The effect of substituents on the reactivity of dichloridotriphenylphosphinoruthenium(II) complexes: kinetic and mechanistic study

Article abstract of DOI:10.1080/00958972.2021.1904234

The rates of substitution of chloro ligands from a series of ruthenium(II) complexes, [Ru(κ³-L)(PPh₃)Cl₂] (L = 2,2′:6′,2′′-terpyridine, 1; 4′-(4-methylphenyl)-2,2′:6′,2′′-terpyridine, 2; 4,4′4″-tri-tert-butyl-2,2′:6′,2′′-terpyridine, 3; 4′-(4-chlorophenyl)-2,2′:6′,2′′-terpyridine, 4; 4-chloro-2,2′:6′,2′′-terpyridine, 5 and 2,6-bis(2-pyrazolyl)pyridine, 6), by thiourea nucleophiles was investigated under pseudo-first-order conditions in methanol as a function of nucleophile concentration and temperature. The chloro ligands were substituted in two steps and the reactivity trend was 4 > 5 > 2 > 1 > 6. Complexes 2 and 3 having donor substituents on the 2,2′:6′,2′′-terpyridine backbone experience a trans-effect making them more reactive than 1. Complexes 4 and 5 are more reactive than 1 due to enhanced π-back-bonding brought about by electron-withdrawing substituents on their 2,2′:6′,2′′-terpyridine backbones. The reactivity of 4 is higher than 5 due to greater electron acceptor-ability of the chlorophenyl substituent than the chloro substituent in 5. The 2,6-bis(pyrazolyl)pyridine ligand in 6 retards the reactivity of the complex compared to 1 due to the cis-donor effect of the pyrazole. The reactivity of the complexes is associative for all nucleophiles in step one and only thiourea in step two. The substitution reactions proceed by a steady changeover from an associative interchange mechanism (I _a) to a dissociative interchange (I _d) mechanism on increasing steric hindrance.

Full text of DOI:10.1080/00958972.2021.1904234

Journal of Coordination Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gcoo20
The effect of substituents on the reactivity of
dichloridotriphenylphosphinoruthenium(II)
complexes: kinetic and mechanistic study
Meshack K. Sitati, Gershom Kyalo Mutua, Daniel O. Onunga, Deogratius
Jaganyi & Allen Mambanda
To cite this article: Meshack K. Sitati, Gershom Kyalo Mutua, Daniel O. Onunga,
Deogratius Jaganyi & Allen Mambanda (2021): The effect of substituents on the reactivity of
dichloridotriphenylphosphinoruthenium(II) complexes: kinetic and mechanistic study, Journal of
Coordination Chemistry, DOI: 10.1080/00958972.2021.1904234
To link to this article: https://doi.org/10.1080/00958972.2021.1904234
View supplementary material
Published online: 24 Mar 2021.
Submit your article to this journal
Article views: 75
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=gcoo20

JOURNAL OF COORDINATION CHEMISTRY
https://doi.org/10.1080/00958972.2021.1904234
The effect of substituents on the reactivity of
dichloridotriphenylphosphinoruthenium(II) complexes:
kinetic and mechanistic study
Meshack K. Sitatia,b, Gershom Kyalo Mutuaa,c, Daniel O. Onungaa,d, Deogratius
Jaganyie,f
and Allen Mambandaa
aSchool of Chemistry and Physics, University of KwaZulu-Natal, Scottsville, Pietermaritzburg, South
b
Africa; Department of Mathematics and Physical Sciences, Maasai Mara University, Narok, Kenya;
cDepartment of Pure and Applied Chemistry, School of Natural Sciences, Masinde Muliro University
d
of Science and Technology, Kakamega, Kenya; Department of Chemistry, Maseno University,
e
Maseno, Kenya; School of Pure and Applied Sciences, Mount Kenya University, Thika, Kenya;
fFaculty of Applied Sciences, Department of Chemistry, Durban University of Technology, Durban,
South Africa
ABSTRACT
ARTICLE HISTORY
Received 1 August 2020
Accepted 18 February 2021
The rates of substitution of chloro ligands from a series of
ruthenium(II) complexes, [Ru(j3-L)(PPh3)Cl2] (L ¼ 2,20:60,200-terpyri-
dine, 1; 40-(4-methylphenyl)-2,20:60,200-terpyridine, 2; 4,40400-tri-tert-
butyl-2,20:60,200-terpyridine, 3; 40-(4-chlorophenyl)-2,20:60,200-terpyri-
dine, 4; 4-chloro-2,20:60,200-terpyridine, 5 and 2,6-bis(2-pyrazolyl)-
pyridine, 6), by thiourea nucleophiles was investigated under
pseudo-first-order conditions in methanol as a function of nucleo-
phile concentration and temperature. The chloro ligands were
substituted in two steps and the reactivity trend was 4 > 5 >
2 > 1 > 6. Complexes 2 and 3 having donor substituents on the
2,20:60,200-terpyridine backbone experience a trans-effect making
them more reactive than 1. Complexes 4 and 5 are more reactive
than 1 due to enhanced p-back-bonding brought about by elec-
tron-withdrawing substituents on their 2,20:60,200-terpyridine back-
bones. The reactivity of 4 is higher than 5 due to greater electron
acceptor-ability of the chlorophenyl substituent than the chloro
substituent in 5. The 2,6-bis(pyrazolyl)pyridine ligand in 6 retards
the reactivity of the complex compared to 1 due to the cis-donor
effect of the pyrazole. The reactivity of the complexes is associa-
tive for all nucleophiles in step one and only thiourea in step
two. The substitution reactions proceed by a steady changeover
from an associative interchange mechanism (Ia) to a dissociative
interchange (Id) mechanism on increasing steric hindrance.
KEYWORDS
Cis-effect; kinetics;
ruthenium(II); substitution;
thiourea; trans-effect
CONTACT Meshack K. Sitati
meshacksitati@gmail.com
School of Chemistry and Physics, University of
KwaZulu-Natal, Private Bag X01, Scottsville, Pietermaritzburg 3209, South Africa; Deogratius Jaganyi
deojaganyi@gmail.com
Thika, Kenya.
School of Pure and Applied Sciences, Mount Kenya University, P.O. Box 342-01000,
Supplemental data for this article can be accessed here.
ß 2021 Informa UK Limited, trading as Taylor & Francis Group

