In this contribution we advance and explore the thermally induced hopping (TIH) mechanism for long-range charge transport (CT) in DNA and in large-scale chemical systems. TIH occurs in donor-bridge-acceptor systems, which are characterized by off-resonance donor-bridge interactions (energy gap DeltaE > 0), involving thermally activated donor-bridge charge injection followed by intrabridge charge hopping, We observe a "transition" from superexchange to TIH with increasing the bridge length (i.e., the number N of the bridge constituents), which is manifested by crossing from the exponential N-dependent donor-acceptor CT rate at low N (< N-x) to a weakly (algebraic) N-dependent CT rate at high N (>N-X). The "critical" bridge size N-X is determined by the energy gap. the nearest-neighbor electronic couplings. and the temperature. Experimental evidence for the TIH mechanism was inferred from our analysis of the chemical yields for the distal/proximal guanine (G) triplets in the (GGG)+TTXTT(GGG) duplex (X = G, azadine ((z)A), and adenine (A)) studied by Nakatani, Dohno and Saito [J. Am. Chem. Soc. 2000, 122, 5893]. The TIH sequential model, which involves hole hopping between (GGG) and X, is analyzed in terms of a sequential process in conjunction with parallel reactions of (GGG)(+) with water, and provides a scale of (free) energy gaps (relative to (GGG)) of A = 0.21-0.24 eV for X = A, Delta = 0.10-0.14 eV for X = (z)A, and Delta = 0.05-0.10 eV for X = G. We further investigated the chemical yields for long-range TIH in (G)(l)X-+(n)(G)(l) (l = 1-3) duplexes, establishing the energetic constraints (i.e., the donor (G)(l)(+)-bridge base (X) energy gap Delta), the bridge structural constraints (i.e., the intrabridge X-X hopping rates k(m)), and the kinetic constraints (i.e., the rate k(d) for the reaction of (G)(l)(+) with water). Effective TIH is expected to prevail for Delta less than or similar to 0.20 eV with a "fast" water reaction (k(d)/k(m) similar or equal to 10(-3)) and for Delta < 0.30 eV with a "slow" water reaction (k(d)/k(m) similar or equal to 10(-5)). We conclude that (T)(n) bridges (for which Delta similar or equal to 0.6 eV) cannot act in TIH of holes. From an analysis based on the energetics of the electronic coupling matrix elements in G(+)(T-A)(n)(GGG) duplexes we conclude that the superexchange mechanism is expected to dominate for n = 1-4. For long (A)(n) bridges (n greater than or similar to 4) the TIH prevails. provided that the water side reaction is slow, raising the issue of chemical control of TIH through long (A)(n) bridges in DNA attained by changing the solution composition.