Next Article in Journal
Research on Hydrogen Production from Ammonia Decomposition by Pulsed Plasma Catalysis
Previous Article in Journal
Ni-Mg-Al Hydrotalcite-Derived Catalysts for Ammonia Decomposition—From Precursor to Effective Catalyst
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 30
Issue 5
10.3390/molecules30051053
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Thermodynamic Cards of Classic NADH Models and Their Related Photoexcited States Releasing Hydrides in Nine Elementary Steps and Their Applications

by
Bao-Chen Qian
1,
Xiao-Qing Zhu
2,* and
Guang-Bin Shen
1,*
1
College of Medical Engineering, Jining Medical University, Jining 272000, China
2
Department of Chemistry, Nankai University, Tianjin 300071, China
*
Authors to whom correspondence should be addressed.
Molecules 2025, 30(5), 1053; https://doi.org/10.3390/molecules30051053
Submission received: 11 February 2025 / Revised: 22 February 2025 / Accepted: 24 February 2025 / Published: 25 February 2025
(This article belongs to the Section Organic Chemistry)
Browse Figures
Versions Notes

Abstract

Thermodynamic cards of three classic NADH models (XH), namely 1-benzyl-1,4-dihydronicotinamide (BNAH), Hantzsch ester (HEH), and 10-methyl-9,10-dihydroacridine (AcrH), as well as their photoexcited states (XH*: BNAH*, HEH*, AcrH*) releasing hydrides in nine elementary steps in acetonitrile are established. According to these thermodynamic cards, the thermodynamic reducing abilities of XH* are remarkably enhanced upon photoexcitation, rendering them thermodynamically highly potent electron, hydrogen atom, and hydride donors. The application of these thermodynamic cards to imine reduction is demonstrated in detail, revealing that photoexcitation enables XH* to act as better hydride donors, transforming the hydride transfer process from thermodynamically unfeasible to feasible. Most intriguingly, AcrH* is identified as the most thermodynamically favorable electron, hydride, and hydrogen atom donor among the three classic NADH models and their photoexcited states. The exceptional thermodynamic properties of XH* in hydride release inspire further investigation into the excited wavelengths, excited potentials, and excited state stabilities of more organic hydrides, as well as the discovery of novel and highly effective photoexcited organic hydride reductants.

Graphical Abstract

1. Introduction

Nicotinamide coenzyme is a vital oxidoreductase in vivo, participating in numerous essential enzymatic reactions as a hydride carrier [1,2]. Many organic hydrides (XH) were designed and synthesized as NADH models to mimic the outstanding reducing properties of NADH coenzyme in vitro [3]. Among them, 1-benzyl-1,4-dihydronicotinamide (BNAH), Hantzsch ester (HEH), and 10-methyl-9,10-dihydroacridine (AcrH) are the most classic NADH models, featuring a typical 1,4-dihydropyridine structure (Scheme 1a), whose redox properties have been extensively studied and well established in previous literature [3,4]. Moreover, photoexcited organic hydrides (XH*) have been discovered and verified to exhibit superior reducing activity, characterized by extremely lower oxidation potentials and stronger thermodynamic driving forces for releasing hydrogen atoms or hydrides [5,6,7].
Until now, organic hydrides (XH) [8,9,10] and photoexcited organic hydrides (XH*) [5,6,7], particularly BNAH, AcrH, HEH, and their photoexcited states (BNAH*, AcrH*, and HEH*), are not merely used as hydride or hydrogen molecule (H2) reductants for reducing unsaturated compounds. As hydride carriers, organic hydrides (XH) [8,9,10], especially photoexcited organic hydrides (XH*) [5,6,7], can provide electrons, hydrogen atoms, protons, or hydrides (Scheme 1b) to generate key intermediates such as radical anions, radicals or anions. These intermediates subsequently undergo chemical transformations to construct various molecules with structural complexity. In fact, BNAH, AcrH, and HEH can be easily excited to their photoexcited states (BNAH*, AcrH*, and HEH*) in solution, and have been widely applied into photochemical synthesis [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. Since the process of XH or XH* acting as reducing reagents in chemical reactions may involve multiple mechanisms (Scheme 1b), including e [11,12,13,14,15,16], e + H• [17,18,19,20,21,22,23], e + H+ + e [24,25], H• + e [26], H− [9,10,27,28], and nine possible elementary steps (Scheme 2), the corresponding nine thermodynamic driving forces for XH or XH* releasing hydride are crucial and urgently desired thermodynamic parameters to enable chemists to predict and evaluate the characteristic properties of various reaction intermediates [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28] and elucidate the reaction mechanisms.
Our group has been committed to determining the thermodynamic data associated with the release of hydrides from organic hydrides in acetonitrile [3]. In our previous work, the six possible thermodynamic driving forces of BNAH, HEH and AcrH releasing hydrides in acetonitrile were experimentally determined in a lab [3,4]. Given the vital applications of BNAH*, HEH* and AcrH* into photochemical synthesis as hydride carriers [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27], herein, the thermodynamic cards for the three classic NADH models, i.e., BNAH, HEH and AcrH, as well as their related excited states (BNAH*, HEH* and AcrH*) releasing hydrides (Scheme 2) are established, aiming to elucidate and understand the reducing abilities of XH, XH* and related intermediates, and to further demonstrate their applications in reduction reactions.

2. Results and Discussion

2.1. The Definitions, and Sources of Nine Potential Thermodynamic Driving Forces for XH and XH* Releasing Hydrides in Acetonitrile

