 | N1-H | −84.5 | 114.1 | 29.7 | pyrido[2,3]diazepines | N6 | N2-H | 186.9 | 554.0 | 740.9 | pyrido[2,4]diazepines | N2-H | 808.0 | 325.1 | 1133.0 | |

N5-H | −60.3 | 153.2 | 92.9 | N3-H | −38.9 | 181.2 | 142.3 | N6 | N4-H | 651.9 | 246.4 | 898.3 | |||||

N6-H | 133.1 | 343.9 | 477.0 | N6-H | 91.0 | 127.9 | 218.9 | N6-H | 278.7 | 230.5 | 509.2 | ||||||

N7 | N1-H | −60.0 | 167.0 | 107.0 | N7 | N2-H | 168.4 | 549.5 | 717.9 | N2-H | 820.6 | 331.3 | 1151.8 | ||||

N5-H | −72.9 | 146.1 | 73.2 | N3-H | −32.8 | 210.2 | 177.4 | N7 | N4-H | 913.7 | 383.9 | 1297.6 | |||||

N7-H | 144.4 | 373.5 | 518.0 | N7-H | 191.8 | 327.3 | 519.2 | N7-H | 252.1 | 187.4 | 439.4 | ||||||

N8 | N1-H | −72.9 | 146.1 | 73.2 | N8 | N2-H | 198.2 | 582.1 | 780.3 | N2-H | 913.7 | 383.9 | 1297.6 | ||||

N5-H | −60.0 | 167.0 | 107.0 | N3-H | 168.4 | 549.5 | 717.9 | N8 | N4-H | 820.6 | 331.3 | 1151.8 | |||||

N8-H | 144.4 | 373.5 | 518.0 | N8-H | 77.0 | 118.8 | 195.8 | N8-H | 252.1 | 187.4 | 439.4 | ||||||

N9 | N1-H | −60.3 | 153.2 | 92.9 | N9 | N2-H | 165.6 | 543.7 | 709.4 | N2-H | 651.9 | 246.4 | 898.3 | ||||

N5-H | −84.5 | 114.1 | 29.7 | N3-H | 186.9 | 186.9 | 373.9 | N9 | N4-H | 807.9 | 325.2 | 1133.1 | |||||

N9-H | 133.1 | 343.9 | 477.0 | N9-H | 240.5 | 392.9 | 633.4 | N9-H | 278.7 | 230.5 | 509.2 |

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**MDPI and ACS Style**

Jarończyk, M.; Ostrowski, S.; Dobrowolski, J.C.
On Integral INICS Aromaticity of Pyridodiazepine Constitutional Isomers and Tautomers. *Molecules* **2023**, *28*, 5684.
https://doi.org/10.3390/molecules28155684

**AMA Style**

Jarończyk M, Ostrowski S, Dobrowolski JC.
On Integral INICS Aromaticity of Pyridodiazepine Constitutional Isomers and Tautomers. *Molecules*. 2023; 28(15):5684.
https://doi.org/10.3390/molecules28155684

**Chicago/Turabian Style**

Jarończyk, Małgorzata, Sławomir Ostrowski, and Jan Cz. Dobrowolski.
2023. "On Integral INICS Aromaticity of Pyridodiazepine Constitutional Isomers and Tautomers" *Molecules* 28, no. 15: 5684.
https://doi.org/10.3390/molecules28155684