2
M. K. SITATI ET AL.
1. Introduction
The coordination chemistry of Ru(II) has been a focus due to its versatile applications,
particularly in the area of DNA intercalation and protein binding [1]. Tridentate ligands
such as 2,20:60,200-terpyridine (tpy) and its derivatives have been used extensively by
Metcalfe et al. in the synthesis of Ru complexes [2]. The tpy ligand and its derivatives
have been widely studied as chelating ligands because they form strong r-bonds with
metals forming complexes with many applications [3]. The tpy type ligands have also
shown cytotoxicity against several human tumor cell lines [4]. A number of complexes
incorporating these ligands have been reported to interact with DNA through electro-
static interaction, intercalation, and groove binding [5].
Many Ru(tpy) complexes are potent DNA intercalators. For example, the activity of
tpyRu(III)Cl3 against L1210 leukemia cells compares favorably to that of cisplatin [6].
The physical and chemical properties and DNA binding capacity of Ru(tpy) complexes
and hence their interaction with DNA can be varied by the introduction of different
substituents on the tpy ligand [7]. Turro and coworkers reported DNA photo-cleavage
by Ru(tpy)-3-(pyrid-2-yl)dipyrido(3,2,-a:20,30-c)phenazine in the presence of oxygen [8].
The substituent ensured favorable intercalating interactions by the planar groups at
the sites of DNA cleavage. Complexes incorporating tpy and N-N bidentate ligands
like [Ru(tpy)(bipyridine)O]2þ and Ru(tpy)(bipyridine)OH]2þ were also found to be effi-
cient DNA photocleaving agents [9]. The DNA cleavage of [Ru(tpy)N,N,N,N-
tetramethylenediamine)OH2]2þ was also confirmed by cyclic voltammetry [10–12].
The complexes [Ru(j3-L)(PPh3)2-Cl]þ (L ¼ tpy or 2,4,6-tris(2-pyridyl)-1,3,5-triazine
ligands) have been reported to have bio-catalytic properties [13]. Replacement of one
of the triphenyl phosphine ligands by a chloro ligand gave Ru(II) complexes, [Ru(j3-
L)(PPh3)Cl2] (L ¼ tpy or 2,4,6-tris(2-pyridyl)-1,3,5-triazine ligands) which lowers the steric
hindrance and increases DNA binding [1]. Data on the biochemical interactions of
[Ru(j3-L)(PPh3)2-Cl]þ and similar complexes cover mainly their binding interaction with
DNA yet potential anticancer metal complexes interact with all sorts of bio-nucleo-
philes in a biological environment. Investigating the reactivity of the compounds with
biomolecules helps in understanding their behavior in biological systems.
Understanding their stability, the nature of interactions and the general desire to

JOURNAL OF COORDINATION CHEMISTRY
3
Figure 1. Chemical structure of the neutral ruthenium(II) complexes studied.
investigate the role played by varying the nature of substituents attached at the
4-position of the tpy ligand on the rate of chloro substitution reactions from the neu-
tral Ru(II) complexes motivated this study. The general formula of the compounds of
interest is [Ru(j3-L)(PPh3)Cl2] (where L ¼ 2,20:60,200-terpyridine, 1; 40-(4-methylphenyl)-
2,20:60,200-terpyridine, 2; 4,40400-tri-tert-butyl-2,20:60,200-terpyridine, 3; 40-(4-chlorophenyl)-
2,20:60,200-terpyridine, 4; 4-chloro-2,20:60,200-terpyridine, 5 and 2,6-bis(2-pyrazolyl)pyri-
dine, 6). The chemical structures of the complexes investigated are shown in Figure 1.
Neutral thiourea-based nucleophiles of different steric properties were used, thiourea
(TU), 1,3-dimethylthiourea (DMTU) and 1,1,3,3-tetramethylthiourea (TMTU).
Information on the rate of substitution of potential anticancer agents is important
to infer their interactions with biological nucleophiles. In addition to the experimental
studies, computational studies were performed using Gaussian 09 W program suite to
gain insight into the stereo-electronic properties of the complexes.
2. Experimental
2.1. Materials
Solvents and other reagents such as 2,20:60,200-terpyridine, 40-(4-methylphenyl)-2,
20:60,200-terpyridine,4,40400-tri-tert-butyl-2,20:60,200-terpyridine, 40-(4-chlorophenyl)-2,20:60,