For XH and XH*, there are a total of nine possible elementary steps (Steps 1–9) involving in the release of hydrides, which are clearly illustrated in Scheme 2.
Specifically, Step 1 and Step 4 in Scheme 2 represent the chemical processes of XH and X• releasing electrons, described by the equations XH → XH•+ + e and X• → X+ + e, respectively. The thermodynamic driving forces of Step 1 and Step 4 are defined as the oxidation potentials of XH and X•, denoted as Eox(XH) and Eox(X•), which are determined by electrochemical experiments in a lab.
However, due to the highly unstable nature of X• in solution, direct measurement of Eox(X•) is not feasible. Additionally, the reduction potentials of X+ and oxidation potentials of XH are irreversible in acetonitrile. Therefore, the potential determinations were performed using a combination of Cyclic Voltammetry (CV) and Osteryoung Square Wave Voltammetry (OSWV) methods simultaneously via an electrochemical apparatus (BAS-100B) under an inert atmosphere of Ar or N2 in deaerated acetonitrile to ensure accurate and reliable results [3,4].
Numerous studies have confirmed that the OSWV method is a more precise electrochemical technique for evaluating the single-electron redox potentials of substrates with irreversible electrochemical processes compared with the CV method, with uncertainties potentially as low as a few tenths of a millivolt [29,30]. Accordingly, the oxidation potential of X• is equivalent to the reduction potential of X+, Eox(X•) = Ered(X+), and the Ered(X+) can be easily and directly determined using the OSWV method.3–4 In this context, the standard oxidation potential values of XH and X•, Eox(XH) and Eox(X•) in acetonitrile were derived from our previous electrochemical experiment using the OSWV method [3,4]. Utilizing the OSWV method, the single-electron redox capabilities of 421 organic hydrides and unsaturated compounds were measured and evaluated in acetonitrile [3]. Based on their redox potentials and hydricities, thermodynamic cards for these 421 organic hydrides and unsaturated compounds were established, detailing their abilities to release or accept hydrides. These thermodynamic cards have been successfully applied to reduction reactions, providing valuable insights into their reactivity and potential applications [3].
Step 2 in Scheme 2 is the chemical process of XH releasing hydrides, described by the equation XH → X+ + H−. The thermodynamic driving force of Step 2 is described as the molar enthalpy change of XH releasing hydrides, denoted as ΔHH−R(XH) (where the subscripted “H−R” refers to hydrides release throughout the text). ΔHH−R(XH) values were obtained by determining the molar reaction heat (ΔHr) between XH and hydride acceptor (Y+), whose molar enthalpy change of Y+ accepting hydrides ΔHH−A(Y+) is well established and determined using isothermal titration calorimeter (ITC) in acetonitrile. The molar reaction heat (ΔHr) is defined as the molar enthalpy change of the hydride transfer reaction from one molar equivalent of hydride donor (XH) to one molar equivalent of hydride acceptor (Y+). ΔHH−R(XH) can be calculated by the following Equation (1), ΔHH−R(XH) = ΔHH−A(Y+) + ΔHr (Equation (1)) [3,4]. Equation (1) allows us to determine the thermodynamic driving force for the release of hydrides from XH, which is a critical parameter for understanding the reducing abilities of XH and its potential applications in reduction reactions.
Step 3 in Scheme 2 is the chemical process of XH releasing hydrogen atoms, XH → X• + H•, and the thermodynamic driving force of Step 2 is described as the molar enthalpy change of XH releasing hydrogen atoms, ΔHHR(XH), which is derived from Equation (2), ΔHHR(XH) = ΔHH−R(XH) − F[Ered(X+) − Ered(H•)] (Equation (2)), by constructing thermodynamic cycle I (Step 3–Step 4–Step 2) in Scheme 2 [3,29,30]. Among Equation (2), Ered(H•) is reported as 1.128 V vs. Fc in acetonitrile and F is the faraday constant (23.06 kcal/V). It should be pointed out that the subscripted “HR” in ΔHHR refers to hydrogen atoms releasing in the whole text.
Step 5 in Scheme 2 is the chemical process of XH•+ releasing hydrogen atoms, described by the equation XH•+ → X+ + H•. The thermodynamic driving force of Step 5 is the molar enthalpy change associated with the release of hydrogen atoms from XH•+, denoted as ΔHHR(XH•+). This value is derived from the following Equation (3), ΔHHR(XH•+) = ΔHH−R(XH) − F[Eox(XH) − Ered(H•)] (Equation (3)), by constructing thermodynamic cycle II [3,29,30] (Step 1–Step 5–Step 2) in Scheme 2.
Step 6 in Scheme 2 represents the chemical process of XH•+ releasing protons, described by the equation XH•+ → X• + H+. The thermodynamic driving force of Step 6 is described as the molar enthalpy change of XH•+ releasing protons, denoted as ΔHPR(XH•+). These values are derived from Equation (4), ΔHPR(XH•+) = ΔHHR(XH) − F[Eox(XH) − Eox(H•)] (Equation (4)). The equation is established by forming the thermodynamic cycle III [3,29,30] (Step 1–Step 6–Step 3) in Scheme 2.
Step 7 in Scheme 2 is the chemical process of XH* releasing electrons, XH* → XH•+ + e. The thermodynamic driving force of Step 7 is described as the oxidation potential of XH*, denoted as Eox(XH*). The oxidation potentials of the related photoexcited states BNAH*, HEH*, and AcrH* have been estimated as −2.98 V [31,32,33], −2.66 V [34], and −3.48 V [35,36] (V vs. Fc) respectively, which are available from published studies. In addition, the lifetimes of BNAH*, AcrH*, and HEH* are reported as 0.76 ns [33], 7 ns [5,35] and 0.32 ns [19], respectively. The Eox(XH*) values were typically obtained by integrating fluorescence or UV-vis with electrochemical technologies [32,37,38]. It should be noted that the potentials are converted from the standard calomel electrode (SCE) to ferrocene (Fc) by subtracting 0.380 V, based on the standard potentials of SCE and Fc in acetonitrile [39].
Step 8 in Scheme 2 is the chemical process of XH* releasing hydrides or electron-coupled hydrogen atoms (ECH), XH* → X+ + H− and XH* → X+ + ECH, and the thermodynamic driving force of Step 8 is described as the molar enthalpy change associated with the release of hydrides or ECH from XH*, denoted as ΔHH−R(XH*). Given that the electron-donating ability of XH* is significantly enhanced upon photoexcitation, ΔHH−R(XH*) can be calculated from ΔHH−R(XH) and Eox(XH*) using Equation (5), ΔHH−R(XH*) = ΔHH−R(XH) − F[Eox(XH) − Eox(XH*)] (Equation (5)), according to Hess’ law.
Step 9 in Scheme 2 is the chemical process of XH* releasing hydrogen atoms or proton-coupled electrons (PCE), XH* → X• + H• and XH* → X• + PCE. The thermodynamic driving force of Step 9 is described as the molar enthalpy change of XH* releasing hydrogen atoms or PCE, ΔHHR(XH*). These values were derived from Equation (6), ΔHHR(XH*) = ΔHH−R(XH*) − F[Ered(X+) − Ered(H•)] (Equation (6)), by constructing thermodynamic cycle IV [3,29,30] (Step 9–Step 4–Step 8) in Scheme 2.
Note that we used Gibbs free energy change ∆Get, ∆Get = F∆E, to replace the enthalpy change ∆Het in Equations (2)–(6) for the electron transfer processes. This substitution is suitable due to the fact that the entropy changes associated with electron transfer are negligible, as verified by Arnett et al. [29,30,40]. In our previous work, employing the same processing strategy, the thermodynamic driving forces for many organic hydrides releasing hydrogen atoms, and organic hydrides radical cations releasing hydrogen atoms or protons were derived by Equations (2)–(4) to characterize the reducing abilities of organic hydrides and related intermediates in acetonitrile [3].

2.2. Establishing Thermodynamic Cards of XH and XH* Releasing Hydrides in Acetonitrile

Herein, the thermodynamic cards in nine potential elementary steps of BNAH, HEH, and AcrH and their related single excited states (BNAH*, HEH*, and AcrH*) releasing hydrides were established and shown in Scheme 3, Scheme 4 and Scheme 5, respectively. Additionally, all the relevant thermodynamic data have been compiled and presented in Table 1 for ease of reference.

2.3. Thermodynamic Abilities of XH* and XH Releasing Electrons

To facilitate a clear comparison of the oxidation potentials of XH and XH* with those of common single electron donors, the Eox(XH) and Eox(XH*) values (vs. Fc), as well as oxidation potentials of common organic hydrides and frequently-used photocatalyst metal complexes are shown in Scheme 6.
As illustrated in Scheme 6, the oxidation potential is 0.219 V for BNAH, 0.479 V for HEH, and 0.460 V for AcrH [3,4]. The thermodynamic electron-releasing abilities decrease in the order of BNAH (0.219 V) > AcrH (0.460 V) > HEH (0.479 V). Upon photoexcitation, the oxidation potentials for the excited states are significantly altered: −2.98 V for BNAH* [31,32,33], −2.66 V for HEH*34 and −3.48 V for AcrH* [35,36]. The order of their thermodynamic electron-donating abilities is substantially changed, with the sequence now being AcrH* (−3.48 V) > BNAH* (−2.98 V) > HEH* (−2.66 V). This indicates that photoexcitation dramatically enhances the electron-donating ability of these compounds, with AcrH* exhibiting the strongest thermodynamic propensity to release electrons among the three.
For the oxidation potentials of XH and XH*, it is observed that the Eox(XH) values of BNAH (0.219 V vs. Fc), HEH (0.479 V vs. Fc), and AcrH (0.460 V vs. Fc) are all greater than 0 V and less than 0.5 V (vs. Fc), 0 < Eox(XH) < 0.5 V. In contrast, the Eox(XH*) values of BNAH* (−2.98 V vs. Fc), HEH* (−2.66 V vs. Fc) and AcrH* (−3.48 V vs. Fc) are significantly more negative than −1.0 V (vs. Fc) and even more negative than that of Eox(H•) (−2.298 V vs. Fc in acetonitrile). This indicates that BNAH, HEH, and AcrH are classified as thermodynamically medium-strong single electron donors [3], whereas their photoexcited counterparts (BNAH*, HEH* and AcrH*) are thermodynamically very strong single electron donors.
When comparing the photoexcited oxidation potentials of BNAH* (−2.98 V vs. Fc), HEH* (−2.66 V vs. Fc) and AcrH* (−3.48 V vs. Fc) with their parents (BNAH, HEH, and AcrH), it is found that the oxidation potential decreases by 3.199 V for BNAH*, 3.139 V for HEH*, and 3.940 V for AcrH*. This suggests that the photoexcitation greatly improves the electron-releasing abilities by at least 72.4 kcal/mol (72.4 kcal/mol for HEH*, 73.8 kcal/mol for BNAH* and 90.9 kcal/mol for AcrH*).
As electron donors, the thermodynamic abilities of XH* and XH to release electrons decrease in the following order of AcrH* (−3.48 V vs. Fc) > BNAH* (−2.98 V vs. Fc) > HEH* (−2.66 V vs. Fc) > BNAH (0.219 V vs. Fc) > AcrH (0.460 V vs. Fc) > HEH (0.479 V vs. Fc). Notably, although the oxidation potentials of HEH (0.479 V vs. Fc) and AcrH (0.460 V vs. Fc) are very close, the electron-releasing ability of AcrH* (80.2 kcal/mol refer to Fc) is 18.9 kcal/mol greater than that of HEH* (61.3 kcal/mol refer to Fc) after photoexcitation.
It is well established that fac-Ir(ppy)3 and RuII(bpy)3 are extensively employed in photocatalytic reactions [41,42,43,44,45], where their key intermediates (IrIII and RuI) serve as highly effective electron donors to activate reaction substrates. If the Eox(XH) and Eox(XH*) values are compared with Eox[IrII(ppy)3] (−2.25 V vs. Fc) and Eox[RuI(bpy)3] (−1.17 V vs. Fc) [46], it is evident that Eox(XH) values (0.219 – 0.479 V vs. Fc) are significantly more positive than that of Eox[RuI(bpy)3] (−1.17 V vs. Fc). Conversely, the Eox(XH*) values (−2.66 – −3.48 V vs. Fc) are much more negative than that of Eox[IrII(ppy)3] (−2.25 V vs. Fc). This comparison indicates that upon photoexcitation, XH* exhibit even stronger thermodynamic single-electron donating abilities than common photocatalysts. Therefore, XH* can serve as superior alternatives to metal-complex photocatalysts [11,12,13,14,15,16], offering the advantage of extremely low oxidation potentials and eliminating the need of additional electron-donating additives.

2.4. Thermodynamic Abilities of XH* and XH Releasing Hydrides

For a more comprehensive comparison, the thermodynamic driving forces associated with the release of hydrides from XH* and related XH, as well as those from common hydride donors, are exhibited in Scheme 7. It is well known that the NADH coenzyme acts as a medium-strong hydride carrier in biological systems, playing an essential role in mediating the transfer of hydrides between substrates and oxidoreductases [1,2,3,4]. Given its structural similarity to NADH, BNAH (64.2 kcal/mol) is considered a thermodynamically medium-strong hydride donor. Similarly, HEH (69.3 kcal/mol) also falls into the category of thermodynamically medium-strong hydride donors [4].
In contrast, AcrH has a significantly weaker thermodynamic ability to release hydrides, being 16.9 kcal/mol less favorable than BNAH (64.2 kcal/mol). As a result, AcrH is recognized as a thermodynamically weak hydride donor. In summary, BNAH (64.2 kcal/mol), HEH (69.3 kcal/mol), and AcrH (81.1 kcal/mol) belong to thermodynamically medium-strong or weak hydride donors individually [3], and the thermodynamic abilities of XH releasing hydrides decrease in the order of BNAH (64.2 kcal/mol, medium-strong) > HEH (69.3 kcal/mol, medium-strong) > AcrH (81.1 kcal/mol, weak).
From Scheme 7, it is clear that the thermodynamic driving force of XH* releasing hydrides is −9.6 kcal/mol for BNAH*, −3.1 kcal/mol for HEH*, −9.8 kcal/mol for AcrH* respectively. The thermodynamic hydride-donating abilities decrease in the following order of AcrH* (−9.8 kcal/mol) ≈ BNAH* (−9.6 kcal/mol) > HEH* (−3.1 kcal/mol). In the published literature, LiAlH4 is reported as a very strong inorganic hydride donor, with a thermodynamic driving force of 47.9 kcal/mol for hydride release [47]. In contrast, the thermodynamic driving forces of XH* releasing hydrides range from −3.1 kcal/mol to −9.8 kcal/mol, which are significantly more negative than that of LiAlH4 (47.9 kcal/mol) [47]. This indicates that XH* are exceptionally strong hydride donors from a thermodynamic standpoint.
Moreover, if the hydride-donating abilities of XH* are compared with free hydride ions (H−, 0.0 kcal/mol), it is found that AcrH* (−9.8 kcal/mol), BNAH* (−9.6 kcal/mol), and HEH* (−3.1 kcal/mol) are even thermodynamically more favorable hydride donors than free hydride ions (H−, 0.0 kcal/mol) in acetonitrile. This remarkable thermodynamic advantage suggests that XH* could serve as highly efficient hydride carriers to activate or reduce challenging substrates in chemical reactions. If the thermodynamic driving forces of XH* (−3.1–−9.8 kcal/mol) releasing hydrides are compared with those of their ground-state parents XH (64.2–81.1 kcal/mol), it is evident that the hydride-donating abilities of XH* are greatly improved by the photoexcitation. As hydride donors, the thermodynamic abilities of XH* and XH releasing hydrides decrease in the order of AcrH* (−9.8 kcal/mol) ≈ BNAH* (−9.6 kcal/mol) > HEH* (−3.1 kcal/mol) > BNAH (64.2 kcal/mol) > HEH (69.3 kcal/mol) > AcrH (81.1 kcal/mol).
As indicated in Scheme 3, Scheme 4 and Scheme 5, an intriguing observation emerges regarding the thermodynamic driving forces associated with the release of electrons from XH*. Specifically, the thermodynamic driving forces of XH* (−2.66 – −3.48 V vs Fc) releasing electrons are greater than −61.3 kcal/mol (referring to Fc, −2.66 V vs. Fc), while the following thermodynamic driving forces of XH•+ (32.0 – 44.2 kcal/mol) releasing hydrogen atoms are smaller than 32.0 kcal/mol. These thermodynamic data strongly suggest that the rate of electron release is likely diffusion-controlled and several orders of magnitude faster than the subsequent hydrogen transfer rate. This disparity in rates clearly indicates that the overall hydride transfer process may proceed via a concerted electron-coupled hydrogen atom (ECH) transfer mechanism in a single step [27]. The thermodynamic analysis of this process mirrors that of XH* releasing hydrides directly, highlighting the significant role of electron coupling in facilitating the hydrogen atom transfer.