4
M. K. SITATI ET AL.
200-terpyridine, 4-chloro-2,20:60,200-terpyridine, 2,6-bis(2-pyrazolyl)pyridineandtris(triphe-
nylphosphine)-Ru(II)dichloride were purchased from Sigma Aldrich and used as received.
2.2. Syntheses of the complexes
The syntheses of the complexes were carried out according to a modified standard
literature method [1, 14].
Dichloro(2,20:60,200-terpyridine)(triphenylphosphino)ruthenium(II) (1). 2,20:60,200-
Terpyridine
(46.65 mg,
0.2 mmol)
and
tris(triphenylphosphine)Ru(II)dichloride
(191.77 mg, 0.2 mmol) were mixed in 30 mL of benzene and the mixture heated under
reflux for 6 h. After cooling to room temperature, the precipitate was collected by fil-
tration, washed several times with cold benzene and diethyl ether then dried under
vacuum. Yield: 90.11 mg (67.5%), brown solid. 1H NMR (400 MHz, DMF-d7, ppm):
d ¼ 9.51 (d, 2H); 8.44 (m, 2H); 8.07 (t, 2H); 7.80 (m, 1H); 7.72 (t, 2H); 7.54 (m, 8H); 7.39
(m, 9H). 31P NMR (400 MHz, DMF-d7, ppm): d ¼ 41.18. 13C NMR (400 MHz, DMF-d7,
ppm): d ¼ 121.98, 126.36, 128.39, 132.77, 135.90, 154.49, 159.93. TOF MS-ESþ, m/z: 632
[(M-Cl–)]þ, 710 f[(M-Cl–)]þ þ DMSOg. Anal. Calcd for C33H26Cl2N3PRuꢀ2.5H2O (%): C,
55.62; N, 5.90; H, 4.39. Found: C, 55.64; N, 5.99; H, 4.17.
Dichloro(40-(4-methylphenyl)-2,20:60,200-terpyridine)(triphenylphosphino)ruthenium
(II) (2). Complex 2 was synthesized in the same way as 1 using 40-(4-methylphenyl)-
2,20:60,200-terpyridine (64.67 mg, 0.2 mmol) and tris(triphenylphosphine)Ru(II)dichloride
(191.77 mg, 0.2 mmol). Yield: 109.86 mg (72.5%), red-brown solid. 1H NMR (400 MHz,
DMF-d7, ppm): d ¼ 9.36 (d, 2H); 8.67 (m, 2H); 8.51 (d, 2H); 8.41 (s, 2H); 7.94 (m, 9H);
7.58 (t, 2H); 7.43 (t, 6H); 2.47 (s, 3H). 31P NMR (400 MHz, DMF-d7, ppm): d ¼ 40.67. 13C
NMR (400 MHz, DMF-d7, ppm): d ¼ 20.51, 119.51, 122.31, 126.18, 127.35, 127.7, 129.05,
129.84, 132.37, 132.7, 132.96, 134.92, 135.7, 139.19, 143.25, 154.37, 159.86. TOF MS-
ESþ, m/z: 722 [(M-Cl–)]þ, 800 f[(M-Cl–)]þ
þ
DMSOg. Anal. Calcd for
C40H32Cl2N3PRuꢀ2H2O (%): C, 60.52; N, 5.29; H, 4.57. Found: C, 60.13; N, 5.29; H, 4.46.
Dichloro(triphenylphosphino)(4,40,400-tri-tert-butyl-2,20:60,200terpyridine)ruthenium
(II) (3). Complex 3 was synthesized in the same way as 1 using 4,40,400-tri-tert-butyl-
2,20:60,200-terpyridine (80.31 mg, 0.2 mmol) and tris(triphenylphosphine)Ru(II)dichloride
1
(191.77 mg, 0.2 mmol). Yield: 104.48 mg (62.5%), red solid. H NMR (400 MHz, DMF-d7,
ppm): d ¼ 9.16 (d, 2H); 8.85 (d, 2H); 8.24 (s, 2H); 7.52 (d, 9H); 7.28 (m, 3H); 7.14 (t, 2H);
1.38 (m, 27H). 31P NMR (400 MHz, DMF-d7, ppm): d ¼ 43.71. 13C NMR (400 MHz, DMF-
d7, ppm): d ¼ 29.47, 34.61, 119.30, 123.01, 127.61, 128.66, 132.83, 153.74, 155.69, 159.5,
165.03. TOF MS-ESþ, m/z: 835 (Mþ). Anal. Calcd for C45H50Cl2N3PRu (%): C, 64.66; N,
5.03; H, 6.03. Found: C, 64.51; N, 5.14; H, 6.33.
Dichloro(40-(4-chlorophenyl)-2,20:60,200-terpyridine)(triphenylphosphino)ruthenium
(II) (4). Complex 4 was synthesized in the same way as 1 using 40-(4-chlorophenyl)-
2,20:60,200-terpyridine (68.76 mg, 0.2 mmol) and tris(triphenylphosphine)Ru(II)dichloride
1
(191.77 mg, 0.2 mmol). Yield: 109.71 mg (70.5%), red solid. H NMR (400 MHz, DMF-d7,

JOURNAL OF COORDINATION CHEMISTRY
5
ppm): d ¼ 9.55 (d, 2H); 8.67 (d, 2H); 8.61 (s, 2H); 8.30 (d, 2H); 8.11 (m, 2H); 7.86 (t, 2H);
7.76 (t, 2H); 7.59 (m, 6H); 7.38 (m, 9H). 31P NMR (400 MHz, DMF-d7, ppm): d ¼ 40.29.
13C NMR (400 MHz, DMF-d7, ppm): d ¼ 119.79, 122.53, 126.44, 127.97, 129.34, 132.85,
134.62, 135.92, 136.82, 141.80, 154.52, 160.07. TOFMS-ESþ, m/z: 742 [Mþ], 820 [Mþ
DMSO]. Anal. Calcd for C39H29Cl3N3PRu (%): C, 60.20; N, 5.40; H, 3.76. Found: C, 59.90;
N, 5.31; H, 4.15.
þ
Dichloro(4-chloro-2,20:60,200-Terpyridine)(triphenylphosphino)ruthenium(II)
(5).
Complex 5 was synthesized in the same way as 1 using 4-chloro-2,20:60,200-terpyridine
(53.54 mg, 0.2 mmol) and tris(triphenylphosphine)Ru(II)dichloride (191.77 mg, 0.2 mmol).
1
Yield: 83.67 mg (59.6%), red solid. H NMR (400 MHz, DMF-d7, ppm): d ¼ 9.39 (d, 2H);
8.40 (d, 2H); 8.29 (s, 2H); 7.96 (t, 2H); 7.63 (t, 6H); 7.42 (m, 9H); 7.29 (m, 2H). 31P NMR
(400 MHz, DMF-d7, ppm): d ¼ 39.39. 13C NMR (400 MHz, DMF-d7, ppm): d ¼ 122.40,
126.80, 127.89, 132.91, 135.93, 137.06, 154.42, 158.74, 160.96. TOF MS-ESþ, m/z: 703
(Mþ). Anal. Calcd for C33H25Cl3N3PRu (%): C, 56.46; N, 5.99; H, 3.59. Found: C, 56.80; N,
6.33; H, 3.20.
Dichloro(2,6-bis(2-pyrazolyl)pyridine)(triphenylphosphino)ruthenium(II)
(6).
Complex 6 was synthesized in the same way as 1 using 2,6-bis(2-pyrazolyl)pyridine
(42.64 mg, 0.2 mmol) and tris(triphenylphosphine)Ru(II)dichloride (191.77 mg, 0.2 mmol).
Yield: 56.07 mg (43.3%), yellow solid. 1H NMR (400 MHz, DMF-d7, ppm): d ¼ 9.79 (d,
1H); 9.02 (m, 4H); 7.95 (m, 9H); 7.69 (m, 2H); 7.43 (m, 6H); 6.36 (m, 2H). 31P NMR
(400 MHz, DMF-d7, ppm): d ¼ 50.34. 13C NMR (400 MHz, DMF-d7, ppm): d ¼ 106.61,
110.33, 128.42, 130.13, 132.75, 137.51, 162.27. TOF MS-ESþ, m/z: 610 [(M-Cl–)]þ. Anal.
Calcd for C29H26Cl2N5PRu (%): C, 53.96; N, 10.85; H, 4.05. Found: C, 53.80; N, 10.84;
H, 3.90.
All the complexes gave 1H, 31P, and 13C NMR spectra corresponding to the pro-
posed structures and elemental analysis data consistent with their formulations. Mass
spectrometric data gave peaks corresponding to the masses of the complexes. The
NMR and MS spectra are placed in the Supporting Information (Figures S1–S24).
2.3. Instrumentation and measurements
NMR spectra were recorded on a Bruker Avance DPX 400 MHz Spectrophotometer at
303 K using Si(CH3)4 as a reference. Low resolution electron spray ionization (ESIþ)
mass spectra were recorded on the Waters Micromass LCT Premier Spectrometer or
Shimadzu LCMS 2020. Elemental analyses were done on a ThermoScientific Flash 2000
elemental analyser. Kinetic measurements for fast reactions were performed on an
Applied Photophysics SX20 Stopped Flow instrument coupled with an online data
acquisition system whose temperature is controlled within 0.1 ꢁC. The slow reactions
were monitored using a Varian Cary 100 Bio Ultraviolet-Visible Spectrophotometer
with an attached Varian Peltier temperature controller and online kinetic application.
The Ultraviolet-Visible Spectrophotometer was also used to pre-determine the wave-
lengths at which the reactions were monitored.