2.5. Thermodynamic Abilities of XH* and XH Releasing Hydrogen Atoms

The thermodynamic hydrogen atom-releasing abilities of XH* and related XH, as well as those of common hydrogen atom donors, are presented in Scheme 8. Since ascorbic acid (AscH2) and α-tocopherol (TocOH) are reported as well-known antioxidants in biological systems, the molar enthalpy changes of 5,6-isopropylidene ascorbic acid (iAscH2) and TocOH releasing hydrogen atoms are determined as 75.1 kcal/mol and 79.7 kcal/mol in previous studies in acetonitrile [48], which are shown in Scheme 8 for comparison.
From Scheme 8, it is evident that the thermodynamic driving forces of BNAH (70.9 kcal/mol), HEH (68.7 kcal/mol), and AcrH (73.0 kcal/mol) releasing hydrogen atoms are smaller than that of iAscH2 (75.1 kcal/mol) and TocOH (79.7 kcal/mol) [48]. This implies that BNAH (70.9 kcal/mol), HEH (68.7 kcal/mol), and AcrH (73.0 kcal/mol) are thermodynamically more favorable antioxidants than iAscH2 (75.1 kcal/mol) [48] and TocOH (79.7 kcal/mol) [48] in acetonitrile. The thermodynamic abilities of XH releasing hydrogen atoms decrease in the following order of HEH (68.7 kcal/mol) > BNAH (70.9 kcal/mol) > AcrH (73.0 kcal/mol).
Additionally, upon photoexcitation, the thermodynamic driving forces of HEH* (−3.7 kcal/mol), BNAH* (−2.9 kcal/mol), and AcrH* (−17.9 kcal/mol) releasing hydrogen atoms are significantly more negative than that of free hydrogen atoms (H•, 0.0 kcal/mol) in acetonitrile. This illustrates that HEH* (−3.7 kcal/mol), BNAH* (−2.9 kcal/mol), and AcrH* (−17.9 kcal/mol) are exceptionally strong hydrogen atom donors or antioxidants from a thermodynamic perspective. The thermodynamic abilities of XH* to release hydrogen atoms decrease in the following order: AcrH* (−17.9 kcal/mol) > HEH* (−3.7 kcal/mol) > BNAH* (−2.9 kcal/mol).
Ultimately, if the thermodynamic driving forces of XH* and XH releasing hydrogen atoms are compared, it is found that the thermodynamically hydrogen atom-donating abilities of XH* are greatly improved by photoexcitation. As hydrogen atom donors, the thermodynamic abilities of XH* and XH releasing hydrogen atom decrease in the order of AcrH* (−17.9 kcal/mol) > HEH* (−3.7 kcal/mol) > BNAH* (−2.9 kcal/mol) > HEH (68.7 kcal/mol) > BNAH (70.9 kcal/mol) > AcrH (73.0 kcal/mol).
Since XH* are much more effective hydrogen atom donors than their parents XH, the thermodynamic data lead us to take full advantage of the thermodynamic abilities of XH* in chemical reactions. For certain challenging unsaturated substrates (S), the direct hydrogen atoms transfer from XH to S is thermodynamically unfeasible, as represented by the reaction XH + S → X• + SH•. In such cases, chemists could seek the help of photoexcitation to convert XH into its excited XH* thereby facilitating the hydrogen atom transfer to the substrate, XH* + S → X• + SH• [8]. This strategy has been previously demonstrated to be effective. The thermodynamic driving forces associated with these processes provide critical insights. Specifically, the oxidation potentials of XH* are less than −2.66 V (vs. Fc), which corresponds to a thermodynamic driving force of −61.3 kcal/mol. In contrast, the subsequent thermodynamic driving forces for the release of protons from XH•+ range from 4.5 kcal/mol to 12.4 kcal/mol. These thermodynamic data suggest that the electron-releasing rate may be diffusion-controlled and several orders of magnitude larger than the following protons transfer rate, which clearly demonstrates that the overall hydrogen atom transfer process may undergo proton-coupled electron transfer (PCET) to activate unsaturated substrates [8,49,50,51] and the corresponding thermodynamic ability analysis of PCET is the same to that of XH* releasing hydrogen atoms.

2.6. Application of Thermodynamic Cards of XH and XH* to Reduction Reactions

As discussed earlier, photoexcited XH* are considered thermodynamically better hydride carriers than their parents XH in chemical reactions [5,6,7,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26]. To illustrate the application of the thermodynamic cards of XH and XH* in reduction reactions, the reductions of N,1-diphenylmethanimine (IM) by AcrH and AcrH* were examined. In our earlier work, the six thermodynamic driving forces of common imines accepting hydrides were determined in acetonitrile [52], and the thermodynamic card of N,1-diphenylmethanimine (IM) accepting hydrides is shown Scheme 9.
Scheme 5 and Scheme 9 provide a comprehensive understanding of the thermodynamic feasibility of hydride transfer from various donors to IM, highlighting the potential advantages of using photoexcited hydride donors (XH*) over their ground-state counterparts (XH) in facilitating such reductions. Based on the thermodynamic cards of AcrH and AcrH* (Scheme 5), as well as IM (Scheme 9), the thermodynamic analysis platforms (TAP) [3,52] of hydride transfer from AcrH and AcrH* to N,1-diphenylmethanimine (IM) are shown in Scheme 10 and Scheme 11, respectively.
From Scheme 10, the hydride transfer from AcrH to IM may involve six possible elementary steps and experience four potential mechanisms, including e + H• (Step 1 + Step 5), e + H+ + e (Step 1 + Step 6 + Step 4), H• + e (Step 3 + Step 4), and H− (Step 2) pathways. Considering the thermodynamic driving forces of six related elementary steps (Step 1–Step 6 in Scheme 10), three potential initiating steps are identified, that is, electron transfer (Step 1), hydrogen atom transfer (Step 3), and hydride transfer (Step 2). It is found from Scheme 10 that the thermodynamic driving force is 64.2 kcal/mol for Step 1 (ET), 46.2 kcal/mol for Step 3 (HT), and 40.3 kcal/mol for Step 2 (H−T). The thermodynamic driving forces for all three initiating steps (Step 1–Step 3) are greater than 40.0 kcal/mol, which are very high energy barriers to overcome. This indicates that the hydride transfer reaction from AcrH to IM is thermodynamically highly unfavorable or effectively impossible under these conditions.
In contrast, as can be seen from Scheme 11, the thermodynamic driving force for hydride transfer from AcrH* to IM is calculated to be −50.6 kcal/mol, based on the ΔHH−R(AcrH*) and ΔHH−A(IM) values. This negative value indicates the hydride transfer reaction from AcrH* to IM is thermodynamically feasible. Further analysis of the thermodynamic driving forces for the six possible elementary steps (Step 4–Step 9 in Scheme 11) reveals that these values range from −5.9 kcal/mol to −50.6 kcal/mol, all of which are significantly negative. This demonstrates that each of these elementary steps is thermodynamically feasible. Moreover, the three possible elementary steps initiated, namely Step 7 ΔG(ET) = −26.6 kcal/mol, Step 8 ΔH(HT) = −44.7 kcal/mol, and Step 9 ΔH(H−T) = −50.6 kcal/mol, have very large thermodynamic driving forces (<< −20 kcal/mol). Therefore, the following four mechanisms are all thermodynamically feasible for hydride transfer from AcrH* to IM: e + H• (Step 7 + Step 5), e + H+ + e (Step 7 + Step 6 + Step 4), H• + e (Step 9 + Step 4), and H− (Step 8) mechanisms. In practice, BNAH*, AcrH* and HEH* have been widely applied into photochemical synthesis, and the process of XH* releasing hydrides in chemical reactions may involve multiple mechanisms (Scheme 1b), including e [11,12,13,14,15,16], e + H• [17,18,19,20,21,22,23], e + H+ + e [24,25], H• + e [26], H [9,10,27,28] mechanisms. As for which one is the true hydride reduction mechanism between IM and AcrH*, it needs further validation and support in the experiment.
In fact, AcrH itself (81.1 kcal/mol) is a weak organic hydride and is unable to reduce IM via hydride transfer [3]. Meanwhile, after photoexcitation, AcrH* becomes a very strong hydride reductant (−9.8 kcal/mol), capable of easily reducing IM through hydride transfer. This highlights the significant impact of photoexcitation on enhancing the hydride-donating ability of XH*, transforming the hydride transfer reaction from thermodynamically unfeasible to feasible.