6
M. K. SITATI ET AL.
2.4. Kinetic measurements
The rate of substitution was measured under pseudo-first-order conditions. Kinetic sol-
utions were prepared by dissolving the required amount of complex in 0.1 M ionic
solution consisting of 0.01 M LiCl and 0.09 M NaClO4 in dry methanol to achieve a spe-
cific concentration. The chloride from LiCl suppressed any possibility of solvolysis of
the complexes. The perchlorate ion is a poor nucleophile and cannot competitively
substitute the co-labile ligand ahead of the incoming thiourea ligands [15].
Nucleophile stock solutions were prepared at 100 times higher than the concentration
of the respective complex and diluted to afford concentrations of 80, 60, 40, and 20
times. Equal volumes of nucleophile and metal compound solutions are mixed and
the change in absorbance with time of the solution mixture studied. The reaction
comes to an end when the absorbance no longer changes with time. The time taken
for absorbance versus time curve to flatten which is obtainable from the OriginPro 9.1
software gives the time the reaction takes to come to an end. The inverse of the
time(s) taken to complete a reaction gives the observed rate constant.
2.5. Computational modelling
Computations were done by Density Functional Theory (DFT) run on Gaussian 09 suite
of programs [16]. The structures were optimized using the hybrid Becke, 3-parameter,
Lee-Young-Parr method of Los Alamos National Laboratory 2 double f basis sets hav-
ing inner core electrons of the Ru replaced by relativistic effective core potential [17].
DFT applies to physically observable electron density over a wave function in deter-
mination of the properties of a system. Los Alamos National Laboratory 2 double f
basis set exploits relativistic effective core potentials to account for effect of inner core
28 electrons ([Ar]3d10) in Ru [18]. To take into account of the solvent effects, the com-
plexes were fully optimized in methanol using the conductor polarizable continuum
model [19]. The singlet state was used due to the low electronic spin state of the
Ru(II) complexes. The chemical potential (m) and molecular hardness (g) for each struc-
ture were calculated from the HOMO and LUMO energies. The global electrophilicity
indices (x) were determined by the relationship x ¼ m2/2g [20]. The charge on each
atom is expressed as natural bond orbitals (NBO) [21].
3. Results
3.1. Computational results
DFT calculated quantities (Table 1) have been used to explain kinetic behavior [22].
For example, electronic chemical potential, m, chemical hardness, g, and electrophilicity
index, x, have been used to support observed trends in the rates of substitution reac-
tions [23]. In this study, calculations and optimization were carried out to gain infor-
mation on the electronic and structural properties of the complexes. The DFT
optimized structures of the complexes are shown in Table 2 and a summary of
selected DFT results are presented in Table 1. The DFT calculated frontier molecular
orbitals (Table 2) show that the HOMO is located mainly on Ru and partially on the

JOURNAL OF COORDINATION CHEMISTRY
7
Table 1. Summary of DFT calculated data for the complexes investigated.
Parameters
1
2
3
4
5
6
Distances (Å)
Ru22-Cl23
Ru22-Cl25
Ru22-N39
Ru22-N40
2.58
2.56
1.97
2.10
2.10
2.59
2.55
1.97
2.10
2.10
2.59
2.56
1.97
2.10
2.10
2.59
2.48
1.97
2.10
2.10
2.57
2.55
1.96
2.10
2.10
2.56
2.56
1.99
2.10
2.10
Ru22-N41
Angles (ꢁ)
N41-Ru22-N40
N40-Ru22-N39
Cl23-Ru22-Cl25
NBO charges (eV)
Ru(22)
159.2
79.8
89.4
159.0
79.7
89.7
158.6
79.5
89.7
159.1
79.8
89.3
159.1
79.8
89.4
157.9
79.3
90.2
0.171
0.164
0.151
0.176
0.173
0.133
Orbital energy (eV)
HOMO
LUMO
–5.488
–2.479
3.009
–5.471
–2.514
2.957
–5.360
–2.289
3.070
–5.525
–2.568
2.957
–5.571
–2.604
2.967
–5.620
–2.180
3.440
DEHOMO-LUMO
Global chemical reactivity indices
g (eV)
m (eV)
x (eV)
1.504
–3.984
5.275
1.478
–3.992
5.389
1.535
–3.824
4.763
1.484
–4.088
5.633
1.478
–4.047
5.539
1.720
–3.900
4.422
g: chemical hardness; m: electronic chemical potential; x: electrophilicity index.
chloro ligands while the LUMO is on the N-N-N ligands as has also been observed
[24]. Figure 2 shows typical numbering of the atoms in the complexes.
The HOMO-LUMO energy gap has been used to predict kinetic stability and chem-
ical reactivity of the compounds. Compounds with wider energy gap (Table 1) are
likely to be kinetically stable and chemically less reactive [25]. The coordination geom-
etry about the Ru(II) in these complexes (Figure 1) is distorted octahedral. The angle
N40-Ru22-N39 (79.8ꢁ) and N41-Ru22-N40 (159.2ꢁ) is smaller than the expected 90ꢁ and
180ꢁ, respectively. The Cl23-Ru22-Cl25 angle is 90ꢁ confirming that the chloro groups
are cis. The DFT calculated results in Table 1 are in agreement with the literature find-
ings on similar Ru(II) complexes [26]. The DFT results reveal that the distances of the
axial nitrogens from Ru(II) (Ru22-N39) are shorter than those of the equatorial ones
(Ru22-N40/41). This further attests to the distortion in the coordination geometry of
the Ru(II) complexes.
3.2. Kinetic results
The rate of substitution of the chloro ligands was measured spectrophotometrically by
following the change in absorbance with time using an Ultraviolet-Visible
Spectrophotometer for slow reactions or a Stopped Flow spectrophotometer for fast
reactions. Spectral changes due to the reactions were observed from 200 to 800 nm to
establish a suitable wavelength at which the respective reaction for each metal com-
plex could be followed. All reactions were thermostated within
0.1 ꢁC of the set
value. The changes in absorbance accompanying the reactions were analyzed graphic-
ally using OriginPro 9.1 software. Kinetic traces were taken at appropriate wavelength
and fitted to a single exponential decay standard function to generate pseudo-first
order rate constants (kobs) using equation (1):
ð
Þ
At ¼ Ao þ ðAoꢂA Þ exp ꢂkobs
t
(1)
1