3. Experimental Section

3.1. Electrochemical Experiments

The potential determinations were carried out by CV and OSWV methods simultaneously via an electrochemical apparatus (BAS-100B) under the protection of Ar or N2 in the deaerated acetonitrile. The standard three-electrode system was used as follows: working electrode (glassy carbon), and reference electrode (0.01 M Ag/AgNO3 in 0.1 M nBu4NPF6/AN solution), as well as auxiliary electrode (platinum wire). The Fc/Fc+ couple was used as a reference for all measurements. Scans rate is 100 mV s−1. The concentration of the XH or X+ was ~1 mM in 0.1 M nBu4NPF6/AN solution. The estimated determination errors were smaller than 5 mV. Detailed electrochemical experiments, as well as the Eox(XH) values of Step 1 and Ered(X+) values of Step 4 for BNAH, HEH and AcrH in acetonitrile can be found in our previous work [3,4].

3.2. Isothermal Titration Experiments

The ΔHH−R(XH) values of Step 2 in acetonitrile were determined in our previous work by isothermal titration experiments [3,4]. The isothermal titration experiments were performed through a CSC4200 isothermal titration calorimeter (ITC) at 298 K in acetonitrile. The corresponding XH and Y+ were dissolved in the deaerated acetonitrile with a certain concentration, CXH and CY+. An injection of XH (10.0 μL) into Y+ solution was delivered in 1 s, and the time interval between every two injections was 300~500 s. Injections (denoted n times) were repeated over 10 times for each isothermal titration spectrum, and the heat changes were collected by an ITC detector. The molar reaction heat (ΔHr) between XH and Y+ was calculated by integrating every peak except the first one of the isothermal titration spectrum (denoted as ΔHint) by combing the known reaction concentration of XH (CXH) and injection times (n) through equation ΔHr = ΔHint/(n × 10 uL × CXH).

3.3. The Eox(XH*) Values Determination

The Eox(XH*) values are obtained by a combination of fluorescence and electrochemical technologies for BNAH* [31,32,33] and AcrH* [35,36]. The maximum emission wavelengths of XH*, λmax(em), were determined by a fluorescence spectrophotometer, which are the wavelengths of the strongest or highest peak from the related fluorescence emission spectrum. The excited-state energy of XH*, E00(XH*) (ev), was derived from λmax(em) of the XH* luminescence spectrum. The Eox(XH*) was obtained by subtracting the E00(XH*) from Eox(XH), Eox(XH*) = Eox(XH) − E00(XH*) [32]. In fact, E00 of photoexcited compounds can be estimated in a few different ways [41,42,43]. Similarly, the Eox(HEH*) value was derived from a combination of the UV-vis absorption spectrum of HEH and Eox(HEH) [34,41,42,43]. The Eox(XH*) values of Step 7 for BNAH* (−2.98 V vs. Fc) [31,32,33], HEH* (−2.66 V vs. Fc) [34,41,42,43] and AcrH* (−3.48 V vs. Fc) [35,36] are available in published work.

4. Conclusions

In summary, this work constructs detailed thermodynamic cards for three classic NADH models (BNAH, HEH, and AcrH), as well as their photoexcited states (BNAH*, HEH*, and AcrH*) in acetonitrile, focusing on their ability to release hydrides. The analysis reveals that photoexcitation significantly enhances the reducing abilities of these compounds, making XH* exceptionally strong electron, hydrogen atom, and hydride donors compared to their ground-state counterparts (XH).
Specifically, as electron donors, the thermodynamic abilities of XH* and XH to release electrons decrease in the order of AcrH* (−3.48 V vs. Fc) > BNAH* (−2.98 V vs. Fc) > HEH* (−2.66 V vs. Fc) > BNAH (0.219 V vs. Fc) > AcrH (0.460 V vs. Fc) > HEH (0.479 V vs. Fc). As hydride donors, the thermodynamic abilities of XH* and XH to release hydrides decrease in the order of AcrH* (−9.8 kcal/mol) ≈ BNAH* (−9.6 kcal/mol) > HEH* (−3.1 kcal/mol) > BNAH (64.2 kcal/mol) > HEH (69.3 kcal/mol) > AcrH (81.1 kcal/mol). As hydrogen atom donors, the thermodynamic abilities of XH* and XH to release hydrogen atom decrease in the order of AcrH* (−17.9 kcal/mol) > HEH* (−3.7 kcal/mol) > BNAH* (−2.9 kcal/mol) > HEH (68.7 kcal/mol) > BNAH (70.9 kcal/mol) > AcrH (73.0 kcal/mol). Among the three classic NADH models, AcrH* emerges as the thermodynamically superior donor of electrons, hydrides, and hydrogen atoms. Its exceptional reducing abilities highlight the potential of photoexcited organic hydrides in facilitating challenging reductions and activating inert substrates.
These findings suggest that NADH models, particularly their photoexcited states, may have broader applications in organic synthesis and photochemical reactions due to their enhanced reducing capabilities. The impressive thermodynamic cards of XH* inspire further investigation into the excited wavelengths, excited potentials, and excited-state stabilities of more organic hydrides. This research direction holds promise for discovering novel and highly effective photoexcited organic hydride reductants with potential applications in various chemical transformations.

Author Contributions

Formal analysis and investigation, B.-C.Q.; supervision, X.-Q.Z.; writing—original draft, G.-B.S. All authors have read and agreed to the published version of the manuscript.