8
M. K. SITATI ET AL.
Table 2. DFT Minimum energy structures and frontier molecular orbitals of the complexes.
Optimized structures
HOMO
LUMO
1
2
3
4
5
6

JOURNAL OF COORDINATION CHEMISTRY
9
Figure 2. Structure of 1 illustrating numbering of atoms and the spatial orientation of the ligands
around the Ru(II) metal center.
Figure 3. Absorbance spectra for the reaction of 4 and DMTU on the UV visible spectrophotometer
at 298 K (inset is the kinetic trace obtained for the reaction at 317 nm).
where Ao ¼ absorbance at the commencement of the reaction, At ¼ absorbance at
time t, and A ¼ absorbance at the end of the reaction [15]. An example of such
1
spectral changes for the reaction of 4 with DMTU is shown in Figure 3.
The rate of nucleophilic attack by the thiourea nucleophiles was calculated from
the observed rate constant measured by varying the concentration of the nucleophile
at 25 ꢁC. The average values of the observed rate constant, kobs/obs , for the first or
0
0
second step of the reaction were plotted against [Nu]. Linear plots of kobs/obs versus
½
ꢃ
Nu were obtained for all reactions and typical plots are shown in Figure 4 for the
substitution reactions of 3 with the thiourea nucleophiles at 25 ꢁC.
0
The slopes represent the second order rate constants, k2 (a) and k2 (b), respectively.
Other similar plots are placed in Supporting Information (Figures S25, S26, S28, S29,
0
S31, S33, S34, and S36). Tables of kobs/obs and respective nucleophile concentrations
are presented in Supporting Information (Tables S1, S2, S5, S6, S9, S10, S17, and S18).
3.3. Confirmation of substitution mechanism by 31P NMR
The 31P NMR spectra in Figure 5 illustrate the substitution from 2 by the thiourea
nucleophile. The 31P NMR spectrum of 2 before reaction shows a single chemical shift

10
M. K. SITATI ET AL.
0
Figure 4. Plots of kobs (a) and kobs (b) vs. [Nu] for the reactions of 3 with the thiourea nucleo-
philes at 298 K.
Figure 5. 31P NMR spectral array for the reaction of 2 with thiourea (TU).
at 40.85 ppm. On mixing the complex with TU, a new peak at 34.2 ppm appears within
2 min with a concomitant disappearance of the 40.85 ppm resonance peak. The first
chloro substitution from 2 produced an intermediate coordinated with one chloro and
TU ligand. This intermediate reacts with another TU nucleophile at a much slower rate
as evidenced by a decrease in its resonance at 34.20 ppm and concomitant growing of
a resonance peak at 43.42 ppm after 32 min. This resonance is due to Ru(j3-
tptz)(PPh3)TU2 [27]. The 31P NMR peak characteristic of the free triphenylphosphine lig-
and (Figure 6) was not observed during the course of the substitution reaction.
Based on the kinetic data and 31P NMR kinetics analysis, the proposed mechanism
of chloro substitution in the complexes under investigation is represented in
Scheme 1.
The rate constants were also measured from 25 to 45 ꢁC in increments of 5 ꢁC.
0
Graphs of lnk2/2 /T versus 1=T were plotted in accordance with the Eyring equation.

JOURNAL OF COORDINATION CHEMISTRY
11
Figure 6. 31P NMR spectra for the free triphenylphosphine ligand.
Scheme 1. Proposed mechanisms of substitution of the chloro ligands from the Ru(II) complexes.
Typical Eyring plots are shown in Figure 7 for the reaction of 4 with the thiourea
nucleophiles.
Other Eyring plots are presented in Supporting Information Figures S27, S30, S32,
and S35. The tables of ln ðk2=TÞ and 1=T are provided in Supporting Information
¼
Tables S3, S4, S7, S8, S15, S16, and S19. The enthalpy of activation (DH ) and entropy
¼
of activation (DS ) were calculated from the slope and the intercept of the Eyring
¼
¼
0
0
plots, respectively. The rate constants (k2/2 ) and activation parameters (DH , DH ,
¼
¼
DS , and DS0 ) for the first and second substitution steps are summarized in Tables 3
and 4.
4. Discussion
The stepwise substitutions of the chloro ligands follow the order 3 > 4 > 5 > 2 >
1 > 6. The differences in the rate of substitution from all the complexes investigated
arise from the nature of substituents on the tpy backbone similar to what has been
reported for square planar Pt(II) complexes [28]. In analyzing the results, a clear under-
standing of the role the substituent(s) on tpy ligand is very important because it
changes the electronic properties of the ligand, thereby influencing the reactivity of
the Ru(II). Both p-back-bonding and r-trans effect have been found to control