Funding

This study was supported by the doctoral scientific research foundation of Jining Medical University and Health Commission of Shandong Province (202313051336).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data are contained within the article.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Xie, N.; Zhang, L.; Gao, W.; Huang, C.; Huber, P.E.; Zhou, X.; Li, C.; Shen, G.; Zou, B. Metabolism: Pathophysiologic Mechanisms and Therapeutic Potential. Signal Transduct. Target. Ther. 2020, 5, 227. [Google Scholar] [PubMed]
  2. Verkhovsky, M.I.; Bogachev, A.V.; Pivtsov, A.V.; Bertsova, Y.V.; Fedin, M.V.; Bloch, D.A.; Kulik, L.V. sodium-dependent movement of covalently bound FMN residue(s) in Na+-translocating NADH: Quinone oxidoreductase. Biochemistry 2012, 51, 5414–5421. [Google Scholar] [CrossRef] [PubMed]
  3. Shen, G.-B.; Qian, B.-C.; Fu, Y.-H.; Zhu, X.-Q. Thermodynamics of the Elementary Steps of Organic Hydride Chemistry Determined in Acetonitrile and their Applications. Org. Chem. Front. 2022, 9, 6001–6062. [Google Scholar] [CrossRef]
  4. Zhu, X.-Q.; Tan, Y.; Cao, C.-T. Thermodynamic diagnosis of the properties and mechanism of dihydropyridine-type compounds as hydride source in acetonitrile with “Molecule ID Card”. J. Phys. Chem. B 2010, 114, 2058–2075. [Google Scholar] [CrossRef]
  5. Lee, Y.-M.; Nam, W.; Fukuzumi, S. Redox Catalysis Via Photoinduced Electron Transfer. Chem. Sci. 2023, 14, 4205–4218. [Google Scholar] [CrossRef]
  6. Yedase, G.S.; Sreelakshmi Venugopal, S.; Arya, P.; Yatham, V.R. Catalyst-free Hantzsch Ester-mediated Organic Transformations Driven by Visible light. Asian J. Org. Chem. 2022, 11, e202200478. [Google Scholar] [CrossRef]
  7. Huang, W.; Cheng, X. Hantzsch Esters as Multifunctional Reagents in Visible-Light Pho- toredox Catalysis. Synlett 2017, 28, 148–158. [Google Scholar]
  8. Murray, P.R.D.; Cox, J.H.; Chiappini, N.D.; Roos, C.B.; McLoughlin, E.A.; Hejna, B.G.; Nguyen, S.T.; Ripberger, H.H.; Ganley, J.M.; Tsui, E.; et al. Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis. Chem. Rev. 2022, 122, 2017–2291. [Google Scholar] [CrossRef]
  9. Zheng, C.; You, S.-L. Transfer Hydrogenation with Hantzsch Esters and Related Organic Hydride Donors. Chem. Soc. Rev. 2012, 41, 2498–2518. [Google Scholar] [CrossRef]
  10. Rueping, M.; Dufour, J.; Schoepke, F.R. Advances in Catalytic Metal-Free Reductions: From Bioinspired Concepts to Applications in the Organocatalytic Synthesis of Pharmaceuticals and Natural Products. Green Chem. 2011, 13, 1084–1105. [Google Scholar] [CrossRef]
  11. Huang, B.; Bu, X.-S.; Xu, J.; Dai, J.-J.; Feng, Y.-S.; Xu, H.-J. Metal-Free, Visible-Light-Mediated Direct C-H Trifluoromethylation of Hydrazones with NADH Coenzyme Model Catalyst. Asian J. Org. Chem. 2018, 7, 137–140. [Google Scholar] [CrossRef]
  12. Jiang, J.; Zhang, W.-M.; Dai, J.-J.; Xu, J.; Xu, H.-J. Visible-Light-Promoted C–H Arylation by Merging Palladium Catalysis with Organic Photoredox Catalysis. J. Org. Chem. 2017, 82, 3622–3630. [Google Scholar] [CrossRef] [PubMed]
  13. Zhou, Z.-Z.; Zhai, X.-F.; Zhang, S.-L.; Xia, K.-J.; Ding, H.; Song, X.-R.; Tian, W.-F.; Liang, Y.-M.; Xiao, Q. Photo-Induced Nickel-Mediated Cross-Electrophile Coupling for Alkylated Allenes Via Electron Donor–Acceptor Complexes. Org. Chem. Front. 2023, 10, 298–303. [Google Scholar] [CrossRef]
  14. Kammer, L.M.; Badir, S.O.; Hu, R.-M.; Molander, G.A. Photoactive Electron Donor–Acceptor Complex Platform for Ni-Mediated C(sp3)–C(sp2) Bond Formation. Chem. Sci. 2021, 12, 5450–5457. [Google Scholar] [CrossRef]
  15. Xu, X.; Min, Q.-Q.; Lia, N.; Liu, F. Visible Light-Promoted Umpolung Coupling of Aryl Tri-/Difluoroethanones with 2-Alkenylpyridines. Chem. Commun. 2018, 54, 11017–11020. [Google Scholar] [CrossRef]
  16. Patel, S.S.; Kumara, D.; Tripathi, C.B. Brønsted Acid Catalyzed Radical Addition to Quinone Methides. Chem. Commun. 2021, 57, 5151–5154. [Google Scholar] [CrossRef]
  17. Yu, Z.; Kong, Y.; Li, B.; Su, S.; Rao, J.; Gao, Y.; Tu, T.; Chen, H.; Liao, K. HTE- and AI-Assisted Development of DHP-Catalyzed Decarboxylative Selenation. Chem. Commun. 2023, 59, 2935–2938. [Google Scholar] [CrossRef]
  18. Nagode, S.B.; Kant, R.; Rastogi, N. Hantzsch Ester-Mediated Benzannulation of Diazo Compounds under Visible Light Irradiation. Org. Lett. 2019, 21, 6249–6254. [Google Scholar] [CrossRef]
  19. Jung, J.; Kim, J.; Park, G.; You, Y.; Cho, E.J. Selective Debromination and a-Hydroxylation of a-Bromo Ketones Using Hantzsch Esters as Photoreductants. Adv. Synth. Catal. 2016, 358, 74–80. [Google Scholar] [CrossRef]
  20. Panferova, L.I.; Tsymbal, A.V.; Levin, V.V.; Struchkova, M.I.; Dilman, A.D. Reactions of gem-Difluorinated Phosphonium Salts Induced by Light. Org. Lett. 2016, 18, 996–999. [Google Scholar] [CrossRef]
  21. Liu, Y.; Lin, S.; Zhang, D.; Song, B.; Jin, Y.; Hao, E.; Shi, L. Photochemical Nozaki−Hiyama−Kishi Coupling Enabled by Excited Hantzsch Ester. Org. Lett. 2022, 24, 3331–3336. [Google Scholar] [CrossRef] [PubMed]
  22. Wu, J.; Grant, P.S.; Li, X.; Noble, A.; Aggarwal, V.K. Catalyst-Free Deaminative Functionalizations of Primary Amines via Photoinduced Single-Electron Transfer. Angew. Chem. Int. Ed. 2019, 58, 5697–5701. [Google Scholar] [CrossRef] [PubMed]
  23. Nagode, S.B.; Kant, R.; Rastogi, N. Hantzsch Ester-Mediated Synthesis of Phenanthridines under Visible Light Irradiation. Chem. Asian J. 2020, 15, 3513–3518. [Google Scholar] [CrossRef] [PubMed]
  24. Chowdhury, R.; Yu, Z.; Tong, M.L.; Kohlhepp, S.V.; Yin, X.; Mendoza, A. Decarboxylative Alkyl Coupling Promoted by NADH and Blue Light. J. Am. Chem. Soc. 2020, 142, 20143–20151. [Google Scholar] [CrossRef]
  25. Johansen, C.M.; Boyd, E.A.; Peters, J.C. Catalytic Transfer Hydrogenation of N2 to NH3 via A Photoredox Catalysis Strategy. Sci. Adv. 2022, 8, eade3510. [Google Scholar] [CrossRef]
  26. Huang, W.; Chen, W.; Wang, G.; Li, J.; Cheng, X.; Li, G. Thiyl-Radical-Catalyzed Photoreductive Hydrodifluoroacetamidation of Alkenes with Hantzsch Ester as a Multifunctional Reagent. ACS Catal. 2016, 6, 7471–7474. [Google Scholar] [CrossRef]
  27. Yu, T.; Higashi, M.; Cembran, A.; Gao, J.; Truhlar, D.G. Concerted Hydrogen Atom and Electron Transfer Mechanism for Catalysis by Lysine-Specific Demethylase. J. Phys. Chem. B 2013, 117, 8422–8429. [Google Scholar] [CrossRef]
  28. Shen, G.-B.; Qian, B.-C.; Zhang, G.-S.; Luo, G.-Z.; Fu, Y.-H.; Zhu, X.-Q. Thermodynamics Regulated Organic Hydride/Acid Pairs as Novel Organic Hydrogen Reductants. Org. Chem. Front. 2022, 9, 6833–6848. [Google Scholar] [CrossRef]
  29. Zhu, X.-Q.; Zhang, M.-T.; Yu, A.; Wang, C.-H.; Cheng, J.-P. Hydride, Hydrogen Atom, Proton, and Electron Transfer Driving Forces of Various Five-Membered Heterocyclic Organic Hydrides and their Reaction Intermediates in Acetonitrile. J. Am. Chem. Soc. 2008, 130, 2501–2516. [Google Scholar] [CrossRef]
  30. Zhu, X.-Q.; Zhang, M.; Liu, Q.-Y.; Wang, X.-X.; Zhang, J.-Y.; Cheng, J.-P. A Facile Experimental Method to Determine the Hydride Affinity of Polarized Olefins in Acetonitrile. Angew. Chem. Int. Ed. 2006, 45, 3954–3957. [Google Scholar] [CrossRef]
  31. Fukuzumi, S.; Inada, O.; Suenobu, T. Mechanisms of Electron-Transfer Oxidation of NADH Analogues and Chemiluminescence. Detection of the Keto and Enol Radical Cations. J. Am. Chem. Soc. 2003, 125, 4808–4816. [Google Scholar] [CrossRef] [PubMed]
  32. Fukuzumi, S.; Koumitsu, S.; Katsuhik Hironaka, K.; Tanaka, T. Energetic Comparison between Photoinduced Electron-Transfer Reactions from NADH Model Compounds to Organic and Inorganic Oxidants and Hydride-Transfer Reactions from NADH Model Compounds to p-Benzoquinone Derivatives. J. Am. Chem. Soc. 1987, 109, 305–316. [Google Scholar] [CrossRef]
  33. Fukuzumi, S.; Hironaka, K.; Tanaka, T. Photoreduction of Alkyl Halides by an NADH Model Compound. An Electron-Transfer Chain Mechanism. J. Am. Chem. Soc. 1983, 105, 4722–4727. [Google Scholar] [CrossRef]
  34. Ji, P.; Zhang, Y.; Wei, Y.; Huang, H.; Hu, W.; Mariano, P.A.; Wang, W. Visible-Light-Mediated, Chemo- and Stereoselective Radical Process for the Synthesis of C-Glycoamino Acids. Org. Lett. 2019, 21, 3086–3092. [Google Scholar] [CrossRef]
  35. Ishikawa, M.; Fukuzumi, S. 10-Methylacridine Derivatives Acting as Efficient and Stable Photocatalysts in Reductive Dehalogenation of Halogenated Compounds with Sodium Borohydride via Photoinduced Electron Transfer. J. Am. Chem. Soc. 1990, 112, 8864–8870. [Google Scholar] [CrossRef]
  36. Fukuzumi, S.; Ishikawa, M.; Tanaka, T. Mechanisms of Photo-Oxidation of NADH Model Compounds by Oxygen. J. Chem. Soc. Perkin Trans. II 1989, 8, 1037–1045. [Google Scholar] [CrossRef]
  37. Strieth-Kalthoff, F.; James, M.J.; Teders, M.; Pitzer, L.; Glorius, F. Energy Transfer Catalysis Mediated by Visible Light: Principles, Applications, Directions. Chem. Soc. Rev. 2018, 47, 7190–7202. [Google Scholar] [CrossRef]
  38. Zhu, D.-L.; Wu, Q.; Li, H.-Y.; Li, H.-X.; Lang, J.-P. Hantzsch Ester as a Visible-Light Photoredox Catalyst for Transition-Metal-Free Coupling of Arylhalides and Arylsulfinates. Chem. Eur. J. 2020, 26, 3484–3488. [Google Scholar] [CrossRef]
  39. Pavlishchuk, V.V.; Addison, A.W. Conversion Constants for Redox Potentials Measured Versus Different Reference Electrodes in Acetonitrile Solutions at 25 °C. Inorg. Chim. Acta 2000, 298, 97–102. [Google Scholar] [CrossRef]
  40. Arnett, E.M.; Amarnath, K.; Harvey, N.G.; Cheng, J.-P. Determination and Interrelation of Bond Heterolysis and Homolysis Energies in Solution. J. Am. Chem. Soc. 1990, 112, 344–355. [Google Scholar] [CrossRef]
  41. Wu, Y.; Kim, D.; Teets, T.S. Photophysical Properties and Redox Potentials of Photosensitizers for Organic Photoredox Transformations. Synlett 2022, 33, 1154–1179. [Google Scholar]
  42. Buzzetti, L.; Crisenza, G.E.M.; Melchiorre, P. Mechanistic Studies in Photocatalysis. Angew. Chem. Int. Ed. 2019, 58, 3730–3747. [Google Scholar] [CrossRef] [PubMed]
  43. Shon, J.-H.; Sittel, S.; Teets, T.S. Synthesis and Characterization of Strong Cyclometalated Iridium Photoreductants for Application in Photocatalytic Aryl Bromide Hydrodebromination. ACS Catal. 2019, 9, 8646–8658. [Google Scholar] [CrossRef]
  44. Yu, X.-Y.; Chen, J.-R.; Xiao, W.-J. Visible Light-Driven Radical-Mediated C−C Bond Cleavage/Functionalization in Organic Synthesis. Chem. Rev. 2021, 121, 506–561. [Google Scholar] [CrossRef] [PubMed]
  45. Chan, A.Y.; Perry, I.B.; Bissonnette, N.B.; Buksh, B.F.; Edwards, G.A.; Frye, L.I.; Garry, O.L.; Lavagnino, M.N.; Li, B.X.; Liang, Y.; et al. Metallaphotoredox: The Merger of Photoredox and Transition Metal Catalysis. Chem. Rev. 2022, 122, 1485–1542. [Google Scholar] [CrossRef]
  46. Leitch, J.A.; Rossolini, T.; Rogova, T.; Maitland, J.A.P.; Dixon, D.J. α-Amino Radicals via Photocatalytic Single-Electron Reduction of Imine Derivatives. ACS Catal. 2020, 10, 2009–2025. [Google Scholar] [CrossRef]
  47. Heiden, Z.M.; Lathem, A.P. Establishing the Hydride Donor Abilities of Main Group Hydrides. Organometallics 2015, 34, 1818–1827. [Google Scholar] [CrossRef]
  48. Warren, J.J.; Tronic, T.A.; Mayer, J.M. Thermochemistry of Proton-Coupled Electron Transfer Reagents and Its Implications. Chem. Rev. 2010, 110, 6961–7001. [Google Scholar] [CrossRef]
  49. Agarwal, R.G.; Coste, S.C.; Groff, B.D.; Heuer, A.M.; Noh, H.; Parada, G.A.; Wise, C.F.; Nichols, E.M.; Warren, J.J.; Mayer, J.M. Free Energies of Proton-Coupled Electron Transfer Reagents and Their Applications. Chem. Rev. 2022, 122, 1–49. [Google Scholar] [CrossRef]
  50. Warburton, R.E.; Soudackov, A.V.; Hammes-Schiffer, S. Theoretical Modeling of Electrochemical Proton-Coupled Electron Transfer. Chem. Rev. 2022, 122, 10599–10650. [Google Scholar] [CrossRef]
  51. Yang, J.-D.; Xue, J.; Cheng, J.-P. Understanding the Role of Thermodynamics in Catalytic Imine Reductions. Chem. Soc. Rev. 2019, 48, 2913–2926. [Google Scholar] [CrossRef] [PubMed]