12
M. K. SITATI ET AL.
Figure 7. Eyring plots for the reactions of 4 with the thiourea nucleophiles.
reactivity of tpy-Pt(II) complexes depending on the nature of the substituent(s)
attached on the tpy [28]. The r-trans-effect and p-back-bonding both alter the rate of
substitution in octahedral transition metal complexes [29].
Introduction of the electron-donating methylphenyl substituent [7] at the 40-pos-
ition of the tpy ligand in 1 to form 2 and addition of the strongly electron-donating
tert-butyl substituents [28] at the 40-trans and cis positions of 1 to form 3 results in
increased rate of substitution. The increase in the rate of substitution with the addition
of electron-donating substituents follows the order 1 < 2 < 3. The oxidation potentials
of these complexes increased as follows: 0.98 V (3) < 1.01 V (2) < 1.02 V (1) [30]. The
oxidation potentials inversely correlate to the electron-donating ability of the substitu-
ents on the ligands implying highest donation of electrons to Ru(II) in 3 [30].
The trend in the rate of substitution increases in the same way as the electron
donor strength, indicating that the reactivity is driven by r-trans-effect where electron
density donated to Ru(II) repels the electrons in the chloro ligand and thus weakening
the Ru-Cl bond resulting in increased reactivity. The strength of the trans-effect
increases from 1 to 3 in line with the trend in the reactivity. Evidence in support of
increase in electron donation going from 1 to 3 is further indicated by decrease in
DFT calculated NBO charges on the Ru metal center in the order 0.171 (1) > 0.164 (2)
> 0.151 (3), confirming that 3 is the least electrophilic. Further evidence of electron
donation in these complexes is seen in the raising of the HOMO energy as donor
effect increases (–5.488 (1) < ꢂ5.471 (2) < ꢂ5.360 (3)). It has been reported that
strong electron donors raise the HOMO energy [31–33]. The very high r-trans-effect in
3 results in unusually high reactivity compared to 1 and 2 which is due to donation of
electrons from both cis and trans positions. The trans-effect has been observed in a
number of studies [29].

JOURNAL OF COORDINATION CHEMISTRY
13
Table 3. Second order rate constants and activation parameters for the first substitution.
¼
¼
Complexes
Nu
k2 / (M–1 s–1
)
DH / (kJ mol–1
)
DS / (Jmol–1 K–1
)
TU
DMTU
TMTU
19.9 0.3
17.4 0.2
9.7 0.2
56
58
67
2
1
3
–27
–22
–3
5
2
7
1
2
TU
DMTU
TMTU
26.1 0.2
23.5 0.2
13.8 0.1
30
37
58
1
2
4
–116
–96
–31
3
5
9
TU
DMTU
TMTU
38.4 0.4
34.4 0.4
20.5 0.3
28
29
55
1
3
1
–121
–118
–34
4
7
2
3
4
TU
DMTU
TMTU
23.2 0.4
19.5 0.3
10.4 0.2
45
47
61
2
1
2
–68
–63
–29
6
4
5
TU
DMTU
TMTU
22.6 0.2
18.8 0.2
11.4 0.2
40
58
60
3
1
3
–85
–90
–40
7
3
7
5
6
TU
DMTU
TMTU
0.008 0.0003
0.007 0.0002
0.005 0.0003
80
90
120
2
3
1
–20
–15
–6
6
8
3
The addition of chlorophenyl and chloro ligands at the 40-position of the tpy ligand
in 1 forms 4 and 5, respectively, resulting in increase in reactivity as follows: 1 < 5 <
4. A chloro substituent withdraws electron density by p resonance [34] and this
enhances the p-back-donation of electron density from the Ru(II) orbitals into the p
anti-bonding molecular orbitals of the ligand. Consequently, the positive charge on
Ru(II) increases making it more attractive for nucleophilic attack. This observation is
supported by the increase in DFT-calculated NBO charges as follows: 0.171 (1) < 0.173
(5) < 0.176 (4). The electrophilicity indices also increase in the same manner (5.275 (1)
< 5.633 (4) < 5.539 (5)). This is an indication that 4 and 5 have enhanced p-back-

14
M. K. SITATI ET AL.
Table 4. Second order rate constants and activation parameters for the second substitution.
¼
¼
k2 / (10–1 M–1 –1
s
)
DH0 / (kJ mol–1
)
DS0 / (Jmol–1 K–1
)
0
Complexes
Nu
TU
DMTU
TMTU
108
23 0.4
2.5 0.2
2
62
78
118
1
2
1
–24
26
140
3
4
4
1
2
TU
DMTU
TMTU
166
64
6.5 0.1
3
2
36
74
106
3
3
3
–99
19
108
7
7
9
TU
DMTU
TMTU
195
171
22.4
4
2
1
34
49 0.3
98 0.2
2
–102
–58
89
5
1
1
3
4
TU
DMTU
TMTU
143
32 0.7
2.7 0.04
1
47
76 0.5
112
2
–59
24 1.2
121
7
2
5
TU
DMTU
TMTU
113
27 0.3
2.5 0.02
2
50
77
114 0.3
3
2
–56
25
130
7
5
1
5
6
TU
DMTU
TMTU
0.03 0.002
0.001 0.0001
0.0004 0.0001
92
110
129
2
3
2
–10
28
146
6
8
5
bonding which makes it easier for electron shift from the filled metal Ru d orbitals
ꢄ
into the empty ligand p -orbitals, hence higher reactivity compared to 1. The fact that
4 is more reactive than 5 indicates that the chlorophenyl substituent is a stronger
electron acceptor than the chloro ligand, in line with what has been observed [35].
Notably, 2 and 4 only differ in the substituent on the phenyl at the 40-position of
the tpy. Complex 2 has an overall electron-donating substituent (methyl substituent)
while 4 has electron-accepting substituent (chloro substituent). This is clearly sup-
ported by their respective DFT calculated quantities as already discussed. The higher
reactivity of 2 compared to 4 shows that trans-effect due to the methyl substituent in
2 in this study has a greater effect on the substitution reactions than the p-back-bond-
ing due to the chloro group in 4. The relative higher influence of trans-effect com-
pared to the p-back-bonding effect has been observed in other studies [36].