  52. Zhu, X.-Q.; Liu, Q.-Y.; Chen, Q.; Mei, L.-R. Hydride, Hydrogen, Proton, and Electron Affinities of Imines and Their Reaction Intermediates in Acetonitrile and Construction of Thermodynamic Characteristic Graphs (TCGs) of Imines as a “Molecule ID Card”. J. Org. Chem. 2010, 75, 789–808. [Google Scholar] [CrossRef] [PubMed]
Molecules 30 01053 sch001
Scheme 1. (a) The chemical structures of BNAH, HEH, and AcrH; (b) XH and XH* act as electron, hydrogen atom, and hydride donors in chemical reactions (PCE refers to proton-coupled electrons and ECH refers to electron-coupled hydrogen atoms).
Scheme 1. (a) The chemical structures of BNAH, HEH, and AcrH; (b) XH and XH* act as electron, hydrogen atom, and hydride donors in chemical reactions (PCE refers to proton-coupled electrons and ECH refers to electron-coupled hydrogen atoms).
Molecules 30 01053 sch001
Molecules 30 01053 sch002
Scheme 2. The nine possible elementary steps of XH and XH* releasing hydrides.
Scheme 2. The nine possible elementary steps of XH and XH* releasing hydrides.
Molecules 30 01053 sch002
Molecules 30 01053 sch003
Scheme 3. Thermodynamic card of BNAH and BNAH* releasing hydrides in acetonitrile.
Scheme 3. Thermodynamic card of BNAH and BNAH* releasing hydrides in acetonitrile.
Molecules 30 01053 sch003
Molecules 30 01053 sch004
Scheme 4. Thermodynamic card of HEH and HEH* releasing hydrides in acetonitrile.
Scheme 4. Thermodynamic card of HEH and HEH* releasing hydrides in acetonitrile.
Molecules 30 01053 sch004
Molecules 30 01053 sch005
Scheme 5. Thermodynamic card of AcrH and AcrH* releasing hydrides in acetonitrile.
Scheme 5. Thermodynamic card of AcrH and AcrH* releasing hydrides in acetonitrile.
Molecules 30 01053 sch005
Molecules 30 01053 sch006
Scheme 6. Comparisons of oxidation potentials of XH* and related XH, along with the oxidation potentials of common electron donors in acetonitrile (reference electrode Ag/AgNO3).
Scheme 6. Comparisons of oxidation potentials of XH* and related XH, along with the oxidation potentials of common electron donors in acetonitrile (reference electrode Ag/AgNO3).
Molecules 30 01053 sch006
Molecules 30 01053 sch007
Scheme 7. Comparisons of hydride-releasing abilities of XH* and related XH, along with the hydride-releasing abilities of common hydride donors in acetonitrile.
Scheme 7. Comparisons of hydride-releasing abilities of XH* and related XH, along with the hydride-releasing abilities of common hydride donors in acetonitrile.
Molecules 30 01053 sch007
Molecules 30 01053 sch008
Scheme 8. Comparisons of hydrogen atom-releasing abilities of XH* and related XH, along with that of common hydrogen atom donors in acetonitrile (R group in TocOH refers to (4R,8R)-4,8,12-trimethyltridecyl).
Scheme 8. Comparisons of hydrogen atom-releasing abilities of XH* and related XH, along with that of common hydrogen atom donors in acetonitrile (R group in TocOH refers to (4R,8R)-4,8,12-trimethyltridecyl).
Molecules 30 01053 sch008
Molecules 30 01053 sch009
Scheme 9. Thermodynamic card of N,1-diphenylmethanimine (IM) accepting hydrides in acetonitrile.
Scheme 9. Thermodynamic card of N,1-diphenylmethanimine (IM) accepting hydrides in acetonitrile.
Molecules 30 01053 sch009
Molecules 30 01053 sch010
Scheme 10. Thermodynamic analysis platform (TAP) of hydride transfer from AcrH to N,1-diphenylmethanimine (IM) in acetonitrile.
Scheme 10. Thermodynamic analysis platform (TAP) of hydride transfer from AcrH to N,1-diphenylmethanimine (IM) in acetonitrile.
Molecules 30 01053 sch010
Molecules 30 01053 sch011
Scheme 11. Thermodynamic analysis platform (TAP) of hydride transfer from AcrH* to N,1-diphenylmethanimine (IM) in acetonitrile.
Scheme 11. Thermodynamic analysis platform (TAP) of hydride transfer from AcrH* to N,1-diphenylmethanimine (IM) in acetonitrile.
Molecules 30 01053 sch011
Table 1. Thermodynamic data of nine potential elementary steps of BNAH, HEH, and AcrH and their related single excited states (BNAH*, HEH*, and AcrH*) releasing hydrides in acetonitrile.
Table 1. Thermodynamic data of nine potential elementary steps of BNAH, HEH, and AcrH and their related single excited states (BNAH*, HEH*, and AcrH*) releasing hydrides in acetonitrile.
Step XProcessParametersUnitBNAHHEHAcrH
Step 1XH → XH•+ + eEox(XH)V vs. Fc0.2190.4790.460
Step 2XH → X+ + H−ΔHH−R(XH)kcal/mol64.269.381.1
Step 3XH → X• + H•ΔHHR(XH)kcal/mol70.968.773.0
Step 4X• → X+ + eEox(X•)V vs. Fc−1.419−1.112−0.789
Step 5XH•+ → X+ + H•ΔHHR(XH•+)kcal/mol32.932.044.2
Step 6XH•+ → X• + H+ΔHPR(XH•+)kcal/mol12.44.59.2
Step 7XH* → XH•+ + eEox(XH*)V vs. Fc−2.98−2.66−3.48
Step 8XH* → X+ + H−
XH* → X+ + ECH		ΔHH−R(XH*)kcal/mol−9.6−3.1−9.8
Step 9XH* → X• + H•
XH* → X• + PCE		ΔHHR(XH*)kcal/mol−2.9−3.7−17.9
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Qian, B.-C.; Zhu, X.-Q.; Shen, G.-B. Thermodynamic Cards of Classic NADH Models and Their Related Photoexcited States Releasing Hydrides in Nine Elementary Steps and Their Applications. Molecules 2025, 30, 1053. https://doi.org/10.3390/molecules30051053

AMA Style

Qian B-C, Zhu X-Q, Shen G-B. Thermodynamic Cards of Classic NADH Models and Their Related Photoexcited States Releasing Hydrides in Nine Elementary Steps and Their Applications. Molecules. 2025; 30(5):1053. https://doi.org/10.3390/molecules30051053

Chicago/Turabian Style

Qian, Bao-Chen, Xiao-Qing Zhu, and Guang-Bin Shen. 2025. "Thermodynamic Cards of Classic NADH Models and Their Related Photoexcited States Releasing Hydrides in Nine Elementary Steps and Their Applications" Molecules 30, no. 5: 1053. https://doi.org/10.3390/molecules30051053

APA Style

Qian, B.-C., Zhu, X.-Q., & Shen, G.-B. (2025). Thermodynamic Cards of Classic NADH Models and Their Related Photoexcited States Releasing Hydrides in Nine Elementary Steps and Their Applications. Molecules, 30(5), 1053. https://doi.org/10.3390/molecules30051053

Article Metrics

Back to TopTop