JOURNAL OF COORDINATION CHEMISTRY
15
The replacement of the cis positioned pyridyl ligands in 1 with pyrazolyl ligands
in 6 resulted in a sharp decrease in reactivity. The replacement of pyridyl ligands
lowers the p-back-bonding ability of the overall ligand system, leading to a less elec-
tropositive metal center and hence lower reactivity. As shown in the literature, pyra-
zole ligands are effective donors to transition metals [37]. Further, pyrazole has a
lower basicity (pKa ¼ 2.47) compared to pyridine (pKa ¼ 5.23) [38–40] which causes
it to bind metals more weakly than pyridine. The donor effect of the pyrazolyl
ligands is supported by the lower DFT calculated NBO charge for 6 (0.133) com-
pared to 1 (0.171), confirming that 1 is more electropositive. This is further corrobo-
rated by the higher electrophilicity index of 1 (5.275) compared to 6 (4.422). In
addition, the HOMO-LUMO energy gap and chemical hardness values for 1 are
smaller than those of 6 in support of the higher rate of substitution from 1. Further,
the LUMO of 6 (–2.180) is raised compared to that of 1 (–2.479), making it difficult
for p-back-donation. The higher p-back-bonding capabilities of the conjugated pyri-
dine rings in 1 readily accept electron density from the Ru(II) metal center compared
to the pyrazole rings that are p-electron rich due to an extra pyrollic-N within the
chelate ring and hence better p-donors [41].
0
The rate constants, k2 for substitution of the second chloro ligand for all the com-
plexes are lower than those of the first step, k2, due to decrease in the electrophilicity
of the metal center upon coordination of the first thiourea nucleophile in complexes
where p-back-bonding is dominant [42]. The reduction of the electrophilicity of Ru(II)
results from the donation of electrons by the incoming electron rich thiourea nucleo-
phile to the electron deficient metal center lowering its charge. Further, the coordi-
nated nucleophile introduces steric hindrance at the Ru(II) metal center, hindering the
approach of the second incoming nucleophile.
The first substitution occurs at the chloro ligand which is within the plane of the
tpy ligand framework, Cl23, followed by Cl25 which is perpendicular to the ligand
plane. The chloro ligand, Cl23, being within the plane of the ligand is most influenced
by the electronic changes of the tpy ligand. This is supported by DFT calculated bond
distances between the metal centers and the chloro ligands showing that Ru-Cl23
bonds are slightly longer than Ru-Cl25 by about 0.03 Å, hence easier to break. In add-
ition, since Cl25 is trans to a different type of ligand (triphenylphosphine) [43], the
rate of substitution of the chloro ligand varies for a given Ru(II) complex.
Generally, for both k2 and k20 the value of the activation enthalpy increases as the
bulkiness of the thiourea entering ligand increases, which must be related to the increas-
ing steric hindrance encountered by the entering ligand that increases the activation
enthalpy barrier. In terms of the activation entropy, there is a general trend of going
from more negative to more positive values on increasing the steric hindrance of the
entering thiourea nucleophile. This can be interpreted in terms of a steady changeover
from an associative interchange mechanism (Ia) to a more dissociative interchange (Id)
mechanism on increasing steric hindrance [44,45]. The trend in reactivity of the nucleo-
philes was TU > DMTU > TMTU. This can be accounted for in terms of steric factors
where reactivity decreases with increase in steric hindrance of the nucleophile.

16
M. K. SITATI ET AL.
5. Conclusion
The rate of substitutions in the current study are electronically driven either through
trans-effect or p-back-donation effects. The complex groupings 2, 3 and 4, 5 are more
reactive than 1 because of enhanced trans-effect and p-back-donation, respectively. The
reactivity of 4 is higher than 5 due to the presence of a chlorophenyl substituent on the
tpy ligand in 4 that is a stronger p-acceptor than the chloro ligand in 5. It has been
shown that the trans-effect in 2 influences the reactivity more strongly than the p-back-
donation in 4. The cis electron donation by 2,6-bis(pyrazolyl)pyridine ligand in 6 signifi-
cantly retards the reactivity of the Ru(II) compared to that of 1; hence, it can be used to
tune the reactivity of Ru(II) complexes. The reactivity of Ru(II) complexes is more strongly
affected by the electron-donating ligands (trans-effect) than ligands that enhance
p-back-donation. The tert-butyl substituents in 3 are very strong donor ligands whose
donation from both the cis and trans positions strongly accelerate the reactions. The
trend in the DFT calculated data supports the observed reactivity of the complexes.
There is a steady change in mechanism from an associative interchange mechanism (Ia)
to a more dissociative interchange (Id) mechanism on increasing steric hindrance.
Acknowledgments
We thank Mr. Craig Grimmer for his support with the NMR analysis, Mrs. Caryl Janse Van
Rensburg for her help with mass spectra and elemental analyses and Shaun Ball with manage-
ment of the deliveries.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This research was funded by the University of KwaZulu Natal South Africa.
ORCID
Deogratius Jaganyi
Allen Mambanda
http://orcid.org/0000-0003-4499-6877
http://orcid.org/0000-0002-8113-3643
References
[1] S. Sharma, S.K. Singh, D.S. Pandey. Inorg. Chem., 47, 1179 (2008).
[2] C. Metcalfe, S. Spey, H. Adams, J.A. Thomas. J. Chem. Soc., Dalton Trans., 4732 (2002).
[3] E.C. Constable. Adv. Inorg. Chem., 30, 69 (1986).
[4] L.X. Zhao, T.S. Kim, S.H. Ahn, T.H. Kim, E.K. Kim, W.J. Cho, H. Choi, C.S. Lee, J.A. Kim, T.C.
Jeong, C.J. Chang, E.S. Lee. Bioorg. Med. Chem. Lett., 11, 2659 (2001).
[5] K.K. Patel, E.A. Plummer, M. Darwish, A. Rodger, M.J. Hannon. J. Inorg. Biochem., 91, 220 (2002).
ꢀ
ꢀ
ꢀ
[6] P.M. van Vliet, S.M. Toekimin, J.G. Haasnoot, J. Reedijk, O. Novakova, O. Vrana, V. Brabec.
Inorg. Chim. Acta, 231, 57 (1995).
[7] A. Jain, C. Slebodnick, B.S. Winkel, K.J. Brewer. J. Inorg. Biochem., 102, 1854 (2008).
[8] Y. Liu, R. Hammitt, D.A. Lutterman, R.P. Thummel, C. Turro. Inorg. Chem., 46, 6011 (2007).

JOURNAL OF COORDINATION CHEMISTRY
17
[9] B.T. Farrer, H.H. Thorp. Inorg. Chem., 39, 44 (2000).
[10] N. Grover, N. Gupta, P. Singh, H.H. Thorp. Inorg. Chem., 31, 2014 (1992).
[11] C.W. Jiang, H. Chao, H. Li, L.N. Ji. J. Inorg. Biochem., 93, 247 (2003).
[12] H.Y. Ding, X.S. Wang, L.Q. Song, J.R. Chen, J.H. Yu, B.W. Zhang. J. Photochem. Photobiol. A,
177, 286 (2006).
[13] S. Sharma, M. Chandra, D.S. Pandey. Eur. J. Inorg. Chem., 2004, 3555 (2004).
[14] B.P. Sullivan, J.M. Calvert, T.J. Meyer. Inorg. Chem., 19, 1404 (1980).
[15] A. Shaira, D. Jaganyi. J. Coord. Chem., 67, 2843 (2014).
[16] M. Frisch, G. Trucks, H. Schlegel, G. Scuseria, M. Robb, J. Cheeseman, G. Scalmani, V.
Barone, B. Mennucci, G. Petersson. Gaussian 09, Revision D. 01, Gaussian, Inc., Wallingford,
CT (2009).
[17] P.J. Hay, W.R. Wadt. J. Chem. Phys., 82, 270 (1985).
[18] M. Okamura, M. Yoshida, R. Kuga, K. Sakai, M. Kondo, S. Masaoka. Dalton Trans., 41,
13081 (2012).
ꢀ
[19] T.L. Bahers, T. Pauporte, G. Scalmani, C. Adamo, I. Ciofini. Phys. Chem. Chem. Phys., 11,
11276 (2009).
[20] P.K.; Chattaraj, U.; Sarkar, M.; Elango, R.; Parthasarathi, V.; Subramanian. J. Chem. Sci., 117,
599 (2005).
[21] OriginLab Corporation. OriginPro 9.1. OriginLab Corporation, Northampton, MA (2018).
[22] R.G. Parr, W. Yang. In Density-Functional Theory of Atoms and Molecules, Vol. 16,
International Series of Monographs on Chemistry, Oxford University Press, New York (1989).
[23] R.G. Parr, W. Yang. J. Am. Chem. Soc., 106, 4049 (1984).
[24] S. Sangilipandi, D. Sutradhar, K. Bhattacharjee, W. Kaminsky, S.R. Joshi, A.K. Chandra, K.M.
Rao. Inorg. Chim. Acta, 441, 95 (2016).
[25] S.B. Jensen, S.J. Rodger, M.D. Spicer. J. Organomet. Chem., 556, 151 (1998).
[26] S.B. Billings, M.T. Mock, K. Wiacek, M.B. Turner, W.S. Kassel, K.J. Takeuchi, A.L. Rheingold,
W.J. Boyko, C.A. Bessel. Inorg. Chim. Acta, 355, 103 (2003).
[27] T. Ben-Hadda, C. Mountassir, H.L. Bozec. Polyhedron, 14, 953 (1995).
[28] D. Reddy, K.J. Akerman, M.P. Akerman, D. Jaganyi. Transition Met. Chem., 36, 593 (2011).
[29] B.J. Coe, S.J. Glenwright. Coord. Chem. Rev., 203, 5 (2000).
[30] A. Jain, J. Wang, E.R. Mashack, B.S.J. Winkel, K.J. Brewer. Inorg. Chem., 48, 9077 (2009).
[31] G.K. Mutua, D.O. Onunga, M. Sitati, D. Jaganyi, A. Mambanda. Inorg. Chim. Acta, 514,
119972 (2021).
[32] M. Maestri, N. Armaroli, V. Balzani, E.C. Constable, A.M.W.C. Thompson. Inorg. Chem., 34,
2759 (1995).
[33] C.A. Mebi. J. Chem. Sci., 123, 727 (2011).
[34] D. Reddy, D. Jaganyi. Dalton Trans., 6724, 6724 (2008).
ꢁ
ꢀ
ꢀ
ꢀ
ꢁ
ꢀ
[35] M.M. Milutinovic, A. Rilak, I. Bratsos, O. Klisuric, M. Vranes, N. Gligorijevic, S. Radulovic, ZD.
ꢁ ꢀ
Bugarcic. J. Inorg. Biochem., 169, 1 (2017).
[36] E. Shustorovich, M. Porai-Koshits, Y.A. Buslaev. Coord. Chem. Rev., 17, 1 (1975).
[37] D.L. Jameson, J.K. Blaho, K.T. Kruger, K.A. Goldsby. Inorg. Chem., 28, 4312 (1989).
[38] J. Catalan, J. Elguero. In Advances in Heterocyclic Chemistry, A.R. Katritzky (Ed.),
pp. 187–274, Academic Press, Orlando (1987).
[39] C. Wijnberger, C.L. Habraken. J. Heterocycl. Chem., 6, 545 (1969).
[40] D.L. Jameson, K.A. Goldsby. J. Org. Chem., 55, 4992 (1990).
[41] J.M. Holland, J.A. McAllister, C.A. Kilner, M. Thornton-Pett, A.J. Bridgeman, M.A. Halcrow. J.
Chem. Soc., Dalton Trans., 548 (2002).
[42] B.B. Khusi, A. Mambanda, D. Jaganyi. J. Coord. Chem., 69, 2121 (2016).
[43] T. Karlen, P. Dani, D.M. Grove, P. Steenwinkel, G. van Koten. Organometallics, 15, 5687
(1996).
[44] H.K. Mandal, P.K. Ghosh, A. Mahapatra. Polyhedron, 29, 2867 (2010).
[45] G.K. Mutua, R. Bellam, D. Jaganyi, A. Mambanda. J. Coord. Chem., 72, 2931 (2